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Phase 1 N=64 Other

Dose Escalation, Multi-arm Study of MLN4924 Plus Docetaxel, Gemcitabine, or Combination of Carboplatin and Paclitaxel in Participants With Solid Tumors

Solid Tumors

Enrolled (actual)
64
Serious AEs
40.6%
Results posted
Jun 2020
Primary outcome: Primary: Number of Participants Who Experience at Least 1 Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) — 4; 18; 6; 7 Participants

Study Design & Population

Study type
Interventional
Phase
Phase 1
Interventions
MLN4924 (Drug); Paclitaxel (Drug); Gemcitabine (Drug); Docetaxel (Drug); Carboplatin (Drug)
Age
Adult, Older Adult · 18+ yrs
Sex
All
Sponsor
Millennium Pharmaceuticals, Inc.
Primary completion
May 2018

Outcome Measures

OutcomeResultp-value
PRIMARY
Number of Participants Who Experience at Least 1 Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
4; 18; 6; 7; 12; 7
PRIMARY
Number of Participants With TEAEs Related to Clinically Significant Laboratory Evaluation Findings
1; 4; 2; 2; 7; 2
PRIMARY
Number of Participants With TEAEs Related to Clinically Significant Vital Sign Findings
0; 2; 1; 0; 0; 0
SECONDARY
Percentage of Participants With Objective Response
0; 0; 0; 0; 18; 0
SECONDARY
Duration of Response
2.880; 2.270; 16.153; 7.015
SECONDARY
Dose-escalation Phase: Plasma Concentrations-time Data of MLN4924
163.8; 197.1; 275.7; 257.3; 372.7; 222.0
SECONDARY
MTD Expansion Phase: Plasma Concentrations-time Data of MLN4924
152.8; 429.8; 137.3; 253.6; 86.4; 192.8

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

  • 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, 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 greater than or equal to (>=) 25% of the hematopoietically active bone marrow
  • 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

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01862328). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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