Phase 1b Trial of Dinaciclib With Pembrolizumab for Advanced Breast Cancer

NCT01676753 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: 16758NCI-2018-01053
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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.

Conditions

Advanced or Metastatic Breast Cancer; Triple Negative Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose (MTD)

  The MTD is determined by the number of dose-limiting toxicities reported by participants in the first cycle of treatment.

  Up to 1 cycle (1 cycle is equal to 21 days)

• Proportion of participants with reported dose-limiting toxicities (DLTs)

  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).

  Up to 1 cycle (1 cycle is equal to 21 days)

Secondary Outcomes (1)

• Overall Response Rate

  Up to 3 years

Study Arms (1)

Treatment (Dinaciclib, Pembrolizumab)

EXPERIMENTAL

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

Drug: Dinaciclib; Drug: Pembrolizumab

Interventions

Dinaciclib DRUG

Given IV

Also known as: SCH727965

Treatment (Dinaciclib, Pembrolizumab)

Pembrolizumab DRUG

Given IV

Also known as: Keytruda

Treatment (Dinaciclib, Pembrolizumab)

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically documented, incurable, unresectable locally advanced, or metastatic breast cancer
• Histologically documented metastatic or locally advanced unresectable breast cancer that is ER and progesterone receptor (PR) \<10% expression and does not over-express Hormone Estrogen Receptor-Positive (HER2) protein (Immunohistochemistry (IHC) 0, 1+, or 2+ and Fluorescent in situ hybridization (FISH) \<2.0)
• Patient must consent to a biopsy of a site of disease unless the only site of disease is lung/pleura, bone, or deemed unsafe by the principal investigator
• Patient is male or female and ≥18 years of age on the day of signing informed consent.
• Patient must have performance status of 0-1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale and life expectancy \> 3 months
• Patient must have evaluable disease
• Patient must have adequate organ function as indicated by the following laboratory values:
• Hematological
• Absolute neutrophil count (ANC) ≥ 1,500 /μL
• Platelets ≥ 100,000 /μL
• Hemoglobin ≥ 9 g/dL
• Renal
• Serum creatinine or calculated creatinine clearance ≤ 1.5 x upper limit of normal (ULN) OR
• ≥ 60 mL/min for patients with creatinine levels \> 1.5 x institutional ULN
• Hepatic

You may not qualify if:

• Patient who has had radiotherapy within 1 week (or unresolved radiation-related toxicities), chemotherapy within 2 weeks or 5 half-lives, whichever is longer (6 weeks for nitrosoureas, mitomycin C or bevacizumab), anti-cancer monoclonal antibody for direct anti-neoplastic treatment within 3 weeks, or who has not recovered from toxicity due to previous agents administered. If the patient has residual toxicity from prior treatment, toxicity must be ≤ Grade 1 (except for neuropathy and alopecia).
• \> 2 lines of prior chemotherapy in the metastatic setting
• Serum lactate dehydrogenase (LDH) \> 1.5x institutional ULN
• Patients less than 2 weeks post major surgical procedure (all surgical wounds must be fully healed). For the purpose of this criterion, a major surgical procedure is defined as one requiring the administration of general anesthesia.
• Patient is currently participating in a study with an investigational compound or device.
• Patient has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. However, patients with CNS metastases who have completed a course of therapy would be eligible for the study provided they are clinically stable for at least 4 weeks prior to entry as defined as: (1) no evidence of new or enlarging CNS metastasis on brain imaging within 4 weeks of enrollment (2) off steroids for 2 weeks. Patients with clinically insignificant brain metastases that do not require treatment are eligible.
• Patient has a primary central nervous system tumor
• Patient has known hypersensitivity to the components of study drug or its analogs.
• Patient has a history or current evidence of clinically significant heart disease including:
• Clinically significant congestive heart failure, unstable angina pectoris,
• Clinically significant cardiac arrhythmia,
• Myocardial infarction during the last 6 months, and/or a current ECG tracing that is abnormal in the opinion of the treating Investigator,
• QTc prolongation \>480 msec (Bazett's Formula),
• Congenitally long QT syndrome, and/or current anti-arrhythmic therapy
• Patient with evidence of clinically significant bradycardia (HR \<50), or a history of clinically significant bradyarrhythmias such as sick sinus syndrome, 2nd degree atrioventricular (AV) block (Mobitz Type 2), Patient with uncontrolled hypertension (≥140/90 mmHg). Patients who are controlled on antihypertensive medication will be allowed to enter the study.

Sponsors & Collaborators

• Jo Chien: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

dinaciclib; pembrolizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• A. Jo Chien, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: UCSF Assistant Clinical Professor

Study Record Dates

• First Submitted: August 24, 2012
• First Posted: August 31, 2012
• Study Start: December 28, 2016
• Primary Completion: June 30, 2020
• Study Completion: February 28, 2022
• Last Updated: September 21, 2022

Record last verified: 2022-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)