Metastatic Triple Negative Breast Cancer
Conditions
Keywords
Carboplatin, Nab-Paclitaxel, Pembrolizumab
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
Interventions
DRUGCarboplatin
AUC 4.5 IV day 1 of 21-day cycle
DRUGNab-paclitaxel
75mg/m2 IV days 1, 8 and 15 of 21-day cycle
DRUGPembrolizumab
200 mg IV every 21 days
Sponsors
Case Comprehensive Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) in Patients Treated With CNP | Up to 24 months | The number of people with tumor responses according to RECIST (V1.1). These responses include Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival (PFS) in Patients Treated With CNP | Up to 24 months | Average time (in months) patient's tumors did not progress according to the RECIST criteria (V1.1). Progressive disease is defined as Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm |
| Disease Control Rate (DCR) in Patients Treated With CNP | Up to 24 months | the percentage of patients with advanced or metastatic cancer who have achieved complete response, partial response and stable disease to a therapeutic intervention. Responses are defined as Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm or Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study |
| Duration of Response in Patients Treated With CNP | Up to 24 months | Average time patients have a response, as defined by the RECIST criteria (V1.1). Response includes: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm or Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Carboplatin + Nab-paclitaxel + Pembrolizumab Combination therapy of Carboplatin, Nab-paclitaxel, and Pembrolizumab
Carboplatin: AUC 4.5 IV day 1 of 21-day cycle
Nab-paclitaxel: 75mg/m2 IV days 1, 8 and 15 of 21-day cycle
Pembrolizumab: 200 mg IV every 21 days | 30 |
| Total | 30 |
Baseline characteristics
| Characteristic | Carboplatin + Nab-paclitaxel + Pembrolizumab |
|---|---|
| Age, Customized 30-39 years | 2 participants |
| Age, Customized 40-49 years | 7 participants |
| Age, Customized 50-59 years | 11 participants |
| Age, Customized 60-69 years | 4 participants |
| Age, Customized 70-79 years | 5 participants |
| Age, Customized 80-89 years | 1 participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 30 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 24 Participants |
| Region of Enrollment United States | 30 participants |
| Sex: Female, Male Female | 30 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 27 / 30 |
| other Total, other adverse events | 30 / 30 |
| serious Total, serious adverse events | 13 / 30 |
Outcome results
Primary
Overall Response Rate (ORR) in Patients Treated With CNP
The number of people with tumor responses according to RECIST (V1.1). These responses include Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study
Time frame: Up to 24 months
Population: All participants who were evaluable for clinical response. Three participants were not evaluable for treatment response per Principal Investigator's assessment
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Carboplatin + Nab-paclitaxel + Pembrolizumab | Overall Response Rate (ORR) in Patients Treated With CNP | Complete Response (CR) | 2 Participants |
| Carboplatin + Nab-paclitaxel + Pembrolizumab | Overall Response Rate (ORR) in Patients Treated With CNP | Partial Response (PR) | 11 Participants |
| Carboplatin + Nab-paclitaxel + Pembrolizumab | Overall Response Rate (ORR) in Patients Treated With CNP | Progressive Disease (PD) | 6 Participants |
| Carboplatin + Nab-paclitaxel + Pembrolizumab | Overall Response Rate (ORR) in Patients Treated With CNP | Stable Disease (SD) | 8 Participants |
Secondary
Disease Control Rate (DCR) in Patients Treated With CNP
the percentage of patients with advanced or metastatic cancer who have achieved complete response, partial response and stable disease to a therapeutic intervention. Responses are defined as Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm or Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study
Time frame: Up to 24 months
Population: All participants who were evaluable for clinical response. Three participants were not evaluable for treatment response per Principal Investigator's assessment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Carboplatin + Nab-paclitaxel + Pembrolizumab | Disease Control Rate (DCR) in Patients Treated With CNP | 21 Participants |
Secondary
Duration of Response in Patients Treated With CNP
Average time patients have a response, as defined by the RECIST criteria (V1.1). Response includes: Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm or Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: Up to 24 months
Population: Participants who have a CR and PR response from treatment
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Carboplatin + Nab-paclitaxel + Pembrolizumab | Duration of Response in Patients Treated With CNP | Partial | 6.3 Months |
| Carboplatin + Nab-paclitaxel + Pembrolizumab | Duration of Response in Patients Treated With CNP | Complete | NA Months |
Secondary
Progression-free Survival (PFS) in Patients Treated With CNP
Average time (in months) patient's tumors did not progress according to the RECIST criteria (V1.1). Progressive disease is defined as Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm
Time frame: Up to 24 months
Population: All participants who received treatment.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Carboplatin + Nab-paclitaxel + Pembrolizumab | Progression-free Survival (PFS) in Patients Treated With CNP | 5.8 months |