Overview

This trial is active, not recruiting.

Condition solid tumors
Treatments mln4924 and docetaxel, mln4924 + paclitaxel + carboplatin (arm 2), mln4924 + gemcitabine (arm 3)
Phase phase 1
Sponsor Millennium Pharmaceuticals, Inc.
Start date July 2013
End date February 2016
Trial size 72 participants
Trial identifier NCT01862328, C15010

Summary

This is an open-label, multicenter, phase 1b, dose escalation study of MLN4924 plus docetaxel, gemcitabine or combination of carboplatin and paclitaxel in adult patients with solid tumors.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
mln4924 and docetaxel
MLN4924 (IV) and Docetaxel (IV) in patients to determine maximum tolerated dose (MTD) on a 21-day cycle: MLN4924 on Days 1,3,5 of each cycle Docetaxel on Day 1 of each cycle On Day 1 of each cycle, patients receive both agents
(Experimental)
mln4924 + paclitaxel + carboplatin (arm 2)
MLN4924 (IV) Paclitaxel (IV), and Carboplatin (IV) in patients to determine maximum tolerated dose (MTD) on a 21-day cycle: MLN4924 on Days 1,3,5 of each cycle Paclitaxel on Day 1 of each cycle Carboplatin on Day 1 of each cycle On Day 1 of each cycle, patients receive all 3 agents
(Experimental)
mln4924 + gemcitabine (arm 3)
MLN4924 (IV) and Gemcitabine (IV) in patients to determine maximum tolerated dose (MTD) on a 28-day cycle: •MLN4924 and Gemcitabine on Days 1,8,15 of each cycle

Primary Outcomes

Measure
Number of Adverse events
time frame: Recorded from the first dose of any study drug through 30 days (+ 10 days) after the last dose of study drug

Secondary Outcomes

Measure
MLN4924 plasma concentration time data for population PK analysis
time frame: Depending on study arm and whether the patient is in dose escalation/MTD expansion, the maximum sampling schedule is days 1, 2, 3, 5, and 6 of first cycle
Disease response rate
time frame: Scans will occur at screening and approximately every 2 months once the patient is on study medication for up to 1 year on study medication

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Male or female patients 18 years of age or older - ECOG PS 0 or 1 - Patients must 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 - Recovered from the effects of prior antineoplastic therapy - Female patients who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or agree to practice true abstinence - Male patients who agree to practice effective barrier contraception or agree to practice true abstinence - Voluntary written consent must be given before performance of any study-related procedure - Suitable venous access for the study-required blood sampling - Adequate clinical laboratory values during the screening period as specified in the protocol - Patients who are willing to refrain from donating blood for at least 90 days after their final dose of MLN4924 and (for male patients) willing to refrain from donating semen for at least 4 months after their final dose of MLN4924 - 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: - Major surgery within 14 days before the first dose of study drug - Female patients who are lactating or pregnant - Active uncontrolled infection or severe infectious disease - Receiving antibiotic therapy within 14 days before the first dose of study treatment - Life-threatening illness unrelated to cancer - Known hypersensitivity to study-assigned chemotherapy - Prior treatment with MLN4924; however, prior treatment with docetaxel, paclitaxel,carboplatin, and gemcitabine is allowed - History of severe hypersensitivity reactions to docetaxel (polysorbate 80-based formulations) for patients to be enrolled in Arm 1 (MLN4924 + docetaxel), history of hypersensitivity to carboplatin for patients to be enrolled in Arm 2 (MLN4924 + paclitaxel + carboplatin), or history of severe hypersensitivity to paclitaxel (cremophor-based formulations) for patients to be enrolled in Arm 2 - Persistent diarrhea (greater than Grade 2) lasting > 3 days within 2 weeks before the first dose of study treatment - Systemic antineoplastic therapy within 21 days before the first dose of study drug - Radiotherapy within 14 days preceding the first dose of study treatment - Prior treatment with radiation therapy involving ≥ 25% of the hematopoietically active bone marrow - 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 - Clinically uncontrolled central nervous system (CNS) involvement - Any serious medical or psychiatric illness - Treatment with any investigational products 21 days prior to treatment - Patients currently taking statins who are unwilling or unable to refrain from using statins 24 hours before, the day of, and 24 hours after each MLN4924 administration - Known human immunodeficiency virus (HIV) positive or hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection - Known hepatic cirrhosis - Known cardiac/cardiopulmonary disease - Left ventricular ejection fraction - Patients with a cardiac pacer whose heart rate is set at a fixed rate and patients on concomitant medication that may limit increase in heart rate in response to hypotension - History of severe intolerance to cytotoxic agent(s) given in the assigned arm

Additional Information

Official title A Phase 1b, Open-Label, Dose Escalation, Multi-arm Study of MLN4924 Plus Docetaxel, Gemcitabine, or Combination of Carboplatin and Paclitaxel in Patients With Solid Tumors
Trial information was received from ClinicalTrials.gov and was last updated in October 2016.
Information provided to ClinicalTrials.gov by Takeda.