Clinical trial NCT03121352: Carboplatin, Nab-Paclitaxel and Pembrolizumab for Metastatic Triple-Negative Breast Cancer
Official title: Pilot Study of Carboplatin, Nab-Paclitaxel and Pembrolizumab for Metastatic Triple-Negative Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Triple Negative Breast Cancer
Keywords: Carboplatin
Nab-Paclitaxel
Pembrolizumab
Lead sponsor: Case Comprehensive Cancer Center
Sponsor class: OTHER
First posted: 2017-04-20
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to see how effective the combination of the two chemotherapy drugs (carboplatin and nab-paclitaxel) are when added to a third drug, pembrolizumab.

Pembrolizumab is an investigational (experimental) drug that works by reinvigorating the immune system, allowing it to target and destroy cancer cells. Pembrolizumab is experimental because it is not approved by the Food and Drug Administration (FDA) for this type of breast cancer treatment.

Detailed description: Primary Objective - Determine overall response rate (ORR) in patients treated with CNP

Secondary Objective(s)

* Determine progression-free survival (PFS), and disease control rate (DCR) in patients treated with CNP.
* Determine duration of response in patients treated with CNP.
* Determine safety/tolerability of CNP.

Correlative Endpoints

- Identify pathologic and genomic correlates of response to CNP.

Study design including dose escalation / cohorts This is prospective pilot clinical trial of CNP in up to 30 patients with mTNBC

Eligibility criteria: Inclusion Criteria:

* Subjects must have histologically or cytologically confirmed metastatic triple negative breast cancer
* Subjects must have received no more than 2 prior therapies for this disease
* ECOG Performance Status 0-1
* Subjects must have normal organ and marrow function as defined below:

  * Hemoglobin ≥ 10.0 g/dl
  * Absolute neutrophil count ≥ 1,000/μL
  * Platelet count ≥ 100,000/μL
  * Total bilirubin within normal institutional limits
  * AST (SGOT) ≤ 2.5 X institutional upper limit of normal
  * ALT (SGPT) ≤ 2.5 X institutional upper limit of normal
  * Serum creatinine ≤ 1.5 normal institutional limits
* Life expectancy of 12 weeks or more
* Subjects must have the ability to understand and the willingness to sign a written informed consent document
* Subjects must have measurable disease per RECIST v1.1
* Subjects must be willing to undergo a preliminary biopsy of a metastatic focus for research purposes. A second post-treatment biopsy will be offered but will not be mandated

Exclusion Criteria:

* Prior treatment toxicities have not resolved to ≤ Grade 1 according to NCI CTCAE Version 4.0 (except for alopecia and neuropathy)
* Subjects receiving any other investigational agents
* Subjects with radiographically stable treated brain metastases are eligible but must not have been on steroid therapy for at least 4 weeks
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to nab-paclitaxel, carboplatin, pembrolizumab, or other agents used in this study
* Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
* Pregnant or breastfeeding women are excluded from this study
* Patients with conditions requiring immunosuppressive medications or chronic infections (including HIV infection, hepatitis B and C)
* Patients with chronic autoimmune disease
* Patients with prior therapy with antibodies that modulate T-cell function (e.g., anti-PD-1, anti-PD-L1)
* Patients with evidence of active, non-infectious pneumonia
* Patients active infection requiring intravenous systemic therapy
* Patients with known psychiatric or substance abuse disorders that would interfere with cooperation with requirements of the trial
* Patients who have received a live vaccine within 30 days prior to the first dose of pembrolizumab
* Patients with a known additional malignancy that is progressing or requires active treatment (within the last 5 years). Exceptions: basal cell carcinoma of the skin, squamous cell carcinoma of the skin or in situ cervical cancer that has undergone potentially curative therapy
* Patients who have received monoclonal anti-cancer antibody within 4 weeks of first dose of study drugs
* Patients who have received chemotherapy, small molecule targeted therapy or radiation within the 2 weeks of first dose of study drugs
* Patients who have participated in MK-3475 Merck studies
* Patients with carcinomatous meningitis

Primary outcomes:
measure: Overall Response Rate (ORR) in Patients Treated With CNP
timeFrame: Up to 24 months
Secondary outcomes:
measure: Progression-free Survival (PFS) in Patients Treated With CNP
timeFrame: Up to 24 months
measure: Disease Control Rate (DCR) in Patients Treated With CNP
timeFrame: Up to 24 months
measure: Duration of Response in Patients Treated With CNP
timeFrame: Up to 24 months
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center, Seidman Cancer Center, Case Comprehensive Cancer Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
state: Ohio
Study officials:
affiliation: University Hospitals Cleveland Medical Center, Seidman Cancer Center, Case Comprehensive Cancer Center
name: Joseph Baar, MD
role: PRINCIPAL_INVESTIGATOR
References: