Matched Paired Pharmacodynamics and Feasibility Study of Pembrolizumab in Combination With Chemotherapy in Frontline Ovarian Cancer
Overview
- Phase
- Phase 2
- Intervention
- Carboplatin
- Conditions
- Stage III Fallopian Tube Cancer AJCC v7
- Sponsor
- M.D. Anderson Cancer Center
- Enrollment
- 31
- Locations
- 5
- Primary Endpoint
- To Evaluate Progression-free Survival of Paclitaxel/Carboplatin and Pembrolizumab in Patients With Advanced Stage, Metastatic Ovarian Cancer Undergoing NACT
- Status
- Completed
- Last Updated
- 10 months ago
Overview
Brief Summary
This phase II trial studies how well pembrolizumab works when given in combination with carboplatin and paclitaxel in treating patients with stage III-IV ovarian, primary peritoneal, or fallopian tube cancer. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving pembrolizumab in combination with carboplatin and paclitaxel may be a better treatment for ovarian, primary peritoneal, or fallopian tube cancer.
Detailed Description
PRIMARY OBJECTIVES: I. To evaluate progression-free survival of paclitaxel/carboplatin and pembrolizumab in patients with advanced stage, metastatic ovarian cancer undergoing neoadjuvant chemotherapy (NACT). SECONDARY OBJECTIVES: I. To describe the feasibility of combination therapy with pembrolizumab in this population. II. To evaluate the safety of combination and maintenance pembrolizumab. III. To report overall survival. EXPLORATORY OBJECTIVES: I. To describe the sequential effects of chemotherapy on immune response and PD-1 expression and receptor occupancy. II. To evaluate circulating lymphoid populations (subsets). III. To determine tissue PD-L1 expression and T-cell infiltration. OUTLINE: NACT: Patients receive paclitaxel intravenously (IV) over 1 hour on days 1, 8, and 15, and carboplatin IV over 1 hour on day 1. Treatment repeats every 21 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery. ADJUVANT THERAPY: Beginning 3-6 weeks after surgery, paclitaxel IV over 1 hour on days 1, 8, and 15, patients receive carboplatin IV over 1 hour on day 1, and pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for 3 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 20 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 12 weeks.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Signed, written informed consent
- •Histology showing high-grade epithelial non-mucinous ovarian, primary peritoneal, or fallopian tube cancer
- •No more than 4 prior cycles of chemotherapy for primary advanced (stage III or IV) epithelial ovarian, primary peritoneal, or fallopian tube cancer
- •No prior treatment involving irradiation, hormonal therapy, immunotherapy, investigational therapy, and/or other concurrent agents or therapies for ovarian cancer
- •A disposition to neoadjuvant chemotherapy with planned interval tumor reductive surgery after 4 complete cycles of treatment
- •Planned dose-dense chemotherapy with combination carboplatin and paclitaxel given intravenously
- •Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.
- •Measurable disease is defined at least one lesion that can be accurately measured in at least one dimension (longest dimension to be recorded); each "target" lesion must be \>= 20 mm when measured by conventional techniques, including palpation, plain x-ray, computed tomography (CT), and magnetic resonance imaging (MRI), or \>= 10 mm when measured by spiral CT
- •Patients with non-measurable but evaluable solid tumors may be deemed eligible contingent upon principal investigator (PI) review
- •Peripheral neuropathy grade 0 or 1 by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
Exclusion Criteria
- •Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment
- •Histology showing mucinous or low grade epithelial ovarian carcinoma
- •History of another primary malignancy except for:
- •Malignancy treated with curative intent and with no known active disease \>= 5 years before the first dose of study drug and or low potential risk for recurrence
- •Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
- •Adequately treated carcinoma in situ without evidence of disease e.g., cervical cancer in situ
- •Concomitant stage 1A/B, grade 1-2 endometrioid endometrial cancer as allowable contemporary tumor
- •Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of study treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to study treatment
- •Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
- •Patients with ovarian cancer not medically fit for diagnostic laparoscopy prior to initiation of therapy
Arms & Interventions
Treatment (carboplatin, paclitaxel, and pembrolizumab)
NACT: Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15, and carboplatin IV over 1 hour on day 1. Treatment repeats every 21 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery. ADJUVANT THERAPY: Beginning 3-6 weeks after surgery, paclitaxel IV over 1 hour on days 1, 8, and 15, patients receive carboplatin IV over 1 hour on day 1, and pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for 3 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 20 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Carboplatin
Treatment (carboplatin, paclitaxel, and pembrolizumab)
NACT: Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15, and carboplatin IV over 1 hour on day 1. Treatment repeats every 21 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery. ADJUVANT THERAPY: Beginning 3-6 weeks after surgery, paclitaxel IV over 1 hour on days 1, 8, and 15, patients receive carboplatin IV over 1 hour on day 1, and pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for 3 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 20 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Laboratory Biomarker Analysis
Treatment (carboplatin, paclitaxel, and pembrolizumab)
NACT: Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15, and carboplatin IV over 1 hour on day 1. Treatment repeats every 21 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery. ADJUVANT THERAPY: Beginning 3-6 weeks after surgery, paclitaxel IV over 1 hour on days 1, 8, and 15, patients receive carboplatin IV over 1 hour on day 1, and pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for 3 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 20 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Paclitaxel
Treatment (carboplatin, paclitaxel, and pembrolizumab)
NACT: Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15, and carboplatin IV over 1 hour on day 1. Treatment repeats every 21 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery. ADJUVANT THERAPY: Beginning 3-6 weeks after surgery, paclitaxel IV over 1 hour on days 1, 8, and 15, patients receive carboplatin IV over 1 hour on day 1, and pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for 3 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 20 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Pembrolizumab
Treatment (carboplatin, paclitaxel, and pembrolizumab)
NACT: Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15, and carboplatin IV over 1 hour on day 1. Treatment repeats every 21 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients then undergo surgery. ADJUVANT THERAPY: Beginning 3-6 weeks after surgery, paclitaxel IV over 1 hour on days 1, 8, and 15, patients receive carboplatin IV over 1 hour on day 1, and pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for 3 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive pembrolizumab IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 20 cycles in the absence of disease progression or unacceptable toxicity.
Intervention: Pharmacological Study
Outcomes
Primary Outcomes
To Evaluate Progression-free Survival of Paclitaxel/Carboplatin and Pembrolizumab in Patients With Advanced Stage, Metastatic Ovarian Cancer Undergoing NACT
Time Frame: Up to 3 years
PFS was defined from the start of neoadjuvant therapy until the date of disease progression or death, whichever occurred first. Disease progression was evaluated using RECIST v1.1 guidelines. Patients who were alive without disease progression were censored at their last evaluation date or until withdrawal of consent. Patients who were removed off protocol for reasons other than disease progression, death, treatment toxicity, or withdrawal of consent were censored at the start date of their non-protocol treatment. Feasibility was defined as the ability to complete all planned 3 cycles of adjuvant carboplatin, paclitaxel, and pembrolizumab.
Secondary Outcomes
- To Describe the Feasibility of Combination Therapy and Maintenance Pembrolizumab in This Population(Up to 3 years)
- To Evaluate the Safety of Combination and Maintenance Pembrolizumab(up to 3 years)