CYP3A4 Inhibitors: patients chronically receiving drugs that are known potent CYP3A4 inhibitors within 7 days prior to study enrollment, including but not limited to itraconazole, clarithromycin, erythromycin many non-nucleoside reverse-transcriptase inhibitors (NNRTIs), diltiazem, verapamil, and grapefruit juice are not eligible
CYP3A4 inhibitors: patients chronically receiving drugs that are known potent CYP3A4 inhibitors within 7 days prior to study enrollment, including but not limited to ketoconazole, itraconazole, clarithromycin, erythromycin, ritonavir, indinavir, nelfinavir, saquinavir, delavirdine, nefazodone, diltiazem, verapamil, and grapefruit juice are not eligible; the topical use of these medications (if applicable), e.g. 2% ketoconazole cream, is allowed
PIK3CA MUTANT AND WILD TYPE COHORT (closed 03/17/2016): Current use or anticipated need for food or drugs that are known strong cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors (i.e. grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, posaconazole, erythromycin, clarithromycin, telithromycin, indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, atazanavir, amprenavir, fosamprenavir, nefazodone, diltiazem, and delavirdine) or inducers (i.e. dexamethasone, glucocorticoids, progesterone, rifampin, phenobarbital, St. John’s wort)
Anti-HIV agents: delavirdine, nelfinavir, amprenavir, ritonavir, indinavir, saquinavir, lopinavir
Current use or anticipated need for treatment with drugs or foods that are known strong CYP3A4/5 inhibitors, including their administration within 10 days prior to patient treatment with study drug (eg, grapefruit juice or grapefruit/grapefruit-related citrus fruits [eg, Seville oranges, pomelos], ketoconazole, miconazole, itraconazole, voriconazole, posaconazole, clarithromycin, erythromycin, telithromycin, indinavir, saquinavir, ritonavir, nelfinavir, amprenavir, fosamprenavir nefazodone, lopinavir, troleandomycin, mibefradil, and conivaptan); the topical use of these medications (if applicable), such as 2% ketoconazole cream, is allowed
Treated within the last 7 days prior to day 1 of protocol therapy with:\r\n* Food or drugs that are known to be CYP3A4 inhibitors (e.g. grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, erythromycin, clarithromycin, telithromycin, indinavir, ritonavir, nelfinavir, atazanavir, amprenavir, nefazodone, diltiazem, and delavirdine) or inducers (e.g. glucocorticoids, progesterone, rifampin, phenobarbital, St. John’s wort)\r\n* Drugs that are known to prolong the QT interval\r\n* Drugs that are proton pump inhibitors
Current use or anticipated need for food or drugs that are known strong or moderate CYP3A4 inhibitors, including their administration within 2 weeks prior to the first study treatment (ie, strong CYP3A4 inhibitors: grapefruit juice or grapefruit/grapefruit related citrus fruits [eg, Seville oranges, pomelos], ketoconazole, miconazole, itraconazole, voriconazole, posaconazole, clarithromycin, telithromycin, indinavir, saquinavir, ritonavir, nelfinavir, amprenavir, fosamprenavir nefazodone, lopinavir, troleandomycin, mibefradil, and conivaptan; moderate CYP3A4 inhibitors: erythromycin, verapamil, atazanavir, delavirdine, fluconazole, darunavir, diltiazem, aprepitant, imatinib, tofisopam, ciprofloxacin, cimetidine); for participants in the dose escalation portion, no CYP3A4 inhibitors should be administered during the first 21 days of the study, regardless of strength
Current or anticipated use of the following P gp inhibitors (amiodarone, carvedilol, clarithromycin, cobicistat, darunavir, dronedarone, erythromycin, indinavir, itraconazole, ketoconazole, lapatinib, lopinavir, propafenone, quinidine, ranolazine, ritonavir, saquinavir, telaprevir, tipranavir, verapamil, and valspodar), P gp inducers (avasimibe, carbamazepine, phenytoin, rifampin, and St. John's wort), or BCRP inhibitors (curcumin, cyclosporine, elacridar [GF120918] and eltrombopag).
Concomitant use of a strong CYP3A inhibitors (e.g., itraconazole, telithromycin, clarithromycin, ketoconazole, voriconazole, nefazodone, posaconazole, ritonavir, lopinavir/ritonavir, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) and moderate CYP3A inhibitors (e.g., amprenavir, aprepitant, atazanavir, ciprofloxacin, crizotinib, darunavir/ritonavir, diltiazem, erythromycin, fluconazole. Fosamprenavir, imatinib, verapamil)
Current use or anticipated need for food or drugs that are known strong CYP3A4 inhibitors (i.e., grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, posaconazole, erythromycin, clarithromycin, telithromycin, indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, atazanavir, amprenavir, fosamprenavir, nefazodone, diltiazem, and delavirdine) or inducers (i.e. dexamethasone, glucocorticoids, progesterone, rifampin, phenobarbital, St. John’s wort)
Concomitant medications \r\n* Corticosteroids: subjects receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for at least 7 days prior to enrollment are not eligible\r\n* Investigational drugs: subjects who are currently receiving another investigational drug are not eligible\r\n* Anti-cancer agents: subjects who are currently receiving other anti-cancer agents are not eligible\r\n* Anti-graft-versus-host disease (GVHD) agents post-transplant: subjects who are receiving cyclosporine, tacrolimus, or other agents to prevent graft-versus-host disease post bone marrow transplant are not eligible for this trial\r\n* Study specific: subjects who are unable to swallow a tablet or swallow liquid are still eligible provided they have a nasogastric (NG) or gastric (G) tube through which the medicine can be administered\r\n* Cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors: subjects chronically receiving drugs that are known potent CYP3A4 inhibitors within 7 days prior to study enrollment, including but not limited to ketoconazole, itraconazole, miconazole, clarithromycin, erythromycin, ritonavir, indinavir, nelfinavir, saquinavir, amprenavir, delavirdine, nefazodone, diltiazem, verapamil, and grapefruit juice are not eligible; the topical use of these medications (if applicable), e.g. 2% ketoconazole cream, is allowed\r\n * CYP3A4 inducers: subjects chronically receiving drugs that are known potent CYP3A4 inducers within 12 days prior to study enrollment, including but not limited to carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, tipranavir, ritonavir, and St. John’s wort are not eligible
Anticipated need for treatment with drugs that are known potent CYP3A4 inhibitors (i.e., verapamil, ketoconazole, miconazole, itraconazole, erythromycin, telithromycin, clarithromycin, indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, atazanavir, amprenavir, fosamprenavir and delavirdine); grapefruit juice is also a CYP3A4 inhibitor
Drugs that potently inhibit or induce CYP3A4 should be administered with caution; below are a few examples of the agents:\r\n* Drugs that may increase exposure of trametinib (CYP3A4 inhibitors):\r\n** Antivirals: amprenavir, atazanavir, fosamprenavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir\r\n** Antibiotics: clarithromycin, erythromycin, telithromycin, troleandomycin\r\n** Antifungals: fluconazole, itraconazole, ketoconazole, voriconazole\r\n** Antidepressants: nefazodone\r\n** Calcium channel blockers: mibefradil, diltiazem, verapamil\r\n** Miscellaneous: aprepitant\r\n* Drugs that may decrease exposure of trametinib (CYP3A4 inducers)\r\n** Antivirals: efavirenz, nevirapine\r\n** Antibiotic: rifampin\r\n** Anticonvulsants: carbamazepine, phenobarbital, phenytoin\r\n* Caution should be exercised when dosing trametinib concurrently with medications with narrow therapeutic windows that are substrates of CYP2C8; below are a few examples of the agents\r\n** Drug metabolism potentially affected by trametinib resulting in increased exposure of these substrates\r\n*** 3-hydroxy-3-methyl-glutaryl-CoA (HMG CoA)-reductase inhibitors: cerivastatin\r\n*** Thiazolidinediones: rosiglitazone, pioglitazone\r\n*** Miscellaneous: chloroquine, zopiclone, repaglinide\r\n* As part of the enrollment/informed consent procedures, the patient 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 patient is considering a new over-the-counter medicine or herbal product
Patients chronically receiving drugs that are known potent CYP3A4 inhibitors within 7 days prior to study enrollment, including but not limited to ketoconazole, itraconazole, miconazole, clarithromycin, erythromycin, ritonavir, indinavir, nelfinavir, saquinavir, amprenavir, delavirdine, nefazodone, diltiazem, verapamil, and grapefruit juice are not eligible; the topical use of these medications (if applicable), e.g. 2% ketoconazole cream, is allowed
Patients chronically receiving drugs that are known potent CYP3A4 inhibitors within 7 days prior to study enrollment, including but not limited to, ketoconazole, itraconazole, miconazole, clarithromycin, erythromycin, ritonavir, indinavir, nelfinavir, saquinavir, amprenavir, delavirdine, nefazodone, diltiazem, verapamil, and grapefruit juice are not eligible; the topical use of these medications (if applicable), e.g. 2% ketoconazole cream, is allowed
Treated within the last 7 days prior to day 1 of protocol therapy with:\r\n* Food or drugs that are known to be CYP3A4 inhibitors (e.g. grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, erythromycin, clarithromycin, telithromycin, indinavir, ritonavir, nelfinavir, atazanavir, amprenavir, nefazodone, diltiazem, and delavirdine) or inducers (i.e. dexamethasone, glucocorticoids, progesterone, rifampin, phenobarbital, St. John’s wort)\r\n* Drugs that are known to prolong the QT interval\r\n* Drugs that are proton pump inhibitors
Use caution when co-administered with moderate CYP3A4/PgP inhibitors (e.g., amprenavir, fosamprenavir, aprepitant, erythromycin, fluconazole, verapamil, diltiazem).
Current use or anticipated need for treatment with drugs that are known potent CYP3A4 inhibitors (i.e., grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, erythromycin, telithromycin, clarithromycin, indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, atazanavir, amprenavir, fosamprenavir, and delavirdine)
Patients cannot receive cytochrome P450 3A (CYP3A4) inhibiting drugs including antibiotics (clarithromycin, erythromycin, troleandomycin), anti-HIV agents (delavirdine, nelfinavir, amprenavir, ritonavir, indinavir, saquinavir, lopinavir), antifungals (itraconazole, ketoconazole, fluconazole at doses > 200 mg/day, voriconazole), antidepressants (nefazodone, fluvoxamine), calcium channel blockers (verapamil, diltiazem) or amiodarone
Patients CANNOT be receiving enzyme-inducing or enzyme inhibiting agents listed here: Inhibitors: Amiodarone, Amprenavir, Atazanavir, Chloramphenicol, Clarithromycin, Conivaptan, Cyclosporine, Darunavir, Dasatinib, Delavirdine, Diltiazem, Erythromycin, Fluconazole, Fluoxetine, Fluvoxamine, Fosamprenavir, Imatinib, Indinavir, Isoniazid, Itraconazole, Ketoconazole, Lapatinib, Miconazole, Nefazodone, Nelfinavir, Posaconazole, Ritonavir, Quinupristin, Saquinavir, Tamoxifen, Telithromycin, Troleandomycin, Verapamil, Voriconazole; inducers: Aminoglutethimide, Bexarotene, Bosentan, Carbamazepine, Efavirenz, Fosphenytoin, Griseofulvin, Modafinil, Nafcillin, Nevirapine, Oxcarbazepine, Phenobarbital, Phenytoin, Primidone, Rifabutin, Rifampin, Rifapentine, St. John’s wort, Sulfadimidine, Sulfinpyrazone, Troglitazone, Troleandomycin; all concomitant medications must be recorded
Current use or anticipated need for food or drugs that are known strong cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors (i.e. grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, posaconazole, erythromycin, clarithromycin, telithromycin, indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, atazanavir, amprenavir, fosamprenavir, nefazodone, diltiazem, and delavirdine)
Current use or anticipated inability to avoid use of drugs that are known potent cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors (ie, grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, erythromycin, clarithromycin, ergot derivatives, indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, and delavirdine)
Treatment with strong cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors: \r\n* Cardiovascular: verapamil and diltiazem; \r\n* Antibiotics: clarithromycin, telithromycin, troleandomycin, erythromycin; \r\n* Human Immunodeficiency Virus (HIV): protease inhibitors (ritonavir, indinavir, saquinavir, nelfinavir, amprenavir, lopinavir); \r\n* Antifungals: itraconazole, ketoconazole, voriconazole, fluconazole; \r\n* Antidepressants: nefazodone
EXPANSION COHORT ONLY: Treatment with strong cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors: \r\n* Cardiovascular: verapamil and diltiazem; \r\n* Antibiotics: clarithromycin, telithromycin, troleandomycin, erythromycin; \r\n* Human Immunodeficiency Virus (HIV): protease inhibitors (ritonavir, indinavir, saquinavir, nelfinavir, amprenavir, lopinavir); \r\n* Antifungals: itraconazole, ketoconazole, voriconazole, fluconazole; \r\n* Antidepressants: nefazodone
Patients taking cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inhibitors such as ketoconazole, ritonavir, itraconazole, erythromycin, clarithromycin, nelfinavir, fluconazole, amiodarone, cyclosporine, diltiazem, nefazodone, fluvoxamine, verapamil, chloramphenicol, indinavir or saquinavir within 7 days of treatment
Patients receiving medications that may increase risk of rhabdomyolysis such as itraconazole, ketoconazole, erythromycin, cyclosporine, amiodarone, verapamil, clarithromycin, nefazodone, ranolazine, human immunodeficiency virus (HIV) protease inhibitors, gemfibrozil, posaconazole, danazol, amiodarone, diltiazem, and amlodipine
On scheduled strong or moderate CYP3A4 inhibitors (boceprevir, clarithromycin, conivaptan, indinavir, itraconazole, ketoconazole, lopinavir/ritonavir, mibefradil, nefazodone, posaconazole, ritonavir, saquinavir, telaprevir, telithromycin, voriconazole; amprenavir, aprepitant, atazanavir, ciprofloxacin, darunavir/ritonavir, diltiazem, erythromycin, fluconazole, fosamprenavir, grapefruit juice, imatinib, verapamil) within one week of study enrollment
Current use or anticipated need for food or drugs that are known strong or moderate CYP3A4 inhibitors, including their administration within 10 days prior to the first PF-06463922 dose (i.e., strong CYP3A4 inhibitors: grapefruit juice or grapefruit/grapefruit related citrus fruits [e.g., Seville oranges, pomelos], ketoconazole, miconazole, itraconazole, voriconazole, posaconazole, clarithromycin, telithromycin, indinavir, saquinavir, ritonavir, nelfinavir, amprenavir, fosamprenavir nefazodone, lopinavir, troleandomycin, mibefradil, and conivaptan; moderate CYP3A4 inhibitors: erythromycin, verapamil, atazanavir, delavirdine, fluconazole, darunavir, diltiazem, aprepitant, imatinib, tofisopam, ciprofloxacin, cimetidine)