Clinical Trials/NCT01862328

NCT01862328

Completed

Phase 1

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

Millennium Pharmaceuticals, Inc.0 sites64 target enrollmentJune 10, 2013

ConditionsSolid Tumors

InterventionsCarboplatin MLN4924 Docetaxel Paclitaxel Gemcitabine

DrugsMLN4924 Paclitaxel Gemcitabine Docetaxel Carboplatin

Overview

Phase: Phase 1
Intervention: Carboplatin
Conditions: Solid Tumors
Sponsor: Millennium Pharmaceuticals, Inc.
Enrollment: 64
Primary Endpoint: Number of Participants Who Experience at Least 1 Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Status: Completed
Last Updated: 5 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Similar Trials

Overview

Brief 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.

Registry

clinicaltrials.gov

Start Date

June 10, 2013

End Date

May 21, 2018

Last Updated

5 years ago

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

Millennium Pharmaceuticals, Inc.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•18 years of age or older
•Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
•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 (that is, \<=Grade 1 toxicity) from the effects of prior antineoplastic therapy
•Female participants who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or agree to practice true abstinence
•Male participants 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
•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

Exclusion Criteria

•Major surgery within 14 days before the first dose of study drug
•Female participants 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 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
•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

Arms & Interventions

MLN4924 + Paclitaxel + Carboplatin (Arm 2)

Intervention: Carboplatin

MLN4924 and Docetaxel (Arm 1)

Intervention: MLN4924

MLN4924 and Docetaxel (Arm 1)

Intervention: Docetaxel

MLN4924 + Paclitaxel + Carboplatin (Arm 2)

Intervention: MLN4924

MLN4924 + Paclitaxel + Carboplatin (Arm 2)

Intervention: Paclitaxel

MLN4924 + Gemcitabine (Arm 3)

Intervention: MLN4924

MLN4924 + Gemcitabine (Arm 3)

Intervention: Gemcitabine

Outcomes

Primary Outcomes

Number of Participants Who Experience at Least 1 Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

Time Frame: Baseline up to 30 days after the last dose of study drug (up to 5 years)

Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings

Time Frame: Baseline up to 30 days after the last dose of study drug (up to 5 years)

Number of Participants With TEAEs Related to Clinically Significant Vital Sign Findings

Time Frame: Baseline up to 30 days after the last dose of study drug (up to 5 years)

Secondary Outcomes

Dose-escalation Phase: Plasma Concentrations-time Data of MLN4924(Cycle 1 Day 1 pre-dose and at multiple time points (up to 20 hours) post-dose (Cycle Length=21 days [Arm 1 and 2] and 28 days [Arm 3]))
MTD Expansion Phase: Plasma Concentrations-time Data of MLN4924(Cycle 1 Days 1 and 5 pre-dose and at multiple time points (up to 20 hours) post-dose (Cycle Length=21 days [Arm 1 and 2]))
Percentage of Participants With Objective Response(Screening, Cycle 2 Days 15 (Arm 1, 2a, and 2) and 22 (Arm 3) then every other Cycle thereafter up to 30 days after the last dose of study drug (up to 5 years) (Cycle Length = 21 days [Arm 1, 2a, and 2] and 28 days [Arm 3]))
Duration of Response(From the date of first documented response (CR or PR) to the date of first documented PD or the date of last disease assessment if the participants discontinued the study before PD (up to 5 years))