Histological or cytological evidence of urothelial cancer of the bladder, urethra, ureter, or renal pelvis; differentiation with variant histologies (e.g., squamous cell differentiated) will be permitted provided that the predominant histology is urothelial carcinoma
Cohort A2: Transitional cell carcinoma of the urothelium including the bladder, urethra, renal pelvis, and ureter.
Have locally advanced (on TNM staging: T4b and any N, or any T and N2-3) or metastatic transitional cell carcinoma of the urothelium, including of the urinary bladder, urethra, ureter, and/or renal pelvis. The diagnosis must be histologically or cytologically confirmed.
Have histologically or cytologically confirmed locally advanced or metastatic transitional cell carcinoma of the urothelium (renal pelvis, ureter, urinary bladder or urethra)
Histologically confirmed muscle-invasive UC (also termed transitional cell carcinoma) of the bladder or upper urinary tract (i.e., renal pelvis or ureters)
Subject has histologically confirmed diagnosis of any one of the following cancers: (A) urothelial cancer (transitional cell cancer of the bladder, ureter or renal pelvis), (B) melanoma, or (C) squamous cell carcinoma of the head and neck.
Subjects with primary TCC of the ureter, urethra, or renal pelvis without TCC of the bladder are not allowed
(Part 2 only) Cohort 3: Have histologically or cytologically confirmed diagnosis of metastatic or locally advanced TCC of the urinary tract (bladder, urethra, ureter, renal pelvis) (T3b-T4 N0 M0, Tany N1-N3 M0, or Tany Nany M1) and are not candidates for surgery.
Patients with concurrent upper urinary tract (i.e. ureter, renal pelvis) non-invasive urothelial carcinoma
Cohort D: unresectable or metastatic urothelial carcinoma (urethra, bladder, ureters, or renal pelvis)
Have histologically or cytologically documented locally advanced unresectable or metastatic/recurrent urothelial carcinoma (including renal pelvis, ureters, urinary bladder, and urethra);
Histologically documented, locally advanced (T4b, any N; or any T, N 2?3) or metastatic urothelial carcinoma (mUC) (M1, stage IV) (also termed TCC or UCC of the urinary tract; including renal pelvis, ureters, urinary bladder, and urethra). Patients with mixed histologies are required to have a dominant transitional cell pattern. Locally advanced bladder cancer must be inoperable on the basis of involvement of pelvic sidewall or adjacent viscera (clinical stage T4b) or bulky nodal metastasis (N2?N3)
Dose Escalation, Renal insufficiency and CPI-Treated Expansion cohorts: Histologically confirmed Transitional Cell Carcinoma of the Urothelium (TCCU) (i.e., cancer of the bladder, renal pelvis, ureter, or urethra). Subjects with Urothelial Carcinoma with squamous differentiation or mixed cell types are eligible.
PRE-CHEMORADIATION SAMPLE COLLECTION: Patients must have histologically proven primary carcinoma of the bladder or urethra or lower ureter (adenocarcinoma or transitional or squamous-cell carcinoma)
STUDY TREATMENT: Patients must have histologically proven primary carcinoma of the bladder or urethra or lower ureter (adenocarcinoma or transitional or squamous-cell carcinoma)
Histological or cytological evidence urothelial (transitional cell) carcinoma of the renal pelvis, ureter, bladder or urethra
Subject has histologically confirmed diagnosis of any one of the following cancers: urothelial cancer (transitional cell cancer of the bladder, ureter, urethra or renal pelvis), melanoma, squamous cell carcinoma of the head and neck, ovarian cancer, NSCLC (squamous, adenosquamous, or large cell), esophageal (squamous and adenocarcinoma) or gastric cancer, synovial sarcoma or MRCLS.
Histological or cytological evidence of transitional cell carcinoma or carcinoma in situ of the urothelium involving the bladder or prostatic urethra following treatment with BCG with the recommendation to proceed for cystectomy; minor histologic variants (< 50% overall) are acceptable; diagnosis must be within 1 year of study entry
Patients must have a histologically confirmed diagnosis of metastatic, progressive urothelial carcinoma of the bladder, urethra, ureter, or renal pelvis
UROTHELIAL CARCINOMA EXPANSION COHORT: Patients must have a histologically confirmed diagnosis of urothelial carcinoma of the bladder, urethra, ureter, or renal pelvis from a CLIA-certified laboratory, with measurable disease by RECIST (version 1.1) including lymphadenopathy and visceral metastatic disease
Concurrent extra-vesical (i.e., urethra, ureter, or renal pelvis) non-muscle invasive transitional cell carcinoma of the urothelium
Histologically documented metastatic or surgically unresectable urothelial carcinoma; may include primary site from ureters, upper tract, renal pelvis, and bladder.
Documented urothelial carcinoma (transitional cell carcinoma) including urinary bladder, renal pelvis, ureters, urethra meeting all of the following criteria
Histological or cytological proof of urothelial carcinoma of the urethra, bladder, ureters, or renal pelvis
Histologically confirmed diagnosis of urothelial carcinoma of the bladder, urethra, ureter, or renal pelvis
Patients must have histologically or cytologically documented locally advanced/inoperable or metastatic urothelial bladder carcinoma (UBC), including renal pelvis, ureters, urinary bladder, and urethra\r\n* Note: mixed histology tumors allowed if predominant histology is urothelial carcinoma\r\n* Note: small cell or neuroendocrine carcinoma is not allowed if predominant
For the dose expansion part: Patients with histologically confirmed, locally advanced or metastatic urothelial carcinoma (transitional cell carcinoma) including urinary bladder, renal pelvis, ureters, urethra who are not candidates for or refuse standard therapy or whose disease progressed and for which standard anticancer treatment is no longer effective.
Histologically confirmed urothelial carcinoma of the bladder, ureter, urethra, or renal pelvis by the enrolling institution; patients with mixed histologies are required to have a predominant urothelial component as reviewed by the pathologist at the enrolling institution
Must have had invasive urothelial cancer at high risk of recurrence originating in the bladder, ureter, or renal pelvis
Participants must have stage IV, locally advanced or metastatic (T4b, any N; or any T, N2-3) urothelial bladder cancer or TCC arising in another location of the urinary tract, including urethra, ureter, and renal pelvis; the diagnosis must be histologically or cytologically confirmed; mixed histologies are permitted as long as TCC is the major component (i.e. > 50% of the pathologic specimen); pure or predominant squamous cell carcinomas or adenocarcinomas are not permitted
Cytologically or histologically confirmed evidence of transitional cell carcinoma of bladder, renal pelvis, ureter or urethra
Has a histologically or cytologically confirmed diagnosis of advanced/unresectable (inoperable) or metastatic urothelial carcinoma of the renal pelvis, ureter [upper urinary tract], bladder, or urethra. Both transitional cell and mixed transitional/non- transitional cell histologies are allowed, but transitional cell carcinoma must be the predominant histology.
Have histologically or cytologically confirmed, locally advanced or unresectable or metastatic urothelial (transitional cell) carcinoma of the bladder, urethra, ureter, or renal pelvis.
Have received prior systemic taxane therapy for transitional cell carcinoma (TCC) of the bladder, urethra, ureter, or renal pelvis in any setting (neoadjuvant, adjuvant, metastatic).
Histologically or cytologically confirmed urothelial carcinoma of the renal pelvis, ureter, urinary bladder, or urethra that is transitional cell or mixed transitional/nontransitional (predominantly transitional) cell type.
Histologically confirmed Transitional Cell Carcinoma of the Urothelium (TCCU) (i.e., cancer of the bladder, renal pelvis, ureter, or urethra). Subjects with Urothelial Carcinoma with squamous differentiation or mixed cell types are eligible.
Has histopathologically confirmed transitional cell carcinoma of the urothelium (bladder, urethra, or renal pelvis) with documented disease progression after 1-3 prior lines of systemic therapy
Histologically-confirmed diagnosis of urothelial carcinoma of the renal pelvis, ureter, bladder, or urethra, that is transitional cell, or mixed transitional/non-transitional (predominantly transitional) cell type.
Histologically or cytologically-confirmed diagnosis of advanced/unresectable (inoperable) or metastatic urothelial cancer of the renal pelvis, ureter, bladder, or urethra.
benign low grade transitional cell carcinoma of the bladder
Patients must have a histologically confirmed diagnosis of urothelial carcinoma of the bladder, urethra, ureter, or renal pelvis; confirmation may be obtained from any Clinical Laboratory Improvement Amendments (CLIA) certified laboratory (lab)
Patients must have a histologically confirmed diagnosis of urothelial carcinoma of the bladder, urethra, ureter, or renal pelvis; confirmation may be obtained from any CLIA certified lab
Patient must have a histologically confirmed diagnosis of non-transitional cell carcinoma of the bladder, urethra, ureter, or renal pelvis including but not limited to squamous cell, neuroendocrine, adenocarcinoma including urachal and sarcomatoid; confirmation may be obtained from any CLIA certified lab
Histologically or cytologically confirmed urothelial carcinoma (confirmed at the enrolling institution) of the bladder, ureter, urethra, or renal pelvis; patients with mixed histologies are required to have a predominant urothelial component as reviewed by the pathologist at the treating institution
Evidence of metastatic or surgically unresectable transitional cell carcinoma of the urothelium involving the bladder,urethra,ureter or renal pelvis
Histologically- or cytologically-confirmed diagnosis of advanced/unresectable (inoperable) or metastatic urothelial cancer of the renal pelvis, ureter, bladder, or urethra (transitional cell and mixed transitional/non-transitional cell histologies)
Histologically or cytologically documented locally advanced or metastatic UBC (including renal pelvis, ureters, urinary bladder, and urethra)
Histologically- or cytologically-confirmed diagnosis of urothelial cancer of the renal pelvis, ureter, bladder, or urethra, that is transitional cell or mixed transitional/non-transitional (predominantly transitional) cell type
Patients must have locally advanced or metastatic predominantly urothelial carcinoma of the bladder, ureter, or urethra that is not amenable to curative surgical treatment
Patients must have histologically confirmed predominantly urothelial carcinoma of the bladder, ureter, or urethra
Histologically or cytologically documented locally advanced or metastatic transitional cell carcinoma of the urothelium (including renal pelvis, ureters, urinary bladder, urethra)
Part B1 only: Patients with histological or cytological diagnosis of NSCLC, HNSCC, melanoma, urothelial bladder carcinoma (including renal pelvis, ureters, urinary bladder, and urethra), gastric or squamous cell carcinoma of the uterine cervix who progressed on or are intolerant to standard therapy, for which no standard therapy is available, or who decline standard therapy.
Histologically- or cytologically-confirmed diagnosis of locally advanced/unresectable (inoperable or not amenable to surgical treatment) and/or metastatic transitional cell urothelial cancer of the renal pelvis, ureter, urinary bladder, or urethra
Subjects with UC (including renal pelvis, ureter, bladder, urethra) after prior platinum-based therapy, or
Expansion Cohort 2: Subjects with UC with transitional cell histology (including renal pelvis, ureter, bladder, urethra) who have progressed on or after platinum-containing chemotherapy
Expansion Cohort 3: Subjects with UC with transitional cell histology (including bladder, renal pelvis, ureter, urethra) who are ineligible for cisplatin-based chemotherapy and have not received prior systemic chemotherapy for inoperable, locally advanced, or metastatic disease
Expansion Cohort 4: Subjects with UC with transitional cell histology (including bladder, renal pelvis, ureter, urethra) eligible for cisplatin-based chemotherapy and have not received prior systemic chemotherapy for inoperable, locally advanced, or metastatic disease
Expansion Cohort 5: Subjects with UC with transitional cell histology (including renal pelvis, ureter, urinary bladder, urethra) who have radiographically progressed on or after one prior immune check-point inhibitor (anti-PD1 or anti-PD-L1) as the most recent therapy for the treatment of inoperable, locally advanced, or metastatic disease.
Subjects must have a pathologic diagnosis of advanced/metastatic urothelial cancer (carcinoma of the bladder, ureter, and/or renal pelvis) and must have failed at least 1 line of prior therapy in the metastatic/unresectable setting
Patients must have a histologically confirmed diagnosis of urothelial carcinoma of the bladder, urethra, ureter, or renal pelvis; confirmation may be obtained from any Clinical Laboratory Improvement Amendments (CLIA) certified lab or
Patient must have a histologically confirmed diagnosis of non-transitional cell carcinoma of the bladder, urethra, ureter, or renal pelvis including but not limited to squamous cell, neuroendocrine, adenocarcinoma including urachal and sarcomatoid; confirmation may be obtained from any CLIA certified lab
Patients in the expansion portion must have:\r\n* Histologically confirmed diagnosis of metastatic:\r\n** Urothelial carcinoma of the bladder, urethra, ureter, renal pelvis, OR\r\n** Clear cell renal cell carcinoma OR\r\n** Adenocarcinoma of the bladder OR\r\n** Non-resectable squamous cell carcinoma of the penis OR\r\n** Squamous cell carcinoma of the bladder AND\r\n* Patients with urothelial cancer or renal cell carcinoma must have progressive metastatic disease defined as new or progressive lesions on cross-sectional imaging; patients must have at least:\r\n** One measurable site of disease (according to RECIST criteria) or bone disease by NaF PET/CT
Participants must have histologically documented metastatic or locally inoperable advanced urothelial carcinoma (bladder, urethra, ureter and renal pelvis) (T4b, N2, N3, or M1 disease. NOTE: Aberrant differentiation such as squamous, glandular (adenocarcinoma), and micropapillary are eligible unless the tumor is considered a pure histological variant according to the pathology report. Participants with small cell histology are not eligible.
UC Cohort (CIT-Treated): Participants with histologically confirmed incurable advanced transitional cell carcinoma of the urothelium (including renal pelvis, ureters, urinary bladder, and urethra) previously treated with anti-PD-L1/PD-1 with or without anti-CTLA-4 (investigational or approved)
Patients with pre-operative histologic confirmation of a bladder lesion other than transitional cell carcinoma
Stage IV, locally advanced or metastatic urothelial bladder cancer or transitional cell carcinoma arising in another location of the urinary tract, including urethra, ureter, and renal pelvis
Histologically documented, locally advanced (T4b, any N; or any T, N2-3) or metastatic urothelial carcinoma (mUC) (M1, Stage IV) (also termed transitional cell carcinoma [TCC] or urothelial cell carcinoma [UCC] of the urinary tract; including renal pelvis, ureters, urinary bladder, and urethra)
Patients must have histologically proven, recurrent, non-muscle invasive urothelial carcinoma of the bladder within 60 days prior to registration; the carcinoma must be stage T1 high-grade, stage CIS, or stage Ta high-grade
Histologic confirmation of non-muscle invasive bladder cancer of the transitional cell carcinoma high-grade subtype
Evidence of muscle-invasive or regional and/or distant metastatic bladder cancer, or high grade urothelial carcinoma in the prostate or upper urinary tract
Unable to be treated with a muscle blockade agent (e.g. pancuronium bromide, atricurium, cisatricurium, etc.)
Diagnosis of muscle-invasive bladder cancer
Pathologically demonstrated BCG-unresponsive, high-risk non-muscle-invasive bladder cancer (NMIBC) defined as CIS with or without papillary component, any T1, or Ta high-grade lesions
Participants may not have current or history of clinically significant muscle disorders (eg, myositis), recent unresolved muscle injury, or any condition known to elevate serum CK levels
Histological proof of non-metastatic muscle-invasive urothelial cell carcinoma of the bladder.
History of muscle cramps or restless legs
Patients must have histologically or cytologically confirmed by National Cancer Institute (NCI) Laboratory of Pathology as high grade non-muscle invasive urothelial (transitional cell carcinoma) of the bladder as follows:\r\n* Carcinoma-in-situ (CIS) with or without papillary tumors\r\n* High-grade Ta or T1 disease based on a biopsy/Transurethral Resection of Bladder Tumor (TURBT) performed within 12 weeks of the initial dose of study treatment; if multiple bladder biopsies/TURBTs are required to confirm eligibility, the timing of the last bladder biopsy to the initial dose of study treatment must be within 12 weeks\r\n* Patients with persistent T1 high grade disease on TURBT following a single induction course of BCG (at least 5 of 6 doses) may also be eligible for this trial provided that the patient is surgically unfit for cystectomy as deemed by the investigator or the patient declines cystectomy
Patient must have a clinical diagnosis of low- to intermediate-risk non-muscle invasive bladder cancer according to the 2016 American Urological Association (AUA) Guidelines, except for strongly-suspected PUNLMP.
Bladder cancer that was muscle invasive or positive for lymph node or distant metastasis
Therapeutic or traumatic metal implant in the skin or muscle of either deltoid region
Therapeutic or traumatic metal implant in the skin or muscle of either deltoid region
Patients with high risk muscle invasive urothelial carcinoma (hydronephrosis, palpable mass on examination under anesthesia, muscle invasive urothelial carcinoma with lymphovascular invasion on pathologic specimen, > T3 disease) or those with lymph node positive or metastatic disease are to be excluded
Patients with worsening steroid myopathy (history of gradual progression of bilateral proximal muscle weakness, and atrophy of proximal muscle groups)
Patients with worsening steroid myopathy (history of gradual progression of bilateral proximal muscle weakness, and atrophy of proximal muscle groups)
Cohort A – T2, Transitional cell carcinoma (TCC) muscle invasive bladder cancer, (patients who are cisplatin ineligible, decline neoadjuvant and/or ineligible for neoadjuvant chemotherapy); must have histological proof of T2, muscle-invasive transitional cell carcinoma of the bladder with no evidence of metastatic; patient with any degree of fixation of the pelvic sidewall are not eligible
Pathologically (histologically) proven diagnosis of non-muscle invasive (Ta, Tis or T1) bladder cancer
Have muscle-invasive (>= T2) bladder cancer
Recurrent high-risk non-muscle-invasive bladder cancer after prior intravesical BCG therapy meeting all of the following criteria: \r\n* Histologically documented diagnosis of urothelial carcinoma confirmed by the Department of Pathology at Memorial Sloan Kettering Cancer Center (MSKCC)\r\n* Documentation of activating FGFR3 mutation or gene fusion on an assay performed in a Clinical Laboratory Improvement Act (CLIA)-certified laboratory\r\n* History of high-grade non-muscle-invasive bladder cancer (NMIBC)\r\n* Clinical evidence of high-grade, stage pTa NMIBC\r\n* Prior intravesical therapy with at least one induction course of BCG\r\n* Multiple papillary lesions with at least one amenable to marker tumor study (=< 1 cm, non-invasive; or could be partially resected to leave a non-invasive lesion =< 1 cm) OR solitary papillary lesion amenable to marker tumor study (=< 1 cm, non-invasive)
History of another malignancy within 5 years prior to randomization except for non-melanomatous carcinoma of the skin or adequately treated, non-muscle-invasive, urothelial carcinoma of the bladder (i.e., TIS, Ta and low-grade T1 tumors)
Muscle-invasive, locally advanced nonresectable, or metastatic urothelial carcinoma (i.e., T2, T3, T4, and / or stage IV)
History of another malignancy within 5 years prior to randomisation except for non-melanomatous carcinoma of the skin; or, adequately treated, non-muscle-invasive urothelial carcinoma of the bladder (i.e. Tis, Ta and low grade T1 tumours).
Therapeutic or traumatic metal implant in the skin or muscle of either deltoid region
Patients with worsening steroid myopathy (history of gradual progression of bilateral proximal muscle weakness, and atrophy of proximal muscle groups)
Therapeutic or traumatic metal implant in the skin or muscle of either deltoid region
Histological proof of muscle-invasive urothelial carcinoma of the bladder (stage cT2-cT3b, N0-1, M0). Subjects with mixed histology are required to have documented dominant transitional cell pattern with no more than 10% squamous differentiation and 10% glandular differentiation. Micropapillary/sarcomatoid/adenocarcinoma/plasmacytoid variants are not allowed.
Localized, muscle invasive urothelial carcinoma (T2-4, N0-1, M0) (mixed histology acceptable) ineligible for cystectomy
Non-muscle invasive, localized bladder cancer (Tis, Ta, T1)
Prior systemic chemotherapy for bladder cancer; prior intravesical chemotherapy for the treatment of non-muscle invasive urothelial bladder cancer (UBC) is allowed
Diagnosis of presumed non-muscle invasive bladder cancer based on office based cystoscopy (primary or recurrent), and planned transurethral resection of bladder tumor (TURBT)
Current or history of clinically significant muscle disorders (e.g., myositis), recent unresolved muscle injury, or any condition known to elevate serum CK levels
Histologically-confirmed non muscle-invasive urothelial carcinoma (transitional cell carcinoma) of the bladder as follows:
Patients must have pathologically confirmed non-muscle invasive bladder cancer (NMIBC) high grade disease (HG), as defined by the 2004 WHO classification system
Patients must have no evidence of muscle invasive disease
T1 patients need to have evidence of muscle included in their latest biopsy; and if not a re-TURBT has to be done prior to enrollment
Muscle invasive urothelial carcinoma of the bladder histologically confirmed at the enrolling institution; (urothelial carcinoma invading into the prostatic stroma with no histologic muscle invasion is allowed provided the extent of disease is confirmed via imaging and/or EUA)
History of another malignancy within 5 years prior to randomisation, except for either non- melanomatous carcinoma of the skin or, adequately treated, non-muscle-invasive urothelial carcinoma of the bladder (Tis, Ta and low grade T1 tumours).
Patients must have a histologically confirmed diagnosis of non- muscle invasive urothelial carcinoma of the bladder at the study institution prior to the beginning of the study; this includes patients with:\r\n* High grade Ta papillary lesion(s)\r\n* High or low grade T1 papillary lesion(s) \r\n* Carcinoma in situ (CIS), with or without Ta or T1 papillary tumor(s) of any grade
Histologically or cytologically confirmed non-muscle invasive bladder cancer [Ta, T1 or Tis (CIS)] that has been removed by transurethral resection
Neo-adjuvant therapy prior to baseline staging procedures for the current occurrence of non-muscle invasive bladder cancer
Muscle invasive urothelial carcinoma of the bladder histologically confirmed at Memorial Sloan Kettering Cancer Center (MSKCC) or participating site; (urothelial carcinoma invading into the prostatic stroma with no histologic muscle invasion is allowed, provided the extent of disease is confirmed via imaging and/or endoscopic ultrasonic aspiration [EUA])
Patients with worsening steroid myopathy (history of gradual progression of bilateral proximal muscle weakness, and atrophy of proximal muscle groups)
Initial histological diagnosis of muscle invasive urothelial carcinoma
Previous muscle-invasive (i.e., stage T2 or higher) transitional-cell carcinoma of the bladder
Histologically confirmed muscle invasive transitional cell carcinoma of the bladder at Memorial Sloan-Kettering Cancer Center (MSKCC); (Note: urothelial carcinoma invading into the prostatic stroma with no histologic muscle invasion is allowed, provided the extent of disease is confirmed via imaging and/or exam under anesthesia [EUA])
Histologically confirmed non-muscle-invasive transitional cell carcinoma (TCC) of the bladder with carcinoma in-situ (CIS)
Evidence of locally advanced, metastatic, muscle-invasive, and/or extravesical bladder cancer
Have a history of muscle invasive bladder cancer
Any subjects with muscle-invasive TCC (stages T2 - T4) OR any known TCC of the ureter or renal pelvis are not allowed
Presence of a muscle invasive bladder tumor(s) (T2), specific for transitional cell carcinoma on pre-operative histology (i.e. biopsy or transurethral resection of bladder tumor [TURBT]).
Patients only: must have a tumor in extremity muscle tissue or in the pelvis
Evidence of accessory respiratory muscle use with breathing
Patients who present to the urology clinic for non-muscle-invasive bladder cancer will be screened for participation in this pilot study (goal of 5 patients); patients who have completed transurethral resection of bladder tumor (TURBT) and are candidates for intravesical therapy are eligible for inclusion
Patients with evidence of muscle-invasion or metastatic disease will be excluded
Histological proof of muscle-invasive transitional cell carcinoma of the bladder (stage II-III). Subjects with evidence of metastatic nodal disease to the obuturator or presacral lymph nodes only may be included (N1 M0). Subjects with any degree of fixation of the pelvic sidewall are not eligible.
The subject is undergoing one of the following reconstructive procedures that requires latissimus dorsi muscle harvest: a. post-mastectomy breast reconstruction procedure (either nipple or skin sparing) in which a female subject needs additional muscle coverage over an implant, but does not need additional skin (i.e., patient is a candidate for a pedicled latissimus dorsi muscle flap procedure); b. scalp reconstruction procedure in which the subject needs a free latissimus dorsi muscle flap for wound coverage; c. upper extremity reconstruction procedure in which the subject needs a free latissimus dorsi muscle flap for wound coverage; or, d. lower extremity reconstruction procedure in which the subject needs a free latissimus dorsi muscle flap for wound coverage
At least one muscle spasm per day at time of screening
Muscle spasms onset after starting vismodegib
Presence of muscle spasms or active neurologic disease prior to start of vismodegib
Use of muscle relaxant medications such as cyclobenzaprine within four weeks of enrollment and during course of the study, unless the regimen of muscle relaxants is stable for 4 weeks prior to enrollment and does not change for the duration of the study
Male and female patients who present to the urology clinic for recurrent non-muscle invasive bladder cancer (NMIBC) or muscle invasive bladder cancer (MIBC) and are candidates for radical cystectomy will be screened for participation
Patients must have high risk non-muscle invasive urothelial bladder carcinoma (Tis, Ta high grade [HG], or T1) that is pathologically confirmed by the Memorial Sloan Kettering Department of Pathology or a documented history of TaHG or T1 non-muscle invasive urothelial bladder tumors
Patients found to require sternocleidomastoid muscle or internal jugular vein excision
Patients with a prior diagnosis of non-muscle invasive, ?T1, urothelial cell\n             carcinoma of the bladder scheduled to undergo surveillance cystoscopy.
Patients who have had a cystectomy or prior diagnosis of muscle invasive disease (T2\n             or greater)
Histologically confirmed muscle-invasive urothelial cancer of the bladder within 60 days of study enrollment\r\n* Patients must be willing to provide a TURBT specimen during screening and prior to enrollment if adequate specimen (formalin-fixed paraffin-embedded [FFPE] tissue block or 20 unstained slides) from initial TURBT documenting muscle-invasive urothelial bladder cancer is not available
Histologically documented urothelial carcinoma (squamous differentiation or mixed cell types allowed).
Must have a histologically confirmed transitional cell carcinoma (TCC, also known as urothelial carcinoma), locally advanced or metastatic
Histologically confirmed muscle-invasive urothelial carcinoma of the bladder or upper tract; variant histology allowed as long as urothelial carcinoma is predominant (> 50%); pure small-cell carcinoma is excluded
Patients must not have had urothelial carcinoma in the prostate or upper urinary tract within the previous 24 months, or muscle invasive urothelial carcinoma of the bladder at any time; patients must have a computed tomography (CT) or magnetic resonance imaging (MRI) of the abdomen and pelvis to rule out upper tract malignancy and intra-abdominal metastases within 90 days prior to registration
Patients must have histologically proven Ta, carcinoma in situ (CIS) or T1 stage urothelial cell carcinoma of the bladder within 90 days prior to registration
Histologically confirmed diagnosis of urothelial carcinoma of the bladder. Variant histology is acceptable if there is a predominant urothelial component.
Urothelial carcinoma
All subjects must have previously treated either locally advanced or metastatic renal or urothelial cell carcinoma to be eligible for participation
Urothelial carcinoma;
Bladder urothelial carcinoma
Adequately treated urothelial papillary non-invasive carcinoma or carcinoma in situ
Patients must have histologically proven urothelial carcinoma of the bladder; those with mixed histology, including a component of urothelial carcinoma, are eligible; pure small cell carcinoma, pure adenocarcinoma, and pure squamous cell carcinoma are excluded
Patients must not have received previous systemic cytotoxic chemotherapy for urothelial carcinoma
Concomitant upper tract urothelial carcinoma
Histologic evidence of urothelial carcinoma of the bladder
Low/intermediate-risk papillary urothelial carcinoma of the bladder, at initial occurrence or recurrent with > 6 months interval free of disease
Diagnosis of urothelial carcinoma involving the prostatic urethra or upper urinary tract
Patients must have histologically or cytologically confirmed urothelial tract carcinoma; patients with urothelial carcinoma of the bladder, upper tract, or urethra are eligible
Predominant histologic component (> 50%) must be urothelial (transitional cell) carcinoma
Localized urothelial cancer of bladder with presence of transitional cell carcinoma (TCC) component; mixed histologies are allowed
Biopsy taken from one or more tumors located above the ureteropelvic junction (UPJ) showing LG urothelial carcinoma. Diagnosed not more than 2 months prior to the screening.
Patient has a history of invasive urothelial carcinoma in the urinary tract during the past 5 (Five) years.
Patient has a history of high grade papillary urothelial carcinoma in the urinary tract during the past 2 (Two) years.
Evidence of non-bladder urothelial (transitional cell) carcinoma by biopsy, cytology, or radiological imaging within the past 2 years of treatment (e.g. upper tract transitional cell carcinoma, urethral urothelial carcinoma)
Histological or cytologically proven urothelial carcinoma; mixed urothelial/non-urothelial cell histologies are allowed but pure non-urothelial cell carcinoma is NOT allowed
Patient has ever had confirmed extravesical urothelial disease (upper tract and urethral including prostatic urethral)
Subjects must have a histologic diagnosis of urothelial carcinoma with radiologic, histologic or cytologic evidence of metastatic disease
Has positive urine cytology for urothelial malignancy at screening.
Adequately treated urothelial papillary noninvasive carcinoma or carcinoma in situ.
Muscle invasive (T2 or above) urothelial carcinoma or urothelial carcinoma outside the bladder
Histologically confirmed muscle-invasive urothelial carcinoma of the bladder defined as T2-T4 stage; mixed histologies are acceptable provided urothelial carcinoma is the predominant histology (? 50%); patients with > 50% non- urothelial carcinoma histologies or any component of small cell carcinoma are not eligible; resectable clinical node-positive (N1) patients are eligible provided the lymph nodes are confined to the true pelvis and are within the planned surgical lymph node dissection template
Patients with concurrent upper urinary tract (i.e. ureter, renal pelvis) invasive urothelial carcinoma; (NOTE: Patients with history of non-invasive [Ta, Tis] upper tract urothelial carcinoma that has been definitively treated with at least one post-treatment disease assessment [i.e. cytology, biopsy, imaging] that demonstrates no evidence of residual disease are eligible)
Patients must have histologic proof of urothelial cancer; this includes bladder cancer, in addition to other tumors of the urothelial lining including renal pelvis, ureteral, and urethral cancer; upper tract urothelial carcinoma will also be included; this group may include any patient requiring cystectomy, including muscle invasive disease (cT2-3aN0M0), whose tumor could not be completely removed at transurethral resection
Any evidence of metastatic urothelial carcinoma
PHASE I AND II SCLC AND UROTHELIAL CARCINOMA EXPANSION COHORT: Patients who are receiving any other investigational agents
UROTHELIAL CARCINOMA EXPANSION COHORT ONLY: Patients who have had prior treatment with olaparib or other camptothecin inhibitors
PHASE I AND II SCLC AND UROTHELIAL CARCINOMA EXPANSION COHORT: Hypersensitivity to study therapies and its excipients
PHASE I AND II SCLC AND UROTHELIAL CARCINOMA EXPANSION COHORT: Any chronic or concurrent acute liver disease
UROTHELIAL CARCINOMA EXPANSION COHORT: Prior antiangiogenic therapy are permitted (2-week washout from therapy is required)
UROTHELIAL CARCINOMA EXPANSION COHORT: ECOG 0–2
UROTHELIAL CARCINOMA EXPANSION COHORT: Leukocytes >= 3,000/mcL
Primary urothelial or predominantly urothelial carcinoma of the bladder
Has histologically confirmed urothelial carcinoma of the bladder; those with mixed histology, including a component of urothelial carcinoma, are eligible; pure small cell carcinoma, pure adenocarcinoma, and pure squamous cell carcinoma are excluded
Has had no prior systemic cytotoxic chemotherapy for urothelial carcinoma (prior intravesicular chemotherapies are permitted)
Has received prior radiation therapy to the bladder for the purpose of treating urothelial carcinoma
Evidence of upper tract urothelial carcinoma
Have locally advanced or metastatic urothelial cancer that is not amenable to curative surgical treatment\r\n* Have histologically or cytologically confirmed urothelial tract carcinoma
Pathologic diagnosis of urothelial or squamous cell carcinoma of the bladder
cT2/T3-N0-M0 urothelial carcinoma of the bladder
More than two prior lines of systemic anti-cancer therapy for urothelial carcinoma
Prior systemic chemotherapy for urothelial cell carcinoma of the bladder.
Absence of concomitant upper tract urothelial carcinoma (i.e. cancer within the kidney or ureter) as evidenced on computed tomography (CT) urogram and no visible lesion and/or biopsy proven evidence of urothelial carcinoma within the prostatic urethra (i.e. biopsy proven presence of cancer within the prostatic urethra)
Pathologically proven (either histologic or cytologic) diagnosis of urothelial carcinoma
Upper tract urothelial carcinoma
Patients must have histologically or cytologically confirmed metastatic urothelial carcinoma; urothelial cancer derived from the bladder, ureter or upper tract is permitted
Metastatic or inoperable urothelial cancer
Patients must have histologically confirmed urothelial carcinoma that is advanced or metastatic
Patients with active malignancies in addition to urothelial carcinoma
Absence of concomitant upper tract urothelial carcinoma or urothelial carcinoma within the prostatic urethra. Freedom from upper tract disease (if clinically indicated) as indicated by no evidence of upper tract tumor by either intravenous pyelogram, retrograde pyelogram, computed tomography (CT) scan with or without urogram, or MRI with or without urogram performed within 6 months of enrollment
History of malignancy of other organ system within past 5 years, except treated basal cell carcinoma or squamous cell carcinoma of the skin and ? pathological tumor-2 (pT2) upper tract urothelial carcinoma at least 24 months after nephroureterectomy. Also patients with genitourinary cancers other than urothelial cancer or prostate cancer that are under active surveillance are excluded (see inclusion criterion 9)
Patients must have histologically proven urothelial carcinoma of the bladder; those with mixed histology, including a component of urothelial carcinoma, are eligible; small cell carcinoma, pure adenocarcinoma, and pure squamous cell carcinoma are excluded
Patients must not have received previous systemic cytotoxic chemotherapy for urothelial carcinoma
Has received no prior systemic chemotherapy for advanced or metastatic urothelial carcinoma, with the following exceptions:
For urothelial carcinoma:
For RCC, urothelial carcinoma, and gastric or GEJ adenocarcinoma, hemoglobin ?8.0 g/dL
For urothelial carcinoma, prior treatment with any taxane
Concomitant bladder urothelial carcinoma is acceptable if it is organ confined and surgically resectable
Subjects with urothelial carcinoma:
Adequately treated urothelial papillary non-invasive carcinoma or carcinoma in situ
For Phase 2, subjects with the following tumor types who meet protocol-defined criteria: advanced or metastatic NSCLC, melanoma, urothelial carcinoma, SCCHN, SCLC, and CRC.
Patients with any component of small cell carcinoma are not eligible; other variant histologies are permitted provided the predominant (>= 50%) subtype is urothelial carcinoma
Patients must be able to provide a sufficient biopsy sample to the central pathologist for histopathologically confirmed, transitional cell (urothelial) carcinoma. Urothelial tumors with mixed histology (but with <50% variant) are eligible.
Any primary site of urothelial carcinoma including upper tract, renal pelvis, bladder, and ureters
Prior therapy with ? 1 systemic chemotherapy regimens for urothelial carcinoma
Pathologically proven diagnosis of carcinoma of the bladder within 105 days prior to registration\r\n* Operable patients whose initial tumor is a primary high grade urothelial carcinoma of the bladder exhibiting histologic evidence of invasion into the lamina propria (disease clinical stage T1) or a high grade stage Ta urothelial carcinoma without hydronephrosis; patients who have involvement of the prostatic urethra with urothelial carcinoma and have no evidence of stromal invasion of the prostate remain eligible; if the patient’s initial tumor was a high grade stage Ta urothelial carcinoma then his/her recurrent tumor must be a high grade stage T1 urothelial carcinoma to be eligible
Urothelial Carcinoma
The patient must have a pathologically confirmed diagnosis of urothelial BLC, which is currently Stage 4 disease.
A patient with urothelial carcinoma with variant histologic differentiation (e.g. squamous cell differentiation, glandular differentiation, neuroendocrine differentiation) will be eligible provided that the predominant histology is urothelial carcinoma.
Patient must have a diagnosis with urothelial carcinoma of the bladder with clinically apparent tumor Ta, G1-G2.
Patients must have histologically-proven (T2, T3, or T4a) urothelial carcinoma of the bladder (UCB) that requires primary radical cystectomy for definitive treatment; patients must not have clinical stage consistent with a low-risk of node metastasis (carcinoma in situ [CIS] only, T1); patients with a T4b (fixed lesion) are not eligible for this study; NOTE: Patients with predominant urothelial carcinoma with elements of adenocarcinoma, squamous cell carcinoma, micropapillary or minor components of other rare phenotypes are eligible; patients with predominantly small cell, squamous cell, or adenocarcinoma histologies are not eligible; patients with other non-urothelial cancers are not eligible (e.g., sarcoma, lymphoepithelial, nested variant); clinical stage is based on all of the following: transurethral resection of bladder tumor(s) (TURBT[s]) that determined the need for cystectomy, bimanual exam and cross sectional imaging
Patients must have histologically or cytologically confirmed urothelial tract carcinoma
Histologically or cytologically confirmed urothelial carcinoma.
Patients must have undergone a radical cystectomy (reconstructed urinary diversion may be non-continent diversions (eg, ileal conduits) or continent non-orthotopic catheterizable diversions (eg, Indiana pouch) or continent orthotopic diversions (eg, Studer pouch or neobladder) for urothelial bladder carcinoma within 105 days prior to registration; final cystectomy pathology must be either pure urothelial carcinoma or dominant urothelial carcinoma with admixture of other histologies excluding small cell variants\r\n* Neoadjuvant (preoperative) or adjuvant (postoperative) chemotherapy for the bladder cancer is permitted; however, all patients, even those who will receive adjuvant chemotherapy must be registered within 105 days after completing cystectomy regardless of whether adjuvant chemotherapy has started; patients who will then receive adjuvant (postoperative) chemotherapy will be randomized within 28 days of completing chemotherapy
Diagnosis of urothelial carcinoma
Participants must have received prior systemic chemotherapy treatment for metastatic urothelial carcinoma. NOTE: Up to 2 prior systemic chemotherapeutic regimens given in the metastatic disease setting for urothelial carcinoma are allowed.
Histologically proven recurrent urothelial carcinoma of the bladder or prostatic urethra, Stage Tis, Ta
Pure small cell histologic variant or other pure non-urothelial carcinomas
Prior systemic chemotherapy for transitional cell carcinoma of the bladder. Any other prior systemic chemotherapy for a non-urothelial carcinoma must have been completed > 5 years prior to initiation of study.
Any male or female patient diagnosed with incident or recurrent Urothelial Cell Carcinoma and undergoing surveillance at 3 month intervals.
Has had all urothelial cell carcinoma tumor resected within the past 12 months
Planning to undergo radical cystectomy or chemotherapy-radiation for Urothelial Cell Carcinoma
Must have diagnosis of urothelial cancer
Histologic or imaging evidence of urothelial carcinoma of the bladder
Urothelial cancer.
Malignancies other than urothelial carcinoma within 5 years prior to Cycle 1, Day 1
Clinical stage T2-T4a, N0, M0 urothelial bladder cancer