Phase 1b Trial of Dinaciclib With Pembrolizumab for Advanced Breast Cancer
- Conditions
- Triple Negative Breast CancerAdvanced or Metastatic Breast Cancer
- Interventions
- Registration Number
- NCT01676753
- Lead Sponsor
- Jo Chien
- Brief Summary
The purpose of this trial is to determine the safety and tolerability (maximum tolerated dose (MTD)) of weekly dinaciclib in combination with pembrolizumab in patients with advanced breast cancer. Once this is defined, dose expansion will be performed at this MTD in patients with metastatic or locally advanced and unresectable triple negative breast cancer, to evaluate the efficacy of combined dinaciclib and pembrolizumab.
- Detailed Description
PRIMARY OBJECTIVE:
I. Define the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of dinaciclib
SECONDARY OBJECTIVE:
I. Evaluation of the preliminary efficacy of this combination using RECIST 1.1 and irRECIST.
EXPLORATORY OBJECTIVE:
I. Characterizing and correlating PDL-1 and MYC overexpression with clinical response.
OUTLINE:
This is an open-label phase Ib trial of weekly dinaciclib in combination pembrolizumab in participants with advanced triple negative breast cancer. Participants will undergo a single needle biopsy of a site of active disease prior to initiating treatment of Pembrolizumab and dinaciclib in 21 day cycles. The dose of dinaciclib will be escalated following a toxicity probability interval (TPI) design where dose-limiting toxicities (DLT) observed during the first cycle will be used to determine whether additional participants should be enrolled at the same, higher, or lower dose level. Treatment will continue until disease progression, intolerable toxicity, or participant withdraws consent. In the event of a complete response (CR), participants may elect to hold dinaciclib treatment and continue with pembrolizumab alone. At the time of radiographic disease progression, dinaciclib can be resumed at the same dose as at the time of discontinuation. Participants will be followed for 30 days after the last dose of treatment.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 32
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment (Dinaciclib, Pembrolizumab) Dinaciclib Pembrolizumab will be administered on Day 1, every 3 weeks at a fixed dose of 200 mg IV. Dinaciclib will be administered D1 and D8 of a 21 day cycle by 2-hour intravenous infusion starting at Dose Level (DL) 1 of 12 mg/m\^2. Further dose escalation cohorts are defined as follows: DL 2: 18 mg/m\^2, DL 3: 25 mg/m\^2, DL 4: 33 mg/m\^2, and DL 5: 50 mg/m\^2 Treatment (Dinaciclib, Pembrolizumab) Pembrolizumab Pembrolizumab will be administered on Day 1, every 3 weeks at a fixed dose of 200 mg IV. Dinaciclib will be administered D1 and D8 of a 21 day cycle by 2-hour intravenous infusion starting at Dose Level (DL) 1 of 12 mg/m\^2. Further dose escalation cohorts are defined as follows: DL 2: 18 mg/m\^2, DL 3: 25 mg/m\^2, DL 4: 33 mg/m\^2, and DL 5: 50 mg/m\^2
- Primary Outcome Measures
Name Time Method Proportion of participants with reported dose-limiting toxicities (DLTs) Up to 1 cycle (1 cycle is equal to 21 days) Dose-limiting hematologic and non-hematologic toxicities classified using the CTCAE, will be based on events occurring during the first cycle of study drug administration. To be considered a dose-limiting toxicity, an adverse experience must be related to one or both of the study drugs, and must not be related to disease progression or intercurrent illnesses. Participants must receive Day 1 and Day 8 treatments of dinaciclib during the first cycle in order to be evaluable for DLTs (unless missed doses are due to toxicity).
Maximum tolerated dose (MTD) Up to 1 cycle (1 cycle is equal to 21 days) The MTD is determined by the number of dose-limiting toxicities reported by participants in the first cycle of treatment.
- Secondary Outcome Measures
Name Time Method Overall Response Rate Up to 3 years Overall tumor response and time to progression will be assessed using RECIST (Response Evaluation Criteria in Solid Tumors) 1.1 criteria and immune-related RECIST (irRECIST) which takes into account the clinical condition/stability of subjects in addition to tumor imaging. The rate of participants with a confirmed response classified as Complete Response (CR, iCR) (the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm) or a Partial Response (PR, iPR) (defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters or unconfirmed progressive disease (iUPD) will be reported.
Trial Locations
- Locations (1)
University of California, San Francisco
🇺🇸San Francisco, California, United States
University of California, San Francisco🇺🇸San Francisco, California, United States