Dose Escalation, Multi-arm Study of MLN4924 Plus Docetaxel, Gemcitabine, or Combination of Carboplatin and Paclitaxel in Participants With Solid Tumors
Condition: Solid Tumors
MeSH terms: Neoplasms
Intervention: MLN4924; Paclitaxel; Gemcitabine; Docetaxel; Carboplatin
Intervention description: MLN4924 (intravenously [IV]) in participants in a 21-day cycle:
MLN4924 on Days 1,3,5 of each cycle; Paclitaxel (IV) in a 21-day cycle:
Paclitaxel on Day 1 of each cycle; Gemcitabine (IV) in participants in a 28-day cycle:
-Gemcitabine on Days 1,8,15 of each cycle; Docetaxel (IV) in participants in a 21-day cycle:
- Docetaxel on Day 1 of each cycle; Carboplatin (IV) in participants in a 21-day cycle:
- Carboplatin on Day 1 of each cycle
Intervention MeSH terms: Paclitaxel; Docetaxel; Carboplatin; Gemcitabine; Pevonedistat
Phase: Phase 1
Study type: Interventional
Primary purpose: Other
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 64.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: MLN4924; Solid Tumors

Summary:

      The purpose of this study is to establish the maximum tolerated dose (MTD) and assess the
      safety and tolerability of MLN4924 (pevonedistat) in combination with docetaxel, paclitaxel
      and carboplatin, and gemcitabine in participants with solid tumors.
    

Eligibility criteria:

        Inclusion Criteria:

          1. 18 years of age or older

          2. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1

          3. Have a histologically or cytologically confirmed metastatic or locally advanced and
             incurable solid tumor that is felt to be appropriate for treatment with 1 of the 3
             chemotherapy regimens in this study, or have progressed despite standard therapy, or
             for whom conventional therapy is not considered effective. The tumor must be
             radiographically or clinically evaluable and/or measurable

          4. Recovered (that is, <=Grade 1 toxicity) from the effects of prior antineoplastic
             therapy

          5. Female participants who are post menopausal, surgically sterile, or agree to practice
             2 effective methods of contraception or agree to practice true abstinence

          6. Male participants who agree to practice effective barrier contraception or agree to
             practice true abstinence

          7. Voluntary written consent must be given before performance of any study-related
             procedure

          8. Suitable venous access for the study-required blood sampling

          9. Adequate clinical laboratory values during the screening period as specified in the
             protocol

         10. Participants who are willing to refrain from donating blood for at least 90 days after
             their final dose of MLN4924 and (for male participants) willing to refrain from
             donating semen for at least 4 months after their final dose of MLN4924

         11. Availability of fixed tumor specimen (block or slides) for exploratory biomarker
             analysis. If no slides or block are available, fresh tumor biopsies should be obtained
             and used for these assessments

        Exclusion Criteria:

          1. Major surgery within 14 days before the first dose of study drug

          2. Female participants who are lactating or pregnant

          3. Active uncontrolled infection or severe infectious disease

          4. Receiving antibiotic therapy within 14 days before the first dose of study treatment

          5. Life-threatening illness unrelated to cancer

          6. Known hypersensitivity to study-assigned chemotherapy

          7. Prior treatment with MLN4924; however, prior treatment with docetaxel,
             paclitaxel,carboplatin, and gemcitabine is allowed

          8. History of severe hypersensitivity reactions to docetaxel (polysorbate 80-based
             formulations) for participants to be enrolled in Arm 1 (MLN4924 + docetaxel), history
             of hypersensitivity to carboplatin for participants to be enrolled in Arm 2 (MLN4924 +
             paclitaxel + carboplatin), or history of severe hypersensitivity to paclitaxel
             (cremophor-based formulations) for participants to be enrolled in Arm 2

          9. Persistent diarrhea (greater than Grade 2) lasting >3 days within 2 weeks before the
             first dose of study treatment

         10. Systemic antineoplastic therapy within 21 days before the first dose of study drug

         11. Radiotherapy within 14 days preceding the first dose of study treatment

         12. Prior treatment with radiation therapy involving greater than or equal to (>=) 25% of
             the hematopoietically active bone marrow

         13. Treatment with cytochrome P450 3A (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. Participants
        must have no history of amiodarone use in the 6 months before the first dose of MLN4924 14.
        Clinically uncontrolled central nervous system (CNS) involvement 15. Any serious medical or
        psychiatric illness 16. Treatment with any investigational products 21 days prior to
        treatment 17. Unwilling or unable to refrain from using statins 24 hours before, the day
        of, and 24 hours after each MLN4924 administration 18. Known human immunodeficiency virus
        (HIV) positive or hepatitis B surface antigen-positive status, or known or suspected active
        hepatitis C infection 19. Known hepatic cirrhosis 20. Known cardiac/cardiopulmonary disease
        21. Left ventricular ejection fraction 23. 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 24 History of severe intolerance to cytotoxic agent(s)
        given in the assigned arm