CD counts: \r\n* For Stratum : CD+ cell count greater than  cells/mm^ obtained within  weeks prior to enrollment at any United States (U.S.) laboratory that has a clinical laboratory improvement amendments (CLIA) certification or its equivalent\r\n* For Stratum : CD cell count between - cells/mm^ obtained within  weeks prior to enrollment at any U.S. laboratory that has a clinical laboratory improvement amendments (CLIA) certification or its equivalent\r\n* Expansion Cohort: CD cell count for this cohort will be specified once Stratum  and Stratum  have completed enrollment\r\n* Solid Tumor Expansion Cohort: CD+ cell count greater than  cells/mm^ obtained within  weeks prior to enrollment at any U.S. laboratory that has a clinical laboratory improvement amendments (CLIA) certification or its equivalent\r\n* cHL Cohort: CD cell count of at least  cells/mm^
Presence of BRAFVE in tumor tissue as previously determined by a local assay at any time prior to Screening or by the central laboratory
For patients enrolled via local molecular testing, an archival or fresh tumor tissue (unless medically contraindicated) is required to be submitted for independent central molecular testing at Ignyta's CLIA laboratory post-enrollment
Other baseline laboratory evaluations, listed in Section ., must be done within  days prior to randomization.
Patient must have TCCs tumors harboring a TSC or TSC mutation identified by a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory
Previously registered to A, with the result of lung cancer harboring an EGFR exon  deletion or LR mutation; the testing must have been performed by one of the following criteria:\r\na) Patient registered to A and the assessment performed centrally by the protocol-specified laboratory\r\nb) By a local Clinical Laboratory Improvement Amendments (CLIA) certified laboratory; the report must indicate the result as well as the CLIA number of the laboratory that performed the assay; these patients will also have been registered to A, but can be enrolled on A regardless of the central lab results\r\n* Patients with known resistant mutations in the EGFR tyrosine-kinase (TK) domain (TM) are not eligible\r\n* Patients that are both EGFR mutant and anaplastic lymphoma kinase (ALK) rearrangements will be registered to A
Tumors must be tested and known negative for EGFR tyrosine kinase inhibitor (TKI) sensitizing mutations (EGFR exon  deletions, LR, LQ, GX) and ALK gene rearrangements by routine Clinical Laboratory Improvement Act (CLIA)-certified clinical testing methods; negative circulating tumor DNA results alone are not acceptable; prior testing for tumor PD-L status is not required
Tissue must have been determined to have local p/q co-deletion and IDH mutation prior to submission for central path review\r\n* Tumor tissue must show co-deletion of chromosomes p and q; for eligibility, the p/q analysis results will be accepted from the local site, as determined by either a locally available or reference laboratory (for US, must be Clinical Laboratory Improvement Act [CLIA] certified); acceptable methods for determination of p/q loss include fluorescent in-situ hybridization (FISH), by genomic sequencing or methylomic analyses; US and Canadian sites must send a copy of the official report to the pathology coordinator and quality assurance specialist (QAS)\r\n* Tumor must also show evidence of IDH mutation by immunohistochemistry or genomic analyses; this should be performed at the local site (US: performed in a CLIA certified laboratory); the site must send a copy of the official report to the pathology coordinator and QAS
Histologically confirmed UC of the bladder, urethra, ureter or renal pelvis with positive retinoblastoma (Rb+)/CDKNA- based on immunohistochemistry (IHC) of tissue blocks or unstained slides performed within a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory at University of North Carolina (UNC); if stage I of original cohort indicates futility, molecular requirement for eligibility will change to Rb+/CCND overexpression (also based on IHC)
Pretreatment cytogenetics must be performed on all patients; collection of pretreatment specimens must be completed within  days prior to registration to S; specimens must be submitted to the site's preferred Clinical Laboratory Improvement Amendments (CLIA)-approved cytogenetics laboratory; reports of the results must be submitted as described; note that cytogenetics are required at other time points
Formalin fixed paraffin embedded tumor tissue (preferably from the most recent recurrence) must be available to assess Rb protein status prior to enrollment on phase I or surgical study; if the subject has results from prior Rb IHC testing in a Clinical Laboratory Improvement Act (CLIA)-certified laboratory the requirement for screening to assess Rb protein status is waived; in these cases, patients will not be required to sign a screening consent
Patients with recurrent diffuse intrinsic brain stem glioma (DIPG) that has an atypical presentation must also submit the tumor tissue for Rb protein status confirmation or provide previous testing results from a CLIA certified laboratory; patients who have been biopsied for atypical DIPG but do not have sufficient tissue for Rb screening are not eligible
PHASE I (STRATUM ): Patient has intact Rb protein confirmed either from previous results or screened tissue; all testing must be performed in a CLIA certified laboratory; DIPG patients with radiographically typical appearance will be waived from this requirement
All patients with breast and gastric/gastroesophageal junction cancers should have HER testing performed using a FDA approved test in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory.
Pathologically confirmed recurrent or metastatic advanced solid tumor, for which there is no curative-intent treatment option and confirmation of the presence of AKT, AKT, or AKT mutations detected by the Memorial Sloan-Kettering (MSK)-integrated mutation profiling of actionable cancer targets (IMPACT) assay platform or other Clinical Laboratory Improvement Act (CLIA)-approved test
HER positive patients by local laboratory testing.
Presence of alteration in CDK pathway (amplifications in CDK, CDK, CCND, CCND, CCND or CCNE or loss of CDKNA) using a Clinical Laboratory Improvement Act (CLIA)-certified assay
Molecular testing results from Clinical Laboratory Improvement Amendments (CLIA)-certified laboratories used for patient eligibility should be obtained from the most recent tumor biopsy (baseline tumor biopsies and on-progression tumor biopsies are optional)
Participants must have histologically confirmed advanced malignancy that is metastatic and/or unresectable and/or recurrent with confirmed inactivating mutations in TSC or TSC or activating MTOR mutations, identified in any Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory; all genetic findings must be reviewed by the study principal investigator (PI), Dr. David Kwiatkowski, prior to study entry
Uric acid if elevated, corrected to within laboratory range prior to dosing
Molecular confirmation of a RET translocation is required to begin protocol therapy; methods of acceptable molecular confirmation include RET fluorescent in situ hybridization (FISH) and next-generation sequencing performed in a Clinical Laboratory Improvement Amendment (CLIA) certified lab
Uric acid must be within laboratory normal range
For enrollment to arm : participants must have a confirmed CCND, , or  high-level amplification, CCND mutation, or a CCND splice variant expected to lead to nuclear retention of cyclin D protein, via Dana-Farber Cancer Institute (DFCI)/Brigham and Women's Hospital (BWH) OncoPanel or any Clinical Laboratory Improvement Act (CLIA)-certified method
Able to provide a sufficient amount of representative tumor specimen for central laboratory testing of RAS mutation status and microsatellite stable (MSS).
RAS mutation per local assay at any time prior to Screening or by the central laboratory.
MYD and CXCR mutated disease (determined by Treon laboratory or molecular diagnostics laboratory)
ENROLLMENT TO THE DOSE ESCALATION, EXPANSION AND PART II: Participants must have histologically confirmed advanced NSCLC (with a confirmed KRAS mutation via any Clinical Laboratory Improvement Act [CLIA]-certified method) for which curable treatment modalities are not an option
Adequate laboratory results including the following:
Histologic proof of melanoma reviewed and confirmed by the treating institution; the melanoma must have a documented BRAF VE or BRAF VK mutation by genotyping or immunohistochemistry (IHC)  performed by a Clinical Laboratory Improvement Act (CLIA) certified laboratory; at Memorial Sloan-Kettering (MSK), the diagnostic molecular pathology laboratory has developed and implemented a targeted capture-based next-generation deoxyribonucleic acid (DNA) sequencing assay, MSK-integrated mutation profiling of actionable cancer targets (IMPACT), to profile all protein-coding exons and selected introns from  oncogenes and tumor suppressor genes in formalin-fixed paraffin embedded tissues; MSK-IMPACT has been approved by the New York (NY) State Department of Health to be run as a clinical assay in the CLIA-compliant diagnostic molecular pathology laboratory; MSK-IMPACT is capable of detecting mutations, copy number alterations, and structural variations; BRAF exon was captured by the MSK-IMPACT panel and the c.T>A (p.VE) mutation was fully validated as per New York State (NYS) requirements; detailed results of the validation of this mutation were included in the validation package submitted to NY State Department of Health
Molecular testing results from clinical laboratory improvement amendments (CLIA)-certified laboratories (using tissue and/or blood) demonstrating HER overexpression or amplification. Participants must have one of the following tumor types: biliary cancer, salivary cancer, or bladder cancer. a) For participants screened using a blood assay: obtain tissue-based testing result confirming study eligibility (within first  weeks after enrollment)
Molecular testing results from CLIA-certified laboratories (using tissue and/or blood) demonstrating EGFR-activating mutations Vemurafenib plus Cobimetinib
Molecular testing results from CLIA-certified laboratories (using tissue and/or blood) demonstrating BRAF V mutations a) For participants screened using a blood assay: obtain tissue-based testing result confirming study eligibility (within first  weeks after enrolment) Vismodegib
Molecular testing results from CLIA-certified laboratories (using tissue and/or blood) demonstrating hedgehog pathway relevant mutation (activating mutation of smoothened [SMO] or loss-of-function mutation of protein patched homolog- [PTCH-]) a) For participants screened using a blood assay: obtain tissue-based testing result confirming study eligibility (within first  weeks after enrollment)
Molecular testing results from CLIA-certified laboratories (using tissue) demonstrating programmed death-ligand  (PD-L) copy number gain/amplification, deficiency in mismatch repair enzymes (dMMR), high levels of microsatellite instability (MSI-H) or elevated tumor mutational burden (TMB >= mutations/ MB).
All therapy should be dispensed at the primary institution; we encourage all imaging studies to be reviewed and reported by the primary institution; laboratory studies may be performed at a Clinical Laboratory Improvement Act (CLIA)-certified laboratory of the investigators choice
Patients with histologically confirmed diagnosis of a primary central nervous system tumor will be eligible; patient tumors must test positive for the BRAFVE or the BRAF Ins T mutation at a Clinical Laboratory Improvement Act (CLIA)-approved laboratory; if either mutation cannot be confirmed from a prior test and archival tumor is not available to confirm presence of either mutation, patients must have tumor biopsy to collect tumor sample for mutation confirmation
Patient has adequate biological parameters as demonstrated by the following blood counts at baseline (obtained <  days prior to randomization; laboratory testing performed as part of standard of care prior to patient signature of informed consent for the study will be acceptable as baseline laboratory work as long as testing is performed <  days prior to randomization):
Patient has the following blood chemistry levels at baseline (obtained <  days prior to randomization; laboratory testing performed as part of standard of care prior to patient signature of informed consent for the study will be acceptable as baseline laboratory work as long as testing is performed <  days prior to randomization):
Patient has no clinically significant abnormalities on urinalysis results (obtained <  days prior to randomization; laboratory testing performed as part of standard of care prior to patient signature of informed consent for the study will be acceptable as baseline laboratory work as long as testing is performed <  days prior to randomization).
Stratum A: Newly diagnosed children (- years old) with DIPG who are positive for the H.KM mutation (positive testing in Clinical Laboratory Improvement Act [CLIA] laboratory) that underwent standard radiation therapy
Stratum B: Newly diagnosed children (- years old) with diagnosis of glioma other than DIPG who are positive for the H.KM mutation (positive testing in CLIA laboratory) including spinal cord gliomas that underwent standard radiation therapy
Participants enrolling into the MET cohort must have a MET exon  mutation as confirmed by targeted next generation (NextGen) sequencing using the Dana-Farber Cancer Institute (DFCI)/Brigham and Womens Hospital (BWH) OncoPanel or another Clinical Laboratory Improvement Act (CLIA)-certified method; participants whose NSCLC specimens contain actionable genetic mutations/alterations (e.g. ALK/EGFR) should receive appropriate targeted therapies prior to enrollment in the trial
PROCUREMENT INCLUSION: CD positive tumor as assayed in a Clinical Laboratory Improvement Act (CLIA) certified pathology laboratory (result can be pending at this time)
TREATMENT INCLUSION: CD-positive tumor as assayed in a CLIA certified pathology laboratory
Participants must have one of the following (confirmed via targeted NextGen Sequencing using the DFCI/BWH OncoPanel or another Clinical Laboratory Improvement Act [CLIA]-certified method):\r\n* For the replicative stress cohort: MYC amplification, CCNE amplification, Rb loss, FBXW mutation, or another genomic abnormality indicative of replicative stress as agreed upon with the principal investigator -OR-\r\n* For the HR deficiency cohort: genomic or somatic mutation in BRCA, BRCA, PALB, RADC, RADD, ATR, ATM, CHK, the Fanconi anemia pathway genes, or another genomic or somatic mutation in a known HR gene as agreed upon with the principal investigator.\r\n* For enrollment to the CCNE cohort: CCNE amplification of -fold or greater. Patients with borderline amplification levels may be considered following approval from the overall principal investigator.
Tumor positive for EBV encoded RNA (EBER) based on report from certified laboratory.
Acceptable laboratory results
Patients must have available tumor molecular profiling from Clinical Laboratory Improvement Amendments (CLIA)-certified labs or have available archived tissue to be sent to such a laboratory in the context of this investigation
Molecular testing in a CLIA-certified laboratory must have demonstrated a deletion involving the CDKNA locus or a mutation within the locus that can be deemed from best available evidence to be likely to cause inactivation of a gene within or protein encoded by CDKNA; sequencing or fluorescence in situ hybridization (FISH)/chromogenic in situ hybridization (CISH) methods are acceptable; the investigators will consider analyses performed according to similar standards as applied by Foundation Medicine (likely to be the most common source of molecular diagnostic data for patients in this trial)
Laboratory requirements:
INCLUSION CRITERIA FOR STRATUM C: Diagnosis of hypermutated brain tumors\r\nPatients with brain tumors and increased tumor mutation burden as determined by\r\n* Confirmed diagnosis of CMMRD syndrome by Clinical Laboratory Improvement Act (CLIA)-certified germline gene sequencing OR\r\n* Confirmation of high mutation burden by whole genome/exome sequencing performed in a CLIA-certified laboratory and/or the use of Foundation One next generation sequence panel or another CLIA approved targeted sequencing lab with publicly available correlations between number of mutations found in the panel and mutations per megabase and/or genome; for protocol purposes a high mutation burden will be defined as at least  non-synonymous coding-region mutations by whole exome/genome sequencing (well above two standard deviations of the number of median similar mutations described in pediatric CNS cancers) AND/OR a high tumor mutation burden (TMB) or intermediate TMB based on the reporting parameters of the panel; TMB parameters provided for the Foundation One reports are high tumor mutation burden is >=  mutations per megabase or intermediate TMB is between  to  mutations per megabase\r\n* Confirmed diagnosis of Lynch syndrome by CLIA-certified germline gene sequencing; patients with Lynch syndrome will not be accounted for in primary objective unless their tumors are determined to have the minimum number of mutations described above but they will still be eligible for this study\r\n* Low-grade tumors in patients with CMMRD or Lynch syndrome do not have to reach the threshold of  mutations for study inclusion
A documented deleterious gBRCA/m obtained in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory, including but not limited to Myriad Genetics, either by multi-gene panels or individual testing, for cohort  patients prior to study enrollment; variants of uncertain significance (VUS) of BRCA/ are not considered deleterious; patients with VUS or deleterious mutation in other genes without gBRCA/m can be considered for cohort  or  or 
Patients must have tumor evidence of somatic genomic molecular alteration in EGFR, HER, ERBB, or ERBB, from a test result generated in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory; the tumor tissue sample used to generate the qualifying report must be from a muscle-invasive or higher stage urinary tract cancer specimen (metastatic tissue is also acceptable); final determination about whether a specific tissue source or molecular genomic finding meets criteria as a qualifying result rests with the central study principal investigator (PI)
Methylation CHFR gene promoter in archival tissue biopsy\r\n* A patient will be considered to have CHFR methylation if he/she has a methylation specific band on methylation-specific PCR (MSP) for the CHFR gene or lack of expression by IHCs; MSP primers are publicly reported and developed at Oncomethylome in a Clinical Laboratory Improvement Amendments (CLIA) laboratory; patients who test positive for MSI at any of the  loci will be considered MSI+ as per standard convention or who have absent expression of mutL homolog  (MLH), mutS homolog  (MSH), mutS homolog  (MSH), or PMS postmeiotic segregation increased  (PMS) by IHC\r\n* Results from another institutions CLIA-certified MSI/IHC will be considered for eligibility\r\n* Patients with microsatellite instability and a family history supportive for a possible diagnosis of hereditary nonpolyposis colorectal cancer will be referred to a genetics counselor for further evaluation and recommendations
PHYSICAL AND LABORATORY TEST FINDINGS
Hemoglobin <  g/dL. Qualifying laboratory value must occur at most recent measurement before enrollment and must be no more than  days before enrollment. No transfusions are allowed within  hours before qualifying laboratory value
Known mutation of the IDH or IDH genes in the tumor\r\n* Documentation that no IDH or IDH mutations are present in the tumor by a Clinical Laboratory Improvement Amendments (CLIA) approved laboratory is required prior to initiation of study treatment
Participants must have a genomic (DNA and/or ribonucleic acid [RNA]) alteration (mutation, fusion, and/or amplification) involving PDGF-A, PDGF-B, PDGFR-A, PDGFR-B, FGF, FGF, FGFR or FGFR, as identified by tumor (formalin-fixed, paraffin-embedded [FFPE] or fresh, diagnosis or relapse tissue, but relapse tissue preferred) sequencing; sequencing will be performed through the University of Michigan MI-ONCOSEQ study (Clinical Laboratory Improvement Act [CLIA]-certified), or other (non-university [U] of Michigan) CLIA-certified tumor DNA or RNA sequencing
Adequate laboratory results including the following:
Consent to MD Anderson companion laboratory protocol -.
Patients must meet at least one of the following AVPC criteria: \r\n* Histologically proven small cell (neuroendocrine) prostate carcinoma.\r\n* Exclusive visceral metastases. \r\n* Predominantly lytic bone metastases identified by plain x-ray or CT scan. \r\n* Bulky (>=  cm in longest dimension) lymphadenopathy or high-grade tumor mass in prostate/pelvis. \r\n* Low PSA (=<  ng/mL) at initial presentation (prior to androgen ablation or at symptomatic progression in the castrate-setting) plus high volume (>= ) bone metastases. \r\n* Elevated serum lactate dehydrogenase (>= x upper limit of normal) or elevated serum carcinoembryonic antigen (>=  x upper limit of normal) in the absence of other etiologies. \r\n* Short interval (=<  days) to castrate-resistant progression following initiation of hormonal therapy. \r\n* Known loss or mutation (by Clinical Laboratory Improvement Act [CLIIA] certified molecular testing, immunohistochemistry staining method [IHC] and/or DNA sequencing) in at least  of the following: Tp, RB and PTEN.
Documented non-synonymous somatic mutation in NF in any tumor specimen or cell-free DNA assay by Clinical Laboratory Improvement Act (CLIA)-approved laboratory
PTEN or PIKCB mutated advanced solid tumor\r\n* PTEN loss of function mutation or PIKCB gain of function mutation identified by local Clinical Laboratory Improvement Act (CLIA) certified next generation sequencing (NGS)\r\n* Breast cancers patients enrolled on this study must have either:\r\n** Estrogen receptor positive and HER negative breast cancer\r\n** Triple negative breast cancer
Patients must have vulvar HSIL as confirmed by pathology report from a Clinical Laboratory Improvement Act (CLIA)-certified laboratory
Measurable metastatic or unresectable malignancy expressing GV mutated KRAS as assessed by one of the following methods: reverse transcriptase-polymerase chain reaction (RT-PCR) on tumor tissue, tumor deoxyribonucleic acid (DNA) sequencing or any other Clinical Laboratory Improvement Act (CLIA) certified laboratory test on resected tissue; patients shown to have tumors expressing GV mutated NRAS and HRAS will also be eligible
Consent to MD Anderson laboratory protocol PA-.
Have one of the following confirmed histologically, cytologically, or through biochemical testing:\r\n* Wild-type GIST (GIST without KIT or PDGFRA mutation);\r\n* PHEO/PGL with a germline mutation in SDHA, SDHB, SDHC, or SDHD;\r\n* Renal cell cancer associated with HLRCC\r\n* Testing will be performed in Clinical Laboratory Improvement Act (CLIA) certified labs using genetic tests for KIT/PDGFRA and testing panels developed for patients with PHEO/PGL; results from outside labs will be accepted; pathologic diagnosis will be reviewed and verified at the Clinical Center
Patients must have histologically confirmed adenocarcinoma of the colon that has metastasized (stage ) and is TP mutant/deleted by a Clinical Laboratory Improvement Act (CLIA) approved genetic test; only known loss of function TP mutation/deletion will be eligible for this study
Patients must have a diagnosis of CLL/SLL and EITHER have high-risk cytogenetic features or molecular features, defined as: del(p), del(q), mutated TP, complex metaphase karyotype (defined as >= unrelated chromosomal abnormalities, present in at least  metaphases on conventional, stimulated cytogenetic analysis) OR have developed a BTK or PLCG mutation, detected by sequencing and have not developed disease progression during ibrutinib therapy as defined by International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria OR BM has not normalized after at least  year (yr) on ibrutinib therapy\r\n* Note: some patients treated with ibrutinib may no longer have detectable fluorescence in situ hybridization (FISH), karyotypic or molecular abnormalities after  months of therapy. These patients will be eligible if they fulfill the above criteria on a bone marrow biopsy or peripheral blood specimen taken within the  months prior to starting ibrutinib or at some time during their ibrutinib therapy and analyzed at a Clinical Laboratory Improvement Act (CLIA)-accredited laboratory
Must have either a clinical diagnosis of NF or a germline NF mutation, or in patients without the NF syndrome, demonstrate an NF mutation in the GIST verified in a Clinical Laboratory Improvement Act (CLIA) certified laboratory; in patients without the NF syndrome, confirmation of the NF mutation in the GIST is required for enrollment
Patients must have a histologically or cytologically confirmed measurable GIST without platelet-derived growth factor receptor, alpha polypeptide (PDGFRA) or KIT proto-oncogene receptor tyrosine kinase (KIT) mutations; GIST may be newly diagnosed or recurrent provided that it meets criteria for progressive or metastatic disease; metastatic disease refers to disease outside the gastrointestinal (GI) tract, not simply a multifocal primary tumor; testing performed by the Laboratory of Pathology, National Cancer Institute (NCI), unless previously conducted by a CLIA/College of American Pathologists (CAP) external laboratory; analysis will include evaluation of  exons of KIT (, , , ) and  exons of PDGFRA (, , )
Molecular identification of a KRAS mutation (codons , , or  mutations detected by sequencing) by a Clinical Laboratory Improvement Amendments (CLIA)-certified assay (source documentation required)
Documented ALK-rearrangement (or ROS rearrangement for phase I only) break-apart fluorescence in situ hybridization (FISH) (in >= % or tumor cells), or next generation sequencing assay performed on tumor sample or cell-free DNA in Clinical Laboratory Improvement Amendments (CLIA)-approved laboratory
Laboratory requirements:
Have all of the following results as part of screening laboratory assessments (results from either the central laboratory or a local laboratory can be used for qualification):
Previously obtained tumor sample exhibits a hypermutator phenotype; for the purposes of this trial, a hypermutator phenotype is defined as tumors harboring >=  mutations (non-synonymous somatic point or indel mutations) detected by the Memorial Sloan Kettering (MSK)-Integrated Mutation Profiling for Actionable Cancer Targets (IMPACT) or comparable next generation sequencing performed in a Clinical Laboratory Improvement Act (CLIA) environment; contingent to approval by the MSK principal investigator, patients with less than  mutations may be eligible if they display a mutation in a mismatch repair gene or other mutations in genes known to be associated with hypermutator phenotypes or microsatellite instability, including but not limited to MutL homolog (MLH), MutS protein homolog (MSH), MSH, PMS postmeiotic segregation increased  (S. cerevisiae) (PMS), polymerase (deoxyribonucleic acid [DNA] directed), epsilon- (POLE), polymerase (DNA directed), delta , catalytic subunit (POLD) as determined by validated methods, or if microsatellite instability is present, as identified by polymerase chain reaction (PCR) or other validated methods\r\n* Note: the MSK-IMPACT (Integrated Mutation Profiling for Actionable Cancer Targets) assay is a next generation genomic profiling performed on formalin-fixed, paraffin-embedded (FFPE) tumor tissue in a CLIA-certified Molecular Diagnostic Service laboratory; IMPACT provides full exon coverage of  cancer related genes and can detect base substitutions, small indels, copy number alterations and selected gene re-rearrangements; in some cases, additional assays such as Sanger sequencing or fluorescence in situ hybridization (FISH) may be required to confirm specific results detected on IMPACT; patients at MSK will have this assay to determine eligibility; use of other validated next-generation sequencing techniques for eligibility may be considered, provided they are performed in a CLIA-certified laboratory and are approved by the MSK principal investigator
Pathologically confirmed, mismatch repair-proficient adenocarcinoma of colorectum, who have received at least two prior lines of therapy in the metastatic setting\r\n* Mismatch repair proficiency can be assessed for eligibility by immunohistochemistry (intact expression of MLH, MSH, PMS, and MSH) or by molecular testing in a Clinical Laboratory Improvement Act (CLIA)-certified laboratory for microsatellite instability ( or  microsatellites unstable)
PHASE II: Patients must have histologically or cytologically confirmed, PIKCA mutant metastatic colorectal cancer; PIKCA status must be confirmed by tumor sequencing conducted in a Clinical Laboratory Improvement Act (CLIA) certified lab
PHASE II SCLC: Patients must have histologically or cytologically confirmed diagnosis of SCLC from a Clinical Laboratory Improvement Act (CLIA)-certified laboratory
mCRPC EXPANSION COHORT: Documented histopathological confirmation of prostate cancer from a CLIA- certified laboratory
Patients must have confirmed GBM MGMT status (tumor must be MGMT promoter unmethylated) by central laboratory Clinical Laboratory Improvement Amendments (CLIA) certified testing at MD Anderson, prior to registration. If initial MGMT testing obtained at an outside institution, MGMT status must be centrally retested at MD Anderson.
Androgen receptor will be quantified using a Clinical Laboratory Improvement Act (CLIA)-compliant assay for AR on a biopsy specimen obtained prior to the start of treatment; AR-positivity is defined as >= % of nuclear staining
For cohort , documented activating HER mutation in lung cancer by Clinical Laboratory Improvement Act (CLIA) laboratory, specifically exon  insYVMA (Y Adup), insGSP (G Pdup), insTGT (GdelinsVC), single base pair substitutions L A, LS, VL, VE SF, or another HER mutation approved by the principal investigator
For cohorts , , , documented HER amplification identified through next generation sequencing by Memorial Sloan-Kettering Cancer Center (MSK)-Integrated Mutation Profiling for Actionable Cancer Targets (IMPACT) or at another Clinical Laboratory Improvement Amendments (CLIA) laboratory, or documented HER amplification by in-situ hybridization (ISH) with HER/ centromeric probe for chromosome  (CEP) ratio >= . at a CLIA laboratory; patients with HER amplification identified by another method or criteria must be approved by the principal investigator and may enroll in the other cohort 
Platelets < , cell/mm^ ( x ^/L); qualifying laboratory value must occur at most recent measurement before enrollment and must be no more than  days before enrollment; no transfusions are allowed within  hours before qualifying laboratory value
Hemoglobin <  g/dL; qualifying laboratory value must occur at most recent measurement before enrollment and must be no more than  days before enrollment; no transfusions are allowed within  hours before qualifying laboratory value
Documented histopathological confirmation of prostate cancer from a Clinical Laboratory Improvement Act (CLIA)-certified laboratory
CAPMATINIB INCLUSION CRITERIA: Presence of an oncogenic kinase fusion involving MET, confirmed by assay by a Clinical Laboratory Improvement Act (CLIA)-approved laboratory
CERITINIB INCLUSION CRITERIA: Presence of an oncogenic kinase fusion involving ALK, confirmed by assay by a CLIA-approved laboratory
REGORAFENIB INCLUSION CRITERIA: Presence of an oncogenic kinase fusion involving BRAF or RET, confirmed by assay by a CLIA-approved laboratory
ENTRECTINIB INCLUSION CRITERIA: Presence of an oncogenic kinase fusion involving ROS or NTRK//, confirmed by assay by a CLIA-approved laboratory
Tumor must have labeling index of greater than or equal to % of the nuclear Gli- (integral biomarker performed in the MD Anderson Cancer Center Clinical Laboratory Improvement Amendment [CLIA] laboratory) for patient to be eligible in this trial (if enough archival tissue is not available to determine labeling index, patient must agree to a biopsy to be eligible for the study)
CA less than or equal to  x upper limit of normal (ULN) confirmed within  weeks of randomization using a centralized laboratory assay
Laboratory results within the  weeks prior to Randomization must be as follows:
Patients must have CDKNA-deficient tumor (deletion or mutation); definition of CDKNA deficient tumor:\r\n* CDKNA deletion or mutation by any Clinical Laboratory Improvement Amendments (CLIA)-certified sequencing OR\r\n* >= % of tumor cells with (at least) hemizygous deletion by fluorescent in situ hybridization (FISH); status will be determined from archived tissue
Patients with CDKNA wild type by a CLIA-certified laboratory
Total bilirubin =< . x ULN for the laboratory at the time of enrollment, all forms of biliary stents allowed
Histologically confirmed diagnosis of advanced (metastatic or unresectable) NSCLC with mutations, rearrangement and fusion involving RET oncogene, or abnormalities (non-synonymous single nucleotide variant [SNV] or amplification) in the nintedanib target genes VEGFR-, TP, PDGFR-A, PDGFR-B, or FGFR-; Clinical Laboratory Improvement Act (CLIA) certified lab testing for nintedanib target genes using cell free DNA from peripheral blood and/or assays performed on tumor tissues are acceptable
Patients must have activating genomic alterations in FGFR (mutations, fusions or amplifications [>  copies]) or activating genomic alterations in mast/stem cell growth factor receptor kit (KIT), platelet-derived growth factor receptor alpha (PDGFR alpha), ret proto-oncogene (RET), ABL proto-oncogene , non-receptor tyrosine kinase (ABL) and fms-related tyrosine kinase  (FLT) by any validated Clinical Laboratory Improvement Amendments (CLIA)-certified molecular testing (fluorescent in situ hybridization [FISH], polymerase chain reaction [PCR] or sequencing data are acceptable); CLIA validated results from other institutions; diagnostic labs (e.g. foundation medicine) are acceptable
BRAF mutation-positive melanoma (VE or VK) based on report from a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory
Histologically confirmed diagnosis of advanced (metastatic or unresectable) non-small cell lung cancer (NSCLC) with mutations, rearrangement and fusion involving RET oncogene, or abnormalities in the pazopanib target genes defined as vascular endothelial growth factor receptors - (VEGFR-), platelet-derived growth factor receptor-alpha (PDGFRA), or platelet-derived growth factor receptor-beta (PDGFRB), or tumor protein p (TP) with abnormalities including deletion, insertion, early stop codon, and/or nonsynonymous mutations with functional consequences; Clinical Laboratory Improvement Act (CLIA) certified lab testing for pazopanib target genes using cell free deoxyribonucleic acid (DNA) from peripheral blood and/or assays performed on tumor tissues are acceptable
COHORT A: Confirmation in a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory that one of the patients thyroid tumors (primary tumor, recurrent tumor, or metastasis) has an neuroblastoma RAS viral (v-ras) oncogene homolog (NRAS) or Kirsten rat sarcoma viral oncogene homolog (KRAS) or Harvey rat sarcoma viral oncogene homolog (HRAS) mutation at G, G, or Q; this group of patients will also be referred to as RAS MUT
RECIPIENT: Mutation in the GATA gene, or evidence of loss of expression of one allele of GATA, by complementary deoxyribonucleic acid (cDNA) analysis performed by a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory, or the clinical syndrome of MonoMAC
MATCHED RELATED DONOR: Mutation in GATA, or evidence of loss of expression of one allele of GATA by cDNA analysis performed by a CLIA certified laboratory, or in the case where the mutation in GATA has not been identified, but the recipient has the clinical syndrome of MonoMAC, the donor is excluded if he or she has the clinical syndrome of MonoMAC
HAPLOIDENTICAL RELATED DONOR: Mutation in GATA, or evidence of loss of expression of one allele of GATA by cDNA analysis performed by a CLIA certified laboratory, or in the case where the mutation in GATA has not been identified, but the recipient has the clinical syndrome of MonoMAC, the donor is required to have no clinical history of MonoMAC
Patients must have a tissue or blood proven KRAS or EGFR mutation confirmed in a Clinical Laboratory Improvement Amendments (CLIA) certified lab (only required in the Phase IB expansion cohort)
Required baseline laboratory data
Diagnosis of dyskeratosis congenita based on clinical triad of abnormalities of skin pigmentation, nail dystrophy, oral leukoplakia; OR one of clinical triad and presence of two or more associated features; OR a pathogenic mutation in DKC,TERC, TERT, NOP, NHP, TCAB, TINF, CTC, PARN, RTEL, or ACD as reported by a CLIA-approved laboratory; OR age-adjusted mean telomere length < %ile in peripheral blood lymphocytes as reported by a CLIA-approved laboratory; OR Hoyeraal-Hreidarsson syndrome; OR Revesz syndrome
FA demonstrated by a positive test for increased sensitivity to chromosomal breakage with mitomycin C or diepoxybutane performed by a Clinical Laboratory Improvement Amendments (CLIA) or College of American Pathologists (CAP) approved laboratory
DOCK deficiency with the two criteria listed below:\r\n* Clinical history of one or more episodes of life-threatening or severely disfiguring infection with opportunistic organisms, including severe recurrent cutaneous and sinopulmonary infections with bacterial or fungal infection, or viral infections with herpes simplex, herpes zoster, Molluscum contagiosum, or human papilloma virus\r\n* Homozygous or compound heterozygous mutations in the DOCK gene performed by a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory
Required baseline central laboratory data in protocol.
Cancer must have at least one of the following PIKCA mutations: EK, EK, HR, HL; the PIKCA mutation must be documented in a Clinical Laboratory Improvement Amendments (CLIA) approved laboratory
Laboratory data:
Patients must have one of the histologically advanced solid tumors harboring CCNE amplification: their diseases are refractory to, or do not have, standard-of-care therapy; or they declined standard-of-care therapy; patients with triple negative breast cancer or small cell lung cancer are not eligible since there is an ongoing phase Ib study of AZD as a single agent targeting these patients; CCNE amplification is defined in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory: CCNE amplification >  based on targeted custom Ampliseq panel on the Ion Torrent PGM; or CCNE amplification on alternate CLIA platforms such as Foundation One, UW-OncoPlex  Cancer Gene Panel, Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT), Solid Tumor Genomic Assay (Life Technologies), etc. will also be eligible to be treated after principle investigator (PI) approval; patients with known CCNE amplification on local or commercial platforms can start treatment after planned biopsy or submission of recent archival sample; central next-generation sequencing (NGS) CCNE and fluorescence in situ hybridization (FISH) testing will be performed to confirm the result
RENAL & BLADDER COHORT: Consent to Monroe Dunaway (MD) Anderson laboratory protocol PA-
Stage IV or metastatic/recurrent non-small cell lung cancer; for expansion cohorts, patients tumor must also harbor a KRAS mutation detected in a CLIA certified laboratory
For phase I dose expansion cohorts the patients tumor must harbor a KRAS mutation detected by a CLIA certified laboratory
Patient has an AR-positive and PTEN-positive tumor as determined by using Clinical Laboratory Improvement Amendments (CLIA) compliant assays to identify AR-positive and PTEN-positive disease (AR positivity is defined as >= % of nuclear staining, PTEN positivity is defined as > % of nuclear staining).
Documented deleterious BRCA/ or PALB mutation (germline or somatic) as assessed by Clinical Laboratory Improvement Amendments (CLIA) certified laboratory; variants that are considered to be non-detrimental (variants of uncertain significance, variants of unknown significance, variant, favor polymorphism or benign polymorphism etc) are not sufficient for study entry
Required initial laboratory data (normal limits per treating institution; minor changes from the indicated laboratory guidelines will be allowed at the discretion of the treating team under special circumstances and reasons for the changes will be documented):
Carcinoma must be HPV-associated, which is defined as positive for p protein by immunohistochemistry (IHC); p positivity is defined as >= % of tumor cells demonstrating diffuse cytoplasmic and nuclear staining for p by immunohistochemistry in a Clinical Laboratory Improvement Amendments (CLIA) certified pathology lab. p testing is standard at participating institutions and may be conducted locally
Tumors must have undergone expanded molecular profiling with a Clinical Laboratory Improvement Act (CLIA)-certified platform that evaluates, at a minimum, RAS, PIKCA, PTEN and BRAF mutations status
Patient has a PIKCA mutation confirmed by Novartis designated central lab or patient has a pathology report confirming PIKCA mutant status by certified laboratory (using validated PIKCA mutation assay) either from tissue or blood and must (mandatory) send tumor tissue to Novartis designated central lab for confirmation of mutational status
To be eligible for the study all participants (Cohort  and ) are required to provide genomic profiling data from assays performed in a Clinical Laboratory Improvement Act (CLIA)-certified lab that demonstrate the following with respect to relevant biomarkers required for enrollment to the study as listed below; results from genomic profiling must be sent to the DFCI Coordinating Center prior to enrollment of the participant for central pathology review\r\n* Inactivation of CDKNA/B or C in the tumor by homozygous deletion (evidence or more than single copy loss for any of the genes defined as array comparative genomic hybridization [CGH] log ratio of < . by array CGH; or from sequencing data with sufficient coverage for evaluation) AND\r\n* Validation of wild-type RB status (no deletion/losses more than single copy by copy number or sequencing data; and/or no inactivating mutations by sequencing)
The subject must have all of the following results as part of screening laboratory assessments (results from either the central laboratory or a local laboratory can be used for qualification):
Patients with previously identified IDH/ mutations from a Clinical Laboratory Improvement Act (CLIA) certified laboratory can be enrolled on the trial, but must be verified in the central study laboratory
MGMT promoter methylation testing will be performed by an institutional Clinical Laboratory Improvement Amendments (CLIA)-approved laboratory using a methylation specific polymerase chain reaction (PCR) assay to detect deoxyribonucleic acid (DNA) methylation within the promoter region of the MGMT gene\r\n* Participants with an MGMT promoter that is unmethylated will be enrolled to cohort a, while those with tumor MGMT promoter that is methylated, partially methylated, indeterminate or unknown will be enrolled to cohort b
Documented laboratory (lab) results confirming tumor mutational status must be obtained at screening; patients in whom mutational status cannot be determined will be deemed ineligible
Patients must have BRAFVE or BRAFVK mutations, identified by a Food and Drug Administration (FDA)-approved test at a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory (lab); if test at CLIA-certified lab used a non-FDA approved method, information about the assay must be provided
Formalin-fixed, paraffin-embedded tumor tissue must be submitted to Baylor College of Medicine (BCM)  Cancer Genetics Laboratory for Clinical Laboratory Improvement Amendments (CLIA)-certified KRAS mutation testing; results must be reported on the eligibility checklist during registration in order to receive treatment assignment\r\n* Note: if CLIA-certified KRAS mutation tumor testing is available from local or other source (e.g., Foundation Medicine) this report can be submitted to Statistical and Data Center (SDC) to meet this requirement
Melanoma must be documented to contain a BRAFV mutation by a Clinical Laboratory Improvement Amendment (CLIA) approved laboratory
Please contact study investigator and/or consult protocol document for specific details on laboratory criteria
Physical and Laboratory Test Findings
Patients K-ras status must be wild type (not mutated); K-ras status determination may be based on either primary or metastatic tumor\r\n* NOTE: the assay must be performed by a Clinical Laboratory Improvement Amendments (CLIA) approved laboratory
DISEASE RELATED CRITERIA: Patients must have pathologically confirmed KRAS mutation (at codon ,  and ) positive non-small cell lung cancer (NSCLC) that is stage IV or recurrent; the specific subtype of KRAS mutation must be known; KRAS mutation testing must have been performed in a Clinical Laboratory Improvement Act (CLIA) certified laboratory; CLIA certified commercially available tests are acceptable
Presence of p del by central laboratory.
Presence of q del by central laboratory.
Escalation Phase [Inclusion]\n\n          -  Locally advanced or metastatic adult solid tumor that has progressed or was\n             nonresponsive to available therapies, are unfit for standard chemotherapy or for which\n             no standard or available curative therapy exists;\n\n          -  ECOG score of ,  or ;\n\n          -  Adequate hematologic, hepatic, and renal function;\n\n        Expansion Phase [Inclusion]\n\n          -  Escalation Phase inclusion criteria\n\n          -  Evidence of the NTRK fusion as previously determined with prior testing from a\n             Clinical Laboratory Improvement Amendments (CLIA)-certified or equivalent certified\n             laboratory.\n\n        Exclusion (for both Escalation and Expansion)\n\n         Current treatment with a strong cytochrome P (CYP) A inhibitor or inducer (EIAEDs\n        and dexamethasone for CNS tumors or metastases, on a stable dose, are allowed)
Identification of a drug target/targets through molecular profiling performed as a part of routine clinical care and treatment recommendation by the Mayo Clinic Genomics Tumor Board (GTB); NOTE: If profile matches more than  treatment arm, final decision for treatment arm assignment to be made by patients treating physician; it will be required for the genomic aberration to be identified through a test in a Clinical Laboratory Improvement Amendments (CLIA) workflow; assays used will range from single gene abnormalities (e.g. fluorescent in situ hybridization [FISH] for human epidermal growth factor receptor  [ERBB] amplifications) to next generation sequencing based gene panels (Foundation One) to more comprehensive assays such as whole exome sequencing; the Mayo Clinic GTB will serve as the centralized point of data synthesis to allow for assessment of molecular profiling accomplished through a heterogeneous array of tests
SUB-PROTOCOL AIM A: Confirmation of advanced cancer with mTOR pathway aberrations as determined through routine clinical care using pathway aberrations performed in a CLIA certified laboratory; cancer genomic profiling tests incorporating next generation sequencing from archival formalin-fixed paraffin-embedded tissue (FFPE) are validated with sensitivities and specificities of % and %, respectively; in the assay, hybrid-captureselected deoxyribonucleic acid (DNA) libraries are sequenced to depths targeting >   coverage by non-polymerase chain reaction (PCR) duplicate read pairs, with > % of exons at coverage >  ); multiplatform profiling may include immunohistochemistry and in situ hybridization methods with previously established negative/positive cutoffs performed in a CLIA certified lab; at least one pathway aberration must be identified; these must be confirmed in a CLIA certified lab; the potential mTOR aberrations that could be identified are listed below, please note that this list is not all inclusive; if a CLIA validated report lists an mTOR pathway inhibitor as a target drug for a genetic aberration, then it can be considered eligible for the purposes of this study; v-akt murine thymoma viral oncogene homolog  (AKT), MTOR, phosphatidylinositol-,-bisphosphate -kinase, catalytic subunit alpha (PIKCA), tuberous sclerosis (TSC), TSC, retrovirus-associated DNA sequence (Ras) homolog enriched in brain (RHEB), serine/threonine kinase  (STK), neurofibromin (NF)/
Required baseline laboratory data as outlined in protocol
Determined to have detectable mutations in codons  or  of the kirsten rat sarcoma (KRAS) oncogene by an investigational assay at the study JPBK central laboratory. A KRAS positive mutation result in codons  or  of the KRAS oncogene from tumor tissue per local laboratory will be permitted in no more than % of randomized participants.
Completion of all necessary baseline laboratory and radiologic investigations prior to randomization
Abnormal laboratory tests immediately prior to randomization
Results must be available from a genomic test or immunohistochemistry (IHC) test for protein expression performed in a Clinical Laboratory Improvement Amendments (CLIA)-certified, College of American Pathologists (CAP) -accredited, New York State accredited (for labs offering services to residents of NY) laboratory that has registered the test with the National Institutes of Health (NIH) Genetic Test Registry or has established an integration with the TAPUR platform. The genomic or IHC test used to qualify a patient for participation in TAPUR may have been performed on any specimen of the patient's tumor obtained at any point during the patient's care at the discretion of the patient's treating physician. Genomic assays performed on cell-free DNA in plasma (\liquid biopsies\) will also be acceptable if the genomic analysis is performed in a laboratory that meets the criteria described above.
If HER negative by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH), but activating somatic mutations of HER gene identified through genomic sequencing including but not limited to the following (Clinical Laboratory Improvement Act [CLIA] certified lab test): missense substitutions (GA, GE, SF, SY, SC, VE, RQ, VL, TI, LS, LP, EA, DH, DY, DN, GV, GC, VL, LV, VI, RW, LR, RC); insertions/deletions (A_GinsYVMA aka Y_Adup, GVinsC, GAinsVGC, G insertions, G_SinsCPG, P_insGSP aka G_Pdup, L_Tdel) and/or HER activating mutations; there is no limitation on the number of prior lines of systemic therapy or HER-targeted therapies (prior neratinib not allowed)
Recurrent respiratory papillomatosis (RRP) criteria\r\n* Histological diagnosis of RRP confirmed by pathology report from a Clinical Laboratory Improvement Act (CLIA)-certified laboratory\r\n* One of the following:\r\n** A Derkay anatomic score of  or greater and a history of two or more endoscopic interventions in the last  months for control of RRP\r\n** Pulmonary RRP with pulmonary disease that is measurable by computed tomography scan\r\n** Tracheal involvement with RRP that has required either two or more endoscopic interventions in the last  months or a tracheostomy
Patients must have either isocitrate dehydrogenase  (NADP+), soluble (IDH) or isocitrate dehydrogenase  (NADP+), mitochondrial (IDH) mutations (any known mutations) based on the SNaPshot platform or other molecular testing platform from either archived tissue or fresh biopsy (tested in Clinical Laboratory Improvement Amendments [CLIA]-certified lab)
Confirmation of advanced biliary cancer that is refractory or intolerant to gemcitabine or fluoropyrimidine based therapy with FGFR fusion [using next-gen sequencing assays (such as Foundation One) or fluorescent in situ hybridization (FISH) break-apart assays] or FGFR pathway mutation/amplification [using next-gen sequencing assays (such as Foundation One)]; assays must be performed in a Clinical Laboratory Improvement Amendments [CLIA] certified laboratory and done as a CLIA validated test or research use only [RUO] in a CLIA laboratory
Confirmation in a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory or in an Food and Drug Administration (FDA)-approved assay that one of the patients thyroid tumors (primary tumor, recurrent tumor, or metastasis) possesses a BRAF mutation at V
Patients must have histologically or cytologically confirmed adenocarcinoma of esophagus or gastroesophageal junction, or stomach which is Gli- positive (labeling index [LI] greater than or equal to %); testing is to be performed in a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory; the patients must have an archival tumor sample to facilitate this testing
Agreed to participate in laboratory protocol PA- for the testing of biomarkers as described in this clinical protocol
All subjects must have EITHER the clinical diagnosis of NF using the National Institute of Health (NIH) consensus conference criteria, OR have a constitutional NF mutation documented in a Clinical Laboratory Improvement Amendments (CLIA)/College of American Pathologists (CAP) certified lab
Absence of Kit and PDGFRA mutation confirmed in a Clinical Laboratory Improvement Act (CLIA) certified laboratory
COHORT I: Patients must have MM that harbors an NF mutation believed to cause functional loss of the NF protein as determined by any Clinical Laboratory Improvement Act (CLIA) lab certified next generation sequencing (NGS) platform or NF loss must be documented by CLIA certified immunohistochemistry (IHC)
KRAS mutation positive tumour sample as determined by the designated testing laboratory
Patients must have BRAF^V mutant metastatic cancer irrespective of the histology or prior therapy; BRAF^V mutant status must be documented by a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory; use of an Food and Drug Administration (FDA)-approved test is preferred although other BRAF tests at a CLIA-certified laboratory may also be accepted
Carcinoma of the oropharynx associated with HPV as determined by p protein expression using immunohistochemistry (IHC) performed by a Clinical Laboratory Improvement Amendments (CLIA) approved laboratory; using p antibody obtained from Roche mtm laboratories AG (CINtec, clone EH) is recommended
Patients must be HLA-A as determined by a CLIA certified (or equivalent) clinical laboratory. (This determination will be made under a pre-enrollment screening ICF)
Laboratory requirements:
Cancers with positive BRAF V mutation detected by a Clinical Laboratory Improvement Act (CLIA)-certified laboratory
Patients with known K-RAS mutant (codon  or ) detected by a Food and Drug Administration (FDA)-approved test in a CLIA-certified laboratory
Presence of NRAS Q mutation in tumor tissue prior to randomization as determined by a Novartis designated central laboratory
Prospective confirmation of KRAS mutation negative status as determined via an AZ approved laboratory
Patient has achieved MR. (local laboratory assessment) during nilotinib treatment, and determined by a Novartis designated central PCR lab assessment at screening
Baseline paraffin embedded tissue from the patients primary diagnosis is requested before study enrollment and should be forwarded to the designated central laboratory where central assessment of Rb and p expression will be performed by using immunohistochemistry; in patients with measurable disease a tissue biopsy may be obtained by core biopsy and submitted to the designated central laboratory
Laboratory test results within these ranges:
Test positive by FISH by the central laboratory designated by the Sponsor
Have FGFR gene fusion documented by a local or central laboratory using standard protocols and approved by local IRB/EC, by CLIA or other similar agency. If the FGFR gene fusion is identified by a laboratory other than the Sponsor's central laboratory, then archival and/or recent tissue biopsy samples or a tissue block suitable for genetic testing must be available for confirmatory testing by FISH by the Sponsor's central laboratory. If a subject has documentation from the central laboratory indicating that they test negative for FGFR gene fusion, that subject may not be enrolled in the study.
NTRK gene fusions will be identified via a CLIA certified (or equivalent) laboratory. Exception: Patients with Infantile Fibrosarcoma (IFS) and congenital mesoblastic nephroma (CMN) may be enrolled based on ETV+ FISH test without identifying NTRK
p/q deletion status assessment as determined by the Mayo Cytogenetics Laboratory has been received
All patients must have definitive evidence of t(;) or inv() by a Clinical Laboratory Improvement Amendments (CLIA) approved cytogenetics laboratory from initial diagnosis
Positive for RAS mutation (neuroblastoma RAS viral [v-ras] oncogene homolog [NRAS] codon , ,  mutation or Kirsten rat sarcoma viral oncogene homolog [KRAS] codon , ,  mutation) at a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory prior to study entry; mutational testing will be performed on bone marrow sample and/or peripheral blood; patients with previously known RAS mutations prior to study entry may be considered positive for RAS mutation for eligibility prior to a CLIA-certified laboratory confirmation of such a mutation at the discretion of the investigator; (appropriate blood and/or bone marrow samples must be taken for RAS determination and submitted to a CLIA-certified laboratory prior to study entry); however, if such a mutation is not confirmed by the M D Anderson Cancer Center (MDACC)/other centers CLIA-certified laboratory, the patient may be permitted to stay on the study if they wish and consent to do so but such patients data will be analyzed separately
Acceptable laboratory results as indicated by protocol
Diagnosis of relapsed or refractory AML of any French American British (FAB) subtype except M and NPM genetic mutation detected by molecular assay; AML patients treated at Stanford have NPM molecular mutation status checked routinely at time of diagnosis in a Clinical Laboratory Improvement Amendment (CLIA)-certified laboratory
Positive for PIKCA mutation based on central laboratory testing
ERLOTINIB HYDROCHLORIDE ARM: Patients must have an EGFR tyrosine kinase inhibitor (TKI) sensitizing mutation as determined by analysis of the primary tumor or a metastatic site in a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory
Patients tumors must have known PIK pathway activation defined as EITHER of the following on a Clinical Laboratory Improvement Amendments (CLIA)-approved molecular diagnostics test:\r\n* Genomic alteration resulting in loss of phosphatase and tensin homolog (PTEN) function including a whole or partial gene deletion, frame shift mutations, or non-sense mutations; missense mutations in PTEN will not be considered qualifying\r\n* A previously characterized activating mutation in any component of the pathway including: phosphatidylinositol-,-bisphosphate -kinase, catalytic subunit alpha (PIKCA), v-akt murine thymoma viral oncogene homolog  (AKT), phosphoinositide--kinase, regulatory subunit  (alpha) (PIKR), phosphoinositide--kinase, regulatory subunit  (beta) (PIKR), mTOR
Local testing for EGFR-mutations for this study is acceptable provided it was performed in a Clinical Laboratory Improvement Act (CLIA) certified lab
Patient must have acceptable, applicable laboratory requirements
CCND amplification and/or loss of p as determined by the central laboratory.
Tumors with at least one of the following known mutations in the PI-K signaling pathway, via assays performed in a Clinical Laboratory Improvement Act (CLIA)-approved setting (Foundation Medicine FoundationOne test will be used; this assay uses a cut-off of % allele fraction for mutations; allele fraction will be requested on each sample):\r\n* PIKCA,\r\n* PIKCG, \r\n* PIKR, PIKR and PIKAP (regulatory subunits), \r\n* AKT and mTOR, or\r\n* PTEN \r\n** Note: PIKCA amplification is not eligible
Other baseline laboratory evaluations must be done within  days prior to randomization.
BRAF V mutation-positive tumor: as confirmed by a Clinical Laboratory Improvement Amendments (CLIA) approved local laboratory or equivalent.
Molecular characterization of the tumor demonstrating a KRAS mutation by a CLIA-certified assay. Adequate archival tissue, tissue core biopsy specimen, or DNA samples must be available for central testing of INKa/Arf and p if not previously performed by a CLIA certified lab.
Evidence of lack of HER oncogene amplification as determined by FISH testing by central laboratory
Uric acid, if elevated, must be corrected to within laboratory normal range prior to dosing
Additional Laboratory Requirements
Physical and Laboratory Test Findings
Specific to the cohorts as designed to enroll patients with tumor protein p (TP) mutations: TP mutations are identified by next-generation sequencing in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory prior to screening
EXPANSION COHORT B ONLY: documented genetic alteration (mutation or homozygous deletion) in the PTEN gene, identified by the MSKCC Integrated Mutation Profiling of Actionable Cancer Targets (IMPACT) assay platform or other Clinical Laboratory Improvement Amendments (CLIA)-approved test
Liver toxicity criteria based on local laboratory results obtained within  hours of Baseline:
Consent to MD Anderson laboratory protocol PA-
RAS wild-type status (by a Clinical Laboratory Improvement Amendments [CLIA] certified assay that includes all known mutations in Kirsten rat sarcoma viral oncogene homolog [KRAS], Harvey rat sarcoma viral oncogene homolog [HRAS], and neuroblastoma RAS viral [v-ras] oncogene homolog [NRAS])
Laboratory evaluation:
Documentation from the enrolling site confirming the presence of IDH mutation and p/q status; the provided information must document assays performed in clinical laboratory improvement amendments (CLIA)-approved laboratories and be uploaded prior to Step  registration
GLIOMA PATIENTS: Standard of care next generation sequencing via a Clinical Laboratory Improvement Act (CLIA) certified platform must be available and at a minimum include IDH, RB, and ATRX status
For Part B, participants must have one of the following diagnoses histologically confirmed:\r\n* Neuroblastoma with evidence of mycn/myc positivity based on any of the following:\r\n** MYCN amplification (>  copy amplification) from Children's Oncology Group (COG) reference laboratory or other Clinical Laboratory Improvement Act (CLIA)-certified laboratory; or\r\n** Mycn protein expression >= + according to validated assay in Childrens Hospital Los Angeles (CHLA) Clinical Pathology Laboratory; or\r\n** Myc expression >= + according to validated assay in CHLA Clinical Pathology Laboratory\r\n* One of the following mature B cell lymphoma diagnoses:\r\n** Diffuse large B cell lymphoma\r\n** Burkitt lymphoma\r\n* An extra-cranial, solid tumor, other than neuroblastoma, with evidence of MYC or MYCN-alteration based on either of the following:\r\n** MYC or MYCN amplification from a CLIA-certified laboratory\r\n** MYC or MYCN high copy gain from a CLIA-certified laboratory
Diagnosis of familial adenomatous polyposis (FAP) or attenuated familial adenomatous polyposis (AFAP), defined as at least one of the following:\r\n* Genetic diagnosis with confirmed APC mutation (Clinical Laboratory Improvement Act [CLIA] certified lab or research testing)\r\n* Obligate carrier\r\n* Clinical diagnosis of classic FAP with >=  colorectal adenomas status post colectomy and a family history of FAP\r\n* Clinical diagnosis of FAP, based on personal and family history; Note: This criterion requires documented review and agreement from either the study chair or the Cancer Prevention Network (CPN) lead investigator
Activating Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation (any G, G, Q) confirmed by Clinical Laboratory Improvement Act (CLIA)-certified testing
Patients who are diagnosed with NF using the National Institutes of Health (NIH) Consensus Conference criteria or have a confirmed NF mutation with analysis performed in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory; NF mutation testing to confirm eligibility will not be performed on this protocol, but as part the POB separate screening study
Abnormalities in hematological, clinical chemical or any other laboratory variables at Screening measured by the central or local laboratory regarded as clinically relevant by the investigator unless they are due to underlying disease or condition.
Cohort B and Expansion: Screening visit peripheral blood must be submitted for central analysis at a sponsor-designated laboratory to identify spliceosome hotspot mutations in SFB, SRSF, UAF, mutations in ZRSR, and SRSF deletion including amino acid P.
Peripheral blood MDSC level ? % of mononuclear cell fraction (assayed at a central laboratory)