Effects of Fluconazole and Itraconazole CYP3A-Mediated Inhibition on the Pharmacokinetics, Safety, and Tolerability of MLN4924 in Participants With Advanced Solid Tumors

1. Prior treatment with MLN4924; however, prior treatment with docetaxel, paclitaxel, and carboplatin is allowed.

2. Treatment with any systemic antineoplastic therapy or investigational products within 21 days before the first dose of study treatment.

3. Radiotherapy within 14 days before the first dose of study treatment.

4. Prior treatment with radiation therapy involving \>= 25 percent (%) of hematopoietically active bone marrow.

5. Known hypersensitivity or history of severe intolerance or toxicity to study-assigned chemotherapy. Note: History of severe hypersensitivity reactions to docetaxel (polysorbate 80-based formulations) for participants to be treated with MLN4924 + docetaxel; history of hypersensitivity to carboplatin for participants to be treated with MLN4924 + carboplatin + paclitaxel; or history of severe hypersensitivity to paclitaxel (Cremophor-based formulations) for participants to be treated with MLN4924 + carboplatin + paclitaxel in Part B.

6. Known hypersensitivity/allergy to fluconazole or itraconazole or their respective excipients.

7. Systemic treatment with moderate and strong cytochrome P450 (CYP) CYP3A inhibitors or inducers must be discontinued at least 14 days before the first dose of MLN4924. Moderate and strong CYP3A inhibitors and CYP3A inducers are not permitted during the study. Participants must have no history of amiodarone use in the 6 months before the first dose of MLN4924.

8. Any life-threatening or serious medical or psychiatric illness unrelated to cancer that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.

9. Major surgery within 14 days before the first dose of study treatment.

10. Active uncontrolled infection or severe infectious disease, such as pneumonia, meningitis, septicemia, or methicillin-resistant Staphylococcus aureus infection.

11. Clinically significant central nervous system disease defined as untreated, progressive, or requiring steroids for control of symptoms.

12. Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of fluconazole or itraconazole including difficulty swallowing capsules.

13. Persistent diarrhea (\>= Grade 2) lasting greater than (\>) 3 days within 2 weeks before the first dose of study treatment.

14. Known hepatic cirrhosis, hepatitis B surface antigen-positive status, or suspected active hepatitis C infection. Note: Participants who have isolated positive hepatitis B core antibody (that is, in the setting of negative hepatitis B surface antigen and negative hepatitis B surface antibody) must have an undetectable hepatitis B viral load.

15. Known human immunodeficiency virus (HIV) positive status.

16. Female participants who are lactating and breastfeeding or have a positive serum pregnancy test during the Screening period or a positive urine pregnancy test on Day 1 before first dose of study drug.

17. Uncontrolled high blood pressure (that is, systolic blood pressure \>180 millimeter of mercury \[mmHg\], diastolic blood pressure \>95 mmHg).

18. Left ventricular ejection fraction \< 50% as assessed by echocardiogram or radionuclide angiography.

19. Congestive heart failure New York Heart Association Class III or IV, or Class II with a recent decompensation requiring hospitalization within 4 weeks before screening.

20. Cardiomyopathy or history of ischemic heart disease.

o Participants with ischemic heart disease who have had acute coronary syndrome (ACS), myocardial infarction (MI), or revascularization (example, coronary artery bypass graft, stent) in the past 6 months are excluded. However, participants with ischemic heart disease who have had ACS, MI, or revascularization greater than 6 months before screening and who are without cardiac symptoms may enroll.

21. Arrhythmia (example, history of polymorphic ventricular fibrillation or torsade de pointes). However, participants with \< Grade 3 atrial fibrillation for a period of at least 6 months may enroll. Grade 3 atrial fibrillation is defined as symptomatic and incompletely controlled medically, or controlled with device (example, pacemaker) or ablation, and is excluded. Participants with paroxysmal atrial fibrillation are permitted to enroll.

22. Prolonged rate corrected QT interval (QTc) \>=500 millisecond (msec), calculated according to institutional guidelines.

23. Implantable cardioverter defibrillator.

24. Participants with a cardiac pacer whose heart rate is set at a fixed rate and participants on concomitant medication that may limit increase in heart rate in response to hypotension (example, high-dose beta blocker).

25. Moderate to severe aortic or mitral stenosis or other valvulopathy (ongoing).

26. Known moderate to severe chronic obstructive pulmonary disease (COPD), interstitial lung disease, pulmonary fibrosis, and pulmonary arterial hypotension.

Effects of Fluconazole and Itraconazole CYP3A-Mediated Inhibition on the Pharmacokinetics, Safety, and Tolerability of MLN4924 in Participants With Advanced Solid Tumors

What this study is about

Effects of Fluconazole and Itraconazole CYP3A-Mediated Inhibition on the Pharmacokinetics, Safety, and Tolerability of MLN4924 in Participants With Advanced Solid Tumors

What this study is about