Any patient requiring cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) isoform-inducing drugs (e.g. phenytoin, phenobarbital, carbamazepine, rifampin, rifabutin, ketoconazole, St. Johns wort) will be excluded; CYP3A4-inducing drugs should be discontinued at least 2 weeks prior to the first cycle of irinotecan
Concurrent treatment with any medications or substances that are potent inhibitors or inducers of cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4), hepatic enzyme inducing antiepileptic drugs (EIAEDs), or other drugs known to affect the metabolism of modafinil; examples include, but are not limited to, itraconazole, ketoconazole, doxycycline, rifampin, St. John's wort, phenytoin, phenobarbital, diazepam, and tricyclic antidepressants* If patients were previously taking EIAEDs, they must be off for > 2 weeks prior to study enrollment
Receiving any medications or substances that are inducers of CYP3A4; use of the following inducers are prohibited =< 7 days prior to registration* Inducers of CYP3A4 ** Efavirenz (Sustiva)** Nevirapine (Viramune)** Carbamazepine (Carbatro, Epitol, Equetro, Tegretol, Tegretol-XR)** Modafinil (Provigil)** Phenobarbital (Luminal)** Phenytoin (Dilantin, Phenytek)** Pioglitazone (Acto)** Rifabutin (Mycobutin)** Rifampin (Rifadin)** St. Johns wort
Strong inhibitors and inducers of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) should be avoided whenever possible or switched to alternatives; subjects requiring chronic concomitant treatment of strong CYP3A4 inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, and St. Johns wort) are not eligible for this study
The participant requires chronic concomitant treatment with the following strong cytochrome P450 family 3, subfamily A, polypeptide 4 (CYP3A4) inducers OTHER than antiretroviral agents: dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, primidone, modafinil, and other enzyme inducing anti-convulsant drugs (EIACD), and St. Johns wort; use of efavirenz or etravirine is permitted for participants considered for the CYP3A4-inducer based antiretroviral therapy (ART) regimen arm (Stratum B) of the trial; 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
Patients may not be on drugs known to be moderate or potent inhibitors/inducers of CYP3A4, sensitive substrates of CYP3A4, or substrates of CYP3A4 with narrow therapeutic windows
The subject requires chronic concomitant treatment of strong CYP3A4 inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, and St. Johns wort)
Inability to swallow oral medication or to maintain a fast as required for 2 hours before and 1 hour after MLN8237 administration or any condition that would modify small bowel absorption of oral medications, including malabsorption, or resection of pancreas or upper bowel; treatment with clinically significant enzyme inducers, such as the enzyme-inducing antiepileptic drugs phenytoin, carbamazepine, oxcarbazepine, primidone or phenobarbital, or rifampin, rifabutin, rifapentine, or St. John's wort within 14 days prior to the first dose of MLN8237 and during the study; patients must be cautiously co-medicated with agents that cause corrected QT interval (QTc) prolongation and agents that are strong or moderate enzyme inhibitors during the study
Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A or CYP2C8 are ineligible; current use of, or intended ongoing treatment with: herbal remedies (e.g., St. Johns wort), or strong inhibitors or inducers of permeability-glycoprotein (Pgp) or breast cancer resistance protein 1 (Bcrp1) should also be excluded; below are a few examples of the agents:* Strong inducers of CYP3A or CYP2C8:** Antibiotics: rifamycin class agents (e.g., rifampin, rifabutin, rifapentine)** Anticonvulsants: carbamazepine, oxcarbazepine, phenobarbital, phenytoin, s-mephenytoin** Miscellaneous: bosentan, St. John's wort* Strong inhibitors of CYP3A or CYP2C8** Antibiotics: clarithromycin, telithromycin, troleandomycin** Antidepressants: nefazodone** Antifungals: itraconazole, ketoconazole, posaconazole, voriconazole** Hyperlipidemia: gemfibrozil** Antiretroviral: ritonavir, saquinavir, atazanavir** Miscellaneous: conivaptan
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
CYP3A4 inducers: patients 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, ritonavir, and St. Johns wort are not eligible; the topical use of these medications (if applicable) is allowed
Concurrent use of strong CYP3A4/5 inducers such as carbamazepine, phenytoin, rifampin, and St. Johns wort are prohibited
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 Inducers: patients chronically receiving drugs that are known potent CYP3A4 inducers within 14 days prior to study enrollment, including but not limited to carbamazepine, phenobarbital, phenytoin, rifampin, and St. Johns wort are not eligible (with the exception of glucocorticoids)
The subject requires chronic concomitant treatment of strong cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, and St. Johns wort)
Patients cannot be on systemic treatment with strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital) or use Ginkgo biloba or St. Johns wort within 14 days of registration
Patients currently receiving (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be potent inducers of CYP3A4 (at least 3 weeks prior); all patients must try to avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known inducer effects of CYP3A4
Patients must be willing to not take St. John wort or grapefruit juice while participating in this trial and should avoid drugs that are strong inducers of P-gp, and to switch to alternative drugs when available
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
Strong CYP3A4 inhibitors and inducers; concomitant use of strong inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir, indinavir, nelfinavir and saquinavir), and inducers of CYP3A4 (e.g., rifampin, phenytoin, carbamazepine, phenobarbital, St. John's Wort) are not permitted within two weeks prior to start of study treatment and for the duration of treatment with copanlisib
Patients must not be receiving any of the following potent CYP3A4 inducers or inhibitors: erythromycin, clarithromycin, ketoconazole, azithromycin, itraconazole, grapefruit juice or St. Johns wort
Concomitant use of known strong CYP3A inhibitors (eg. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir), moderate CYP3A inhibitors (eg. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil), strong CYP3A inducers (eg. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St Johns wort) or moderate CYP3A inducers (eg. bosentan, efavirenz, modafinil); a minimum washout period of 2 weeks prior to cycle 1 day 1 is required for strong inhibitors, and at least one week for moderate inhibitors; a minimum washout period of 4 weeks prior to cycle 1 day 1 is required for CYP3A inducers; a minimum washout period of 5 weeks prior to cycle 1 day 1 is required for enzalutamide or phenobarbital; dihydropyridine calcium-channel blockers are permitted for management of hypertension
Patients requiring concomitant therapy with phenytoin, phenobarbital, carbamazepine, or valproic acid
Patients currently receiving (or unable to stop use prior to receiving the first dose of study treatment) medications or herbal supplements known to be potent inducers of CYP3A4 (at least 3 week prior); all patients must try to avoid concomitant use of any medications, herbal supplements and/or ingestion of foods with known inducer effects on CYP3A4