Participants must discontinue use of the following agents within 7 days prior to therapy\r\n* Strong CYP3A4 inhibitors that treat HIV\r\n* Other strong CYP3A inhibitors\r\n* Moderate CYP3A4 inhibitors should be used with caution but are not excluded; if 2 moderate CYP3A4 inhibitors are used concurrently, one must be discontinued at least 7 days (1 week) prior to the initiation of chemotherapy\r\n* P-glycoprotein inhibitors\r\n* If patients are taking any of these excluded medications, they must be discontinued at least 7 days (1 week) prior to the initiation of chemotherapy\r\nAll concomitant medications must be reviewed by the study chair or co-chair prior to enrollment by email; because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference for a list of drugs to avoid or minimize use of
Patients must not be taking, nor plan to take while on protocol treatment, strong CYP3A4 inhibitors (e.g. boceprevir, cobicistat, danoprevir, elvitegravir/RIT, fluvoxamine, indinavir, itraconazole, ketoconazole, lopinavir/RIT, nefazodone, nelfinavir, posaconazole, ritonavir, telaprevir, telithromycin, tipravavir/RIT, or voriconazole); strong CYP3A4 inducers (e.g. avasimibe, phenytoin, rifampin, rifabutin); potent inhibitors of CYP1A2 (e.g. ciprofloxacin); and/or drugs known to be CYP3A4 substrates with a narrow therapeutic range (e.g., diergotamine, ergotamine) within 14 days prior to randomization; moderate inhibitors or inducers of isoenzyme CYP3A4 should be avoided, but if necessary can be used with caution
Concomitant medications\r\n* Chronic concomitant treatment with strong CYP3A4 inducers or CYP3A4 inhibitors is not allowed; patients must discontinue the drug at least 14 days prior to study registration\r\n* Chronic concomitant treatment with CYP1A2 substrate is not allowed; patients must discontinue the drug at least 14 days prior to study registration
Treatment with clinically significant metabolic CYP3A inducers within 14 days before the first dose of study drug; clinically significant CYP3A inducers are not permitted during the study
Current use or anticipated need for food or medications that are known strong CYP3A4 inhibitors/inducers, including their administration within 7-days prior to the first gedatolisib (PF-05212384) or palbociclib dose and during study treatment
Concomitant treatment with strong inhibitors or inducers of CYP3A4, CYP2C9 and CYP2C19.
Strong CYP3A4 and CYP2C8 inhibitors or inducers or CYP3A4 substrate drugs with a narrow therapeutic range taken within 14 days or 5 drug half-lives before start of study drug.
Currently receiving medications known to be inhibitors of CYP3A4/5. Subjects currently receiving medications of known inducers of CYP3A4/5 or substrates of CYP2C8/9 and CYP1A2 may be excluded.
Inclusion Criteria for all Modules:\n\n          1. Metastatic MIBC\n\n          2. 2nd/3rd line\n\n          3. Failed adjuvant/neo-adjuvant chemotherapy <1 yr\n\n          4. 1 lesion ?10 mm at baseline in the longest diameter suitable for accurate repeated\n             measurement\n\n          5. WHO perf. status 0-1\n\n        For Module A:\n\n          1. M/F ?25\n\n          2. Confirmation of FGFR3 mutation or FGFR fusion\n\n        For Module B:\n\n          1. Hgb ?10 g/dL\n\n          2. Deleterious mutation, deletion or truncation in any HRR genes\n\n        For Module C:\n\n        1. Tumour harbours a deletion or inactivating mutation of the CDKN2A or RB1 genes and/or\n        amplification of CCNE1, MYC, MYCL or MYCN genes\n\n        For Module E:\n\n        1. Contraception must be sustained throughout treatment with vistusertib and 16 wks after\n        last dose\n\n        For Module F:\n\n          1. Adequate organ and marrow function, defined as Leukocytes ?3.0x10(exp9)/L; ANC\n             ?1.5x10(exp9)/L; platelets ?100x10(exp9)/L\n\n          2. Contraceptive measures must be sustained throughout treatment with AZD9150 and for 180\n             days after the last dose.\n\n        Exclusion Criteria for all Modules:\n\n          1. Immunotherapy, chemotherapy, anticancer agents, radiotherapy <4 wks, or radiotherapy\n             for palliation <2 wks, any study drugs <30 days.\n\n          2. Major surgery <4 wk\n\n          3. Unresolved toxicities from prior therapy\n\n          4. Concurrent chemotherapy, immunotherapy, biologic or hormonal therapy\n\n          5. Immunosuppressive drugs <28 days\n\n          6. Any of the following: Autoimmune disease ?2 yr; IBD; primary immunodeficiency; organ\n             transplant requiring immunosuppressives\n\n          7. Spinal cord compression or brain metastases, treated and stable & not requiring\n             steroids for at least 4 weeks\n\n          8. Severe or uncontrolled systemic disease\n\n          9. Any of the following: Mean QTc ?470 ms; abnormalities in resting ECG; factors that\n             increase the risk of QTc prolongation or arrhythmia; uncontrolled hyper/hypotension;\n             LVEF <55%; atrial fibrillation; NYHA Grade II-IV; severe valvular disease;\n             uncontrolled angina; stroke/TIA <6 months; acute coronary syndrome <6 months\n\n         10. Any of the following laboratory values: ANC <1.5x10(exp9)/L; Platelets\n             <100x10(exp9)/L; Hgb <9.0 g/dL; ALT >2.5xULN or >5xULN with liver mets; Total\n             bilirubin >1.5 times ULN or with Gilbert's disease ?2×ULN; Creatinine >1.5xULN\n             concurrent with creatinine clearance <50 mL/min; Corrected Ca >ULN, PO4 >ULN\n\n         11. Active infection including tuberculosis, hepatitis B (HBV), hepatitis C (HCV), or\n             human immunodeficiency virus. Patients with a past or resolved HBV infection are\n             eligible. Patients positive for HCV antibody are eligible only if polymerase chain\n             reaction is negative for HCV RNA.\n\n         12. Live attenuated vaccination <30 days\n\n        For Module A:\n\n          1. Prior exposure to: Nitrosourea or mitomycin C <6 weeks; any agent with FGFR inhibition\n             as its primary pharmacology; AZD4547; potent inhibitors/inducers of CYP3A4, inhibitors\n             of CYP2D6 or substrates of CYP3A4 <2 wks\n\n          2. Ophthalmological criteria: RPED; laser treatment or intraocular injection for macular\n             degeneration; age-related macular degeneration; retinal vein occlusion; retinal\n             degenerative disease; other clinically relevant chorioretinal defect\n\n          3. Refractory nausea/vomiting, chronic GI diseases, or previous bowel resection\n\n        For Module B:\n\n          1. Transfusion <120 days\n\n          2. Concurrent medications that are strong inhibitors of cytochrome P450 (CYP) 3A (CYP3A)\n             or strong inducers of CYP3A4.\n\n          3. Previous treatment with PARP inhibitor, including olaparib\n\n          4. Patients with history of MDS or AML\n\n        For Module C:\n\n          1. Prior exposure to any of the following: Nitrosourea or mitomycin C <6 wks; any agent\n             with Wee1 inhibition as its primary pharmacology; prior treatment with AZD1775\n\n          2. Any drugs or products known to be sensitive to CYP3A4 substrates or CYP3A4 substrates\n             with narrow therapeutic index, or moderate to strong inhibitors/inducers of CYP3A4\n\n          3. Herbal preparations\n\n          4. Refractory nausea and vomiting or chronic GI diseases\n\n          5. Cardiac disease <6 months\n\n        For Module E:\n\n          1. Minor surgery <14 days of first dose\n\n          2. Exposure to specific substrates of OATP1B1, OATP1B3, MATE1 and MATE2K <5x half-life\n             before treatment. Exposure to strong/moderate inhibitors/inducers of CYP3A4/5, Pgp\n             (MDR1) and BRCP if taken within washout periods before the first dose\n\n          3. Haemopoietic growth factors (filgrastim, sargramostim, GM-CSF) <14 days prior to\n             treatment\n\n          4. Other mTOR inhibitors\n\n          5. Renal disease or renal tubular acidosis\n\n          6. Uncontrolled Type 1 or 2 diabetes\n\n        For Module F:\n\n        1. AST ? 2.5xULN or ?5xULN with liver mets
Co-administration with strong inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole, ritonavir) or P-glycoprotein (PgP) is prohibited; co-administration with moderate CYP3A4 inhibitors (e.g., erythromycin, fluconazole) or PgP inhibitors may be used with caution and everolimus dosing must be discussed with principle investigator (PI) at the time of enrollment
The following medications are contraindicated or must be used with caution\r\n* Contraindicated:\r\n** Cytochrome P450, family 2, subfamily C, polypeptide 8 (CYP2C8) strong and moderate inhibitors\r\n** CYP2C8 inducers\r\n** Cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) strong and moderate inhibitors\r\n** CYP3A4 inducers\r\n** CYP3A4 sensitive substrates\r\n* Exclusions: the following supportive care medications will be allowed will be allowed as they are routinely administered with carboplatin and paclitaxel and have no potential interaction with talazoparib (BMN 673): dexamethasone, aprepitant, fosaprepitant, and ondansetron); oral pain medications such as hydrocodone, oxycodone taken on an as needed basis are also permitted\r\n* Transdermal products designed for systemic delivery must be assessed for interaction potential; topical products not designed to provide systemic delivery (including inhaled products, ophthalmologic products and transvaginal preparations) do not need to be considered\r\n* Other contraindicated medications (per above) are not allowed unless close monitoring with labs or drug levels or by symptoms with subsequent dose adjustments is feasible; patients taking these concurrent medications are ineligible unless they can discontinue or switched to alternative medications prior to initiation of the study drug (at least 5 half-lives)\r\n* Use with caution:\r\n** CYP2C8 sensitive substrates\r\n** CYP2C8 weak inhibitors\r\n** CYP3A4 non-sensitive substrates\r\n** CYP3A4 weak inhibitors\r\n* These agents may be permitted if discontinuation is not feasible and no acceptable alternatives are available as determined by the treating physician; however, caution should be used; consider monitoring with labs or drug levels or by symptoms and consider dose adjustments of the medication
Patients who are currently receiving treatment with drugs known to be strong inhibitors or inducers of isoenzyme CYP3A4 including herbal medications; Note: if a medication is incorrectly documented as prohibited in this protocol, documentation from the site pharmacist to the contrary will be acceptable for the purposes of registration
Participant has received the following within 7 days prior to the first dose of study drug: corticosteroid therapy, CYP3A inhibitors, CYP3A inducers.
Subjects using agents known to inhibit or induce CYP3A4, such as ketoconazole, itraconazole, erythromycin, or rifampin, within 7 days prior to study start
Treatment with strong inhibitors and/or inducers of CYP3A4, CYP2C9, or CYP2C19 within 7 days preceding the first dose of the study drugs.
Patient receiving treatment with medications that either strong inducers or inhibitors of CYP2C8 or CYP3A4/5, or patients receiving medication that prohibits proton pump inhibitors and that cannot be discontinued at least 1 week prior to start of treatment and for the duration of the study.
Mifepristone can both inhibit CYP3A4 and induce CYP3A4; addition of mifepristone to a pre-existing drug regimen may cause a mild and temporary increase in plasma drug concentration of drugs with significant CYP3A4 metabolism; medications that are strong inducers of CYP3A4 such as carbamazepine, oxcarbazepine, phenobarbital, phenytoin, primidone, rifabutin, rifampin, rifapentine, St. John's wort may decrease plasma mifepristone levels; strong CYP3A4 inhibitor medications are expected to cause the largest increases in plasma mifepristone concentrations\r\n* Mifepristone may increase the plasma drug concentration of concomitant medications with metabolism mediated by CYP2C9/CYP2C8; drugs with the largest increases will be those whose metabolism is largely or solely mediated by CYP2C9/2C8 and include: non-steroidal anti-inflammatory drugs (NSAIDs) and warfarin
Subject takes cytochrome P450, family 3, subfamily A (CYP3A) inhibitors within 3 days or inducers within 7 days prior to the study drug administration; any questions or clarifications of these determinations should be brought to the attention of the principal investigator (PI); the PI will make the final determination on when it is safe to initiate ABT-348 (ilorasertib) therapy under circumstances where the magnitude or relevance of possible CYP3A4 inhibitors/inducers is unclear in the protocol appendix
While not an exclusion criterion, unless clinically indicated, patients should avoid taking other additional non-study medications that may interfere with the study medications; in particular, patients should avoid medications that are known to either induce or inhibit the activity of hepatic microsomal isoenzymes CYP1A2, CYP2C19 and CYP3A4
Cobimetinib is metabolized by the hepatic cytochrome P3A4 (CYP3A4) enzyme. Drugs CYP3A4/5 inhibitors and inducers should be avoided Atezolizumab-Specific Exclusion Criteria (Cohorts II and III Only)
Concomitant use of CYP3A4 inhibitors
Use of medications that are mainly metabolized by CYP3A4/5 or CYP2C9 that cannot be discontinued at least 1 week prior to start of treatment with LDK378 and for the duration of the study.
Other medications:\r\n* Patients receiving other anti-neoplastic agents are excluded\r\n* Patients on enzyme-inducing anticonvulsive agents are excluded\r\n* Patients requiring strong CYP3A4 or PGP inducers or inhibitors are excluded\r\n* Patients requiring anticoagulation or with uncontrolled bleeding are excluded\r\n* Patients on steroids for symptom management must be on a stable dose for 7 days prior to start of treatment
The following medications may significantly increase the level of pirfenidone and should not be taken concurrently including: fluvoxamine, ciprofloxacin > 500 mg twice daily, systemically administered aminolevulinic acid, vemurafenib and enoxacin, any other strong inhibitors of P450 isozymes CYP1A2, CYP2C9, 2C19, 2D6, and 2E1 should be avoided
Taking any medications or herbal supplements that are known to be strong inhibitors of CYP3A4 within at least 14 days before the first dose of ponatinib in patients with newly diagnosed only.
Mifepristone can both inhibit CYP3A4 and induce CYP3A4; addition of mifepristone to a pre-existing drug regimen may cause a mild and temporary increase in plasma drug concentration of drugs with significant CYP3A4 metabolism; medications that are strong inducers of CYP3A4 such as carbamazepine, oxcarbazepine, phenobarbital, phenytoin, primidone, rifabutin, rifampin, rifapentine, St. John's wort may decrease plasma mifepristone levels; strong CYP3A4 inhibitor medications are expected to cause the largest increases in plasma mifepristone concentrations\r\n* Mifepristone may increase the plasma drug concentration of concomitant medications with metabolism mediated by CYP2C9/CYP2C8; drugs with the largest increases will be those whose metabolism is largely or solely mediated by CYP2C9/2C8 and include: non-steroidal anti-inflammatory drugs (NSAIDs) and warfarin
Cabozantinib is metabolized by CYP3A4; the metabolism and consequently overall pharmacokinetics of cabozantinib could be altered by inhibitors and/or inducers or other substrates of CYP3A4; it is recommended that chronic concomitant treatment with strong CYP3A4 inhibitors (eg, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, and St. John’s wort) or inducers should be avoided; if patients are taking any strong CYP3A4 inhibitors, alternate medications with no or minimal CYP3A4 inhibitors should be sought prior to trial enrolment; while mild inhibitors/inducers of these cytochrome P450 isoenzymes are not specifically excluded, investigators should be aware that cabozantinib exposure may be altered by the concomitant administration of these drugs, and avoidance is also recommended
Concomitant use of CYP3A4 inhibitors
Taking any medications or herbal supplements that are known to be strong inhibitors of CYP3A4 within at least 14 days before the first dose of ponatinib.
Drugs that potently inhibit or induce CYP3A4 should be administered with caution
Concurrent use of CYP3A4 inhibiting or activating medications
Concomitant use of CYP3A4 inhibitors
While not an exclusion criterion, unless clinically indicated, patients should avoid taking other additional non-study medications that may interfere with the study medications; in particular, patients should avoid medications that are known to strong inhibitor or inducers of hepatic microsomal isoenzymes CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP3A4/5, UGT1A1, UGT1A3 and transporters BCRP and P-gp
Concomitant use of cytochrome P450 (CYP3A4) inhibitors or inducers is allowed but should be monitored closely for the use of strong inhibitors and/or inducers; patient is strongly advised to avoid grapefruit or grapefruit juice and herbal supplements with high risk of interaction with CYP3A4 or CYP2C8, such as St. John’s Wort while on study
Patient has had prescription or non-prescription drugs or other products (ie, grapefruit juice) known to be moderate to strong inhibitors or inducers of CYP3A4, which cannot be discontinued 14 days before day 1 of dosing and withheld throughout the study until 14 days after the last dose of AZD1775; co-administration of aprepitant and fosaprepitant during this study is prohibited; co-treatment with weak inhibitors of CYP3A4 is allowed
Use of CYP3A4 inhibitors or inducers and CYP2D6 substrates must be discontinued prior to study entry
Planned ongoing treatment with other drugs thought to potentially have adverse interactions with either of the medications included in the study treatment, for example:\r\n* Alpha 1-blockers\r\n* Vasodilators, such as nitrates\r\n* Other PDE5 inhibitors, eg, vardenafil, tadalafil\r\n* Therapeutic anticoagulation with vitamin K antagonists (eg, warfarin), heparins and heparinoids, or direct thrombin inhibitors (DTIs)\r\n** Note: prophylactic low-dose anticoagulation to maintain vascular access devices or low-dose daily aspirin for cardiac health is permitted\r\n* Immunosuppressants such as tacrolimus, leflunomide or tofacitinib, roflumilast, pimecrolimus\r\n** Note: administration of steroids as part of symptom management or for other supportive care purposes is permitted\r\n* STRONG CYP3A4 inhibitors and/or STRONG CYP3A4 inducers; \r\n** Note: if such medications have been used, patients must have discontinued these agents >= 2 weeks prior to initiating study treatment
On medications which are CYP3A inhibitors.
Inability to discontinue a prescription or non-prescription drugs or other products known to be metabolized by cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4), or to inhibit or induce CYP3A4 prior to day 1 of dosing and to withhold throughout the study until 2 weeks after the last dose of study medication; medications of particular concern are the following inhibitors of CYP3A4: azole antifungals (ketoconazole itraconazole, fluconazole and voriconazole), macrolide antibiotics (erythromycin, clarithromycin), cimetidine, aprepitant, human immunodeficiency virus (HIV) protease inhibitors, nefazodone and the following inducers of CYP3A4: phenytoin, barbiturates and rifampicin; substrates of CYP3A4 include statins (lovastatin, simvastatin, atorvastatin), midazolam, terfenadine, astemizole, and cisapride
Patients must not have received: cytochrome P450 3A4 (CYP3A4) inhibitors within seven (7) days prior to registration on protocol and for the duration of the study; however, amiodarone, another CYP3A4 inhibitor, should have been discontinued 6 months prior to registration and for the duration of the study
Patient must not have received: CYP3A4 inducers within fourteen (14) days prior to registration and for the duration of the study
Concurrent use of medications/food which may interfere with BMS-813160 including any strong inhibitors or inducers of CYP3A4 or P-gp is not allowed. These include but are not limited to class I antiarrhythmics (eg, quinidine, procainamide, disopyramide, lidocaine, phenytoin, mexiletine, tocainide, flecainide, propafenone, moricizine), grapefruit and seville oranges
Concomitant administration with strong inhibitors or inducers of CYP3A4 should be avoided; it is important to regularly consult a frequently-updated medical reference for a list of drugs to avoid or minimize use of
Current use of a prohibited medication or planned use of any forbidden medications during treatment with GSK525762 and abiraterone/enzalutamide. This includes medications with significant risk of Torsades de pointes as well as those that are potent inducers or inhibitors of CYP3A4 enzymes or strong inhibitors of CYP2C8.
Participants receiving any medications or substances that have antiviral activity against KSHV or that are strong inhibitors or inducers of cytochrome P450, family 3, subfamily A (CYP3A) or cytochrome P450, family 2, subfamily C, polypeptide 19 (2C19) are ineligible; each ART regimen must be reviewed by the PI before determining eligibility to receive nelfinavir mesylate (NFV); sensitive substrates should be avoided; of the antiretroviral drugs, only delaviridine, nevirapine, cobicistat-boosted antiretrovirals (strong CYP3A4 inhibitor), maraviroc (sensitive CYP3A4 substrate), and PIs (strong CYP3A4 inhibitor) are excluded; the following drugs are also prohibited:\r\nStrong Inhibitors of CYP3A4:\r\n* Antibiotics: clarithromycin, erythromycin, telithromycin, troleandomycin\r\n* HIV: non-nucleoside reverse transcriptase inhibitors (delaviridine, nevirapine), protease inhibitors (ritonavir, indinavir, lopinavir/ritonavir, saquinavir), cobicistat-boosted antiretrovirals (e.g., elvitegravir); NOTE: Clinical trials have demonstrated that there are no clinically significant drug-drug interactions between nelfinavir and the following antiretrovirals: efavirenz (strong CYP3A4 inhibitor), etravirine (strong CYP3A4 inhibitor); therefore, these antiretrovirals will not be excluded\r\n* Antifungals: itraconzaole, ketoconazole, voriconazole, fluconazole, posaconazole\r\n* Antidepressants: nefazodone\r\n* Antidiuretic: conivaptan\r\n* GI: cimetidine, aprepitant\r\n* Hepatitis C: boceprevir, telaprevir\r\n* Miscellaneous: seville oranges, grapefruit, or grapefruit juice and/or pummelos, star fruit, exotic citrus fruits, or grapefruit hybrids\r\nStrong Inducers of CYP3A4:\r\n* Glucocorticoids: cortisone (> 50 mg), hydrocortisone (> 40 mg), prednisone (> 10 mg), methylprednisolone (> 8 mg), dexamethasone (> 1.5 mg)\r\n* Anticonvulsants: phenytoin, carbamazepine, primidone, phenobarbital and other enzyme inducing anti-convulsant drugs (EIACD)\r\n* Antibiotics: rifampin (rifampicin), rifabutin, rifapentine\r\n* Miscellaneous: St. John’s Wort, modafinil\r\nStrong Inhibitors of CYP2C9:\r\n* Antifungals: fluconazole; lists including medications and substances known or with the potential to interact with the CYP3A or 2C19\r\nDrugs with KSHV antiviral activity:\r\n* Participants receiving any medications or substances that may interfere with KSHV replication are ineligible\r\nBecause the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated list; medical reference texts such as the physicians’ desk reference may also provide this information; as part of the enrollment/informed consent procedures, the participant will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the participant is considering a new over-the-counter medicine or herbal product; lists include medications and substances known or with the potential to interfere with KSHV replication
Consumption of agents which strongly inhibit CYP3A4 enzyme, within 7 days prior to the first dose of study treatment and during the study.
Consumption of agents which strongly induce CYP3A4 enzyme, within 14 days prior to the first dose of study treatment and during the study.
Patients currently receiving medications or herbal supplements of the classes below are ineligible; patients are eligible if they stop use of these compounds at least 1 week prior to receiving any treatment on this protocol\r\n* Potent inhibitors or inducers of CYP3A4 /5 (CYP3A4 inhibitors such as ketoconazole and clarithromycin are not allowed 7 days prior to the first dose of navitoclax and during navitoclax administration)\r\n* Strong or moderate inhibitors of Pgp or BRCP1 \r\n* Sensitive substrates of CYP2C9 (i.e. phenytoin and warfarin)\r\n* Substrates of certain drug transporters (OATP1B1, OATP1B3, MATE1 or MATE2K)
The patient is receiving medications that are:\r\n* Drugs which are exclusively or primarily eliminated by cytochrome P-450 isozyme 3A4 (CYP3A4)\r\n* Drugs which are exclusively or primarily eliminated by UDP-glucuronyl transferase 1A1 (UGT1A1)\r\n* Drugs which are substrates for the drug transporter multidrug resistance protein 1 (MDR1) have a narrow therapeutic window; or which are strong inhibitors of drug transporter MDR1\r\n** Patients should have discontinued strong CYP1A2 inhibitors (e.g. ciprofloxacin and fluvoxamine) at least five half-lives before beginning study treatment
Concomitant administration with strong inhibitors or inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) should be avoided; because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference for a list of drugs to avoid or minimize use of; ongoing phenytoin should be either discontinued if clinically safe or transitioned to non-enzyme-inducing antiepileptics like levetiracetam with a 8-day washout period (half-life 18-22 hours, time to steady-state 4-8 days) prior to first dose of VX-970 (7-days prior to WBRT)
Concomitant administration with strong inhibitors or inducers of CYP3A4 should be avoided; it is important to regularly consult a frequently-updated medical reference for a list of drugs to avoid or minimize use of
Has current use (within 7 days of randomization) or anticipated need for treatment with drugs or foods that are known strong cytochrome P450 (CYP3A4/5) inhibitors.
Taking any medication known to moderately or severely inhibit the CYP3A4 isozyme or any drugs that are CYP3A4 inducers (including anti-epileptic agents such as phenytoin). A stable regimen (? 4 weeks) of antidepressants of the SSRI class is allowed (common SSRIs include escitalopram oxalate, citalopram, fluvoxamine, paroxetine, sertraline, and fluoxetine)
Patients on medications known to alter cytochrome P450 3A4 (CYP3A4)
The MMAE component of glembatumumab vedotin is primarily metabolized by CYP3A. Patients taking strong CYP3A inhibitor and inducers are excluded in Phase I (the dose escalation portion), to minimize the effect of these modulators on exposure, tolerability and dose selection.
Patients who are currently receiving treatment (within 7 days prior to starting study treatment) with strong and moderate inhibitors or inducers of CYP3A4/5, substrates of CYP3A4/5 with a narrow therapeutic index or Herbal preparations/medications (Refer to Section 6.4 and Appendix 3) Inclusion Criteria Exceptions for Phase Ib Dose Expansion patients: Dose Expansion part of the study has 3 groups, following are the Inclusion Criteria exceptions for these 3 groups
Requirement for concomitant medications that strongly induce or inhibit CYP3A4/5
RP2D cohort subjects: contraindications to midazolam, any other midazolam within 7 days, or any medications or supplements known to be strong CYP3A inhibitors within 7 days or inducers within 12 days
Patients taking a known moderate to potent inhibitor of CYP1A2 are excluded; pomalidomide is primarily metabolized by CYP1A2 and CYP3A; pomalidomide is also a substrate for permeability (P)-glycoprotein (P-gp)
Concomitant use of significant CYP3A4 inhibitors unless able to be switched to a non-CYP3A4 inhibiting medication\r\n* Caution should be used when administering study drugs to patients taking medications significantly metabolized by these enzymes; particular attention should be paid to patients receiving warfarin; patients should have coagulation parameters monitored regularly, and warfarin dose adjusted accordingly; if these drugs cannot be discontinued or replaced, enrollment may be allowed after discussion with MSK principle investigator (PI)
Patients must not be taking medications that are inducers or inhibitors of CYP3A4; if previously on such an agent, the patient must be off of it for at least two weeks prior to study treatment
Unable or unwilling to discontinue use of strong inducers and inhibitors of CYP450 listed for at least 14 days prior to the first dose of study drug and for the duration of the study; CYP3A4 substrates can be administered, but investigators will need to be aware of possible increased or decreased effectiveness of the non-study drug and this should be recorded in concomitant medications; breast cancer resistance protein (BCRP) and p glycoprotein (PgP) inducers should be used with caution if another alternative drug is not able to be used\r\n* Note: If a medication is incorrectly documented as prohibited in this protocol, documentation from the site pharmacist to the contrary will be acceptable for the purposes of registration
Unable or unwilling to discontinue use of inducers and inhibitors of cytochrome P450 (CYP450) and breast cancer resistance protein (BCRP) and permeability glycoprotein (PgP) inducers and inhibitors listed in the protocol for at least 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of study drug and for the duration of the study; cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) substrates can be administered, but investigators will need to be aware of possible increased or decreased effectiveness of the non-study drug and this should be recorded in concomitant medications; dexamethasone is acceptable although listed as a CYP3A4 inducers/inhibitors as long as the dose is 16 mg/day or lesser
Patients who previously received CYP3A4 inducers or inhibitors must have discontinued these medications within at least 1 week prior to study entry and can re-start them 1 week post-operatively (or earlier if determined to be of clinical benefit, as determined by the treating physician)
Concomitant use of significant CYP3A4 inhibitors unless able to be switched to a non-CYP3A4 inhibiting medication without risk of worsening underlying condition and able to meet all other inclusion criteria
Patients taking substrates, inhibitors, or inducers of CYP3A4 should be encouraged to switch to alternative drugs whenever possible
Currently taking medication that is substantially metabolized by cytochrome P450 (CYP) 1A2 or CYP3A4 or taking medication known to be strong inhibitors or inducers of CYP3A4
Current (including their administration within 3 days prior to study entry) use or anticipated need for food or drugs that are strong CYP3A4 inhibitors.
Subject uses medication known to be strong inducers of CYP3A4 and CYP2C8 (Section 9.2).
Patients receiving treatment with medications that are known to be 1) strong inhibitors or inducers of CYP3A4/5; 2) CYP2C9 substrate with narrow therapeutic index; 3) QT prolonging agents; 4) proton pump inhibitors unless these medications can be discontinued at least a week prior to start of treatment.
Taking any medication known to inhibit the CYP3A4 isozyme or any drugs that are CYP3A4 inducers (including phenytoin), or any drugs associated with torsades de pointes or known to prolong the QTc(f) interval within 2 weeks prior to Day 1 of treatment on study. A stable regimen of antidepressants of the SSRI class is allowed
Patients must discontinue any medication that causes a strong CYP3A4 inhibition 1 week prior to treatment initiation; patients who are not able to discontinue these drugs are considered ineligible
Cytochrome P450 CYP3A4 inducers and inhibitors within 4 weeks prior to day 1
Current treatment with medications or consuming foods that are strong inhibitors or inducers of CYP3A4/5 or herbal medications and that cannot be discontinued at least one week prior to the start of treatment.
Contraindicated treatments noted in the product labelling for doxorubicin, including trastuzumab and inhibitors and inducers of CYP3A4, CYP2D6, or P-gp.
Treatment with inducers of cytochrome P450 3A4 (CYP3A4) within 7 days prior to first dose of study treatment
Patients taking CYP3A4 inducers or inhibitors are not eligible since it is not known whether the study drug is metabolized through this pathway. The following CYP3A4 inhibitors/inducers are not permitted during the trial - the azole antifungal - fluconazole, erythromycin, phenobarbital, verapamil.
Administration of cytochrome P450 CYP3A4 inducers and inhibitors within 4 weeks before day 1 and during the study
Treatment with CYP3A inducers within 14 days before the first dose of MLN4924. Treatment with CYP3A inhibitors within 14 days before the first dose of MLN4924; however, voriconazole and fluconazole need only be stopped for 3 days before MLN4924. Patients must have no history of amiodarone use in the 6 months before the first dose of MLN4924
Treatment with strong inducers or inhibitors (medications and herbal supplements) of cytochrome P450 3A4/5 (CYP3A4/5), or CYP3A4/5 substrates with a QT prolongation risk that cannot be discontinued at least 7 half-lives (or if the half-life is unknown,14 days) prior to study drug treatment.
Treatment with CYP3A inducers within 14 days before the first dose of MLN4924
Current or recent (within 6-months) use of fibric acid derivatives, lipid-modifying doses of niacin, cyclosporine or strong CYP3A4 inhibitors (i.e. clarithromycin, HIV protease inhibitors, and itraconazole)
Patients receiving treatment with medications that are known to be strong inhibitors or inducers of CYP3A4/5 or are metabolized by CYP2B6 and CYP2C9, that have narrow therapeutic indices that cannot be discontinued at least 2 weeks before first dose of study treatment and for the duration of the study
Unable or unwilling to discontinue use of strong inducers and inhibitors of CYP450 for at least 14 days prior to the first dose of study treatment and for the duration of the study; CYP3A4 substrates can be administered, but investigators will need to be aware of possible increased or decreased effectiveness of the non-study drug and this should be recorded in concomitant medications; BCRP and PgP inducers and inhibitors should be used with caution if another alternative drug is not able to be used; Note: as this list is constantly evolving, if a medication is incorrectly documented as prohibited in this protocol, documentation from the site pharmacist to the contrary will be acceptable for the purposes of registration
While not an exclusion criterion, unless considered clinically indicated, patients should avoid taking other additional non-study medications that may interfere with the study medication; in particular, patients should avoid medications that are known to either induce or inhibit the activity of hepatic microsomal isoenzymes CYP1A2, CYP2C19 and CYP3A4
Contraindicated: \r\n* CYP2C19 sensitive substrates (unless close monitoring with labs or drug levels with dose adjustments is feasible), inducers, and moderate/strong inhibitors of CYP2C19; patients taking these concurrent medications are ineligible unless they can be switched to alternative medications prior to initiation of the study\r\n* CYP3A4/5 inducers and moderate/strong inhibitors of CYP3A4/5; patients taking these concurrent medications are ineligible unless they can be switched to alternative medications prior to initiation of the study
Concomitant medications that are strong inhibitors of cytochrome P450 and CYP3A up to 14 days before Cycle 1 Day 1 (pimozide, diltiazem, erythromycin, clarithromycin, and quinidine, and amiodarone up to 90 days before)
Crolibulin is a substrate of cytochrome P450 (CYP)2C8, CYP2C9, CYP2C19 and CYP3A4; strong inducers and inhibitors of these enzymes will constitute concomitant medications that are prohibited during the study; these medications include but are not limited to: for CYP2C8, montelukast and trimethoprim, for CYP2C9, lovastatin and sertraline, for CYP2C19, fluoxetine, ketoconazole, pantoprazole, omeprazole, rabeprazole, and ticlopidine, for CYP3A4, itraconazole, clarithromycin, erythromycin, telithromycin, and verapamil
Patients may not be receiving agents thought to inhibit or induce the cytochrome p450 isoenzyme cytochrome P450 3A4 (CYP3A4)
Concomitant use of CYP3A4 inhibitors or inducers;
Require treatment with any known inducers and inhibitors of isoenzyme CYP3A
Patient currently using, or has previously used CYP3A4 inducers or inhibitors within 2 to 14 days prior to the initiation of oral therapy.
Concomitant use of CYP3A4 inhibitors
Taking any medications or herbal supplements that are known to be strong inhibitors of CYP3A4 within at least 14 days before the first dose of ponatinib
Patients taking substrates, inhibitors and inducers of CYP3A4 should be encouraged to switch to alternative drugs whenever possible, given the potential for drug-drug interactions with irinotecan
Patients who need to take CYP3A4 inducers, such as phenobarbital, dexamethasone, carbamazepine, phenytoin, rifampicin, or non-nucleoside reverse transcriptase inhibitors (e.g., efavirenz, nevirapine, etravirine) will be excluded; prior use of these agents is acceptable, as long as they are stopped at least a week prior to study entry
Current or anticipated need for drugs that are known cytochrome P450 isozyme CYP3A4 or CYP2C8 inducers or inhibitors; only exception is oral glucocorticoids, which are a required premedication for docetaxel
Medications or supplements that are known to be moderate reversible inhibitors of CYP3A within 5 times the inhibitor half-life (if a reasonable half-life estimate is known) or within 7 days (if a reasonable half-life estimate is unknown) before the first dose of study drugs. In general, the use of these agents is not permitted during the study for this combination except in cases in which an AE must be managed. See a list of nonexhaustive moderate CYP3A reversible inhibitors based on the US FDA Draft DDI Guidance.
Clinical requirement for medications that are concurrent inducers or inhibitors of CYP3A4; CYP3A4 substrates are allowed
Use of any drugs or substances known to be inducers of CYP3A4 enzymes within 4 weeks prior to Day 1 or planned to be used during the overall study period.
Women currently taking strong cytochrome P450 family 3 subfamily A member 4 (CYP3A4) inducers or inhibitors; drugs that cannot be coadministered with rapamycin include but are not limited to: calcium channel blockers: nicardipine, antifungal agents: clotrimazole, fluconazole, antibiotics: troleandomycin, gastrointestinal prokinetic agents: cisapride, metoclopramide; other drugs: bromocriptine, cimetidine, danazol, human immunodeficiency virus (HIV)-protease inhibitors (e.g., ritonavir, indinavir), anticonvulsants: carbamazepine, phenobarbital, phenytoin, antibiotics: rifapentine
Current use of: Finasteroid (propecia), Efavirenz, Red Clover, Ketoconazole, CYP3A4 Inhibitors
Exposure to strong inhibitors or inducers of CYP3A4/5, P-glycoprotein (Pgp) (MDR1) and BCRP if taken within the stated washout periods before the first dose of study treatment; treatment with moderate inhibitors or inducers of CYP3A4/5, Pgp (MDR1) and BCRP should be used only if necessary and when alternatives are unavailable; cases should be discussed with the principal investigator
Use of concomitant medications that are known to be strong inhibitors or inducers of CYP3A4 enzyme unless participant can discontinue or switch medications.
Treatment with strong cytochrome P3A (CYP3A) inducers within 14 days before the first dose of pevonedistat. Participants must have no history of amiodarone use within 6 months before the first dose of pevonedistat nor require the use of these medications during the study.
Use of strong cytochrome P3A (CYP3A) inhibitors and CYP3A inducers or inhibitors or modulators of P-glycoprotein (P-gp) or breast cancer resistance protein (BCRP) within 1 week before the first dose of study drug.