Phase 2 Trial of Dose Dense (Weekly) Paclitaxel With Pembrolizumab (MK-3475) in Platinum Resistant Recurrent Ovarian Cancer
Overview
- Phase
- Phase 2
- Intervention
- Pembrolizumab
- Conditions
- Ovarian Cancer
- Sponsor
- H. Lee Moffitt Cancer Center and Research Institute
- Enrollment
- 42
- Locations
- 3
- Primary Endpoint
- Progression-free Survival (PFS) at 6 Months
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
The purpose of this study is to find out if the combination of Paclitaxel once per week with Pembrolizumab once every 3 weeks will help participants with this disease. Researchers want to find out the effectiveness of the drug combination to improve the delay of cancer progression or death and compare it to historical data for weekly paclitaxel alone, and assess safety.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Must have confirmation of the histologic diagnosis of high-grade (grade 2-3) epithelial, non-mucinous, non-borderline, ovarian, fallopian tube, or primary peritoneal carcinoma. May be based on original pathology report or review of original slides.
- •Willing and able to provide written informed consent/assent and authorization
- •≥ 18 years of age on day of signing informed consent
- •Disease must have been persistent or have recurred within 6 months of prior platinum therapy. Disease may not have progressed during prior platinum therapy (i.e., refractory).
- •Have measurable disease or detectable (non-measureable) disease
- •Measurable disease: must have at least one "target lesion" to be used to assess response on this protocol.
- •Prior Therapy:
- •Have had one prior platinum-based chemotherapeutic regimen for management of primary disease containing carboplatin, cisplatin, or another organoplatinum compound. This initial treatment may have included intraperitoneal therapy, consolidation, non-cytotoxic agents (biologic/ targeted) or extended therapy administered after surgical or non-surgical assessment. If patients were treated initially with paclitaxel for their primary disease, this can have been given weekly or every 3 weeks. The most recent therapy and any therapies subsequent to initial therapy, however, cannot have contained weekly paclitaxel. If the immediate prior (most recent therapy) is the initial therapy, it may not have been with weekly paclitaxel.
- •Allowed to receive (not required to receive), 2 additional cytotoxic regimens for management of recurrent or persistent disease, with no more than 1 non-platinum regimen. Treatment with weekly paclitaxel for recurrent or persistent disease is NOT allowed.
- •Allowed to receive(not required to receive), non-cytotoxic (biologic/targeted) therapy as part of their primary treatment regimen. Allowed to receive (not required to receive), non-cytotoxic (biologic/targeted) therapy as part of their treatment for recurrent or persistent disease and/or as treatment for recurrent or persistent disease. If non-cytotoxic (biologic/targeted) therapy is given alone (i.e., not in combination with cytotoxic chemotherapy) it will NOT count as a prior regimen.
Exclusion Criteria
- •Have low-grade or non-epithelial cancers, mucinous cancers, and/or borderline low-malignant potential cancers
- •Currently participating in/have participated in a study of an investigational agent or is or has been using an investigational device within 4 weeks of the first dose of treatment
- •Diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
- •Had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to prior therapies
- •Had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 3 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent. - Note: If received major surgery, must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
- •History of other invasive malignancies (with exception of non-melanoma skin cancer and or in situ cancers that have undergone potentially curative therapy) are excluded if there is any evidence of other malignancy being present within the last 3 years. Patients are also excluded if their previous cancer treatment contraindicates this protocol therapy.
- •Have received prior radiotherapy to any portion of the abdominal cavity or pelvis OTHER THAN for the treatment of ovarian, fallopian tube, or primary peritoneal cancer within the last 3 years are excluded. Prior radiation for localized cancer of the breast, head and neck, or skin is permitted, provided that it was completed more than 3 years prior to registration, and the patient remains free of recurrent or metastatic disease.
- •Have received prior chemotherapy for any abdominal or pelvic tumor OTHER THAN for the treatment of ovarian, fallopian tube, or primary peritoneal cancer within the last 3 year. May have received prior adjuvant chemotherapy for localized breast cancer, provided that it was completed more than 3 years prior to registration, and the patient remains free of recurrent or metastatic disease.
- •History of synchronous endometrial cancer unless all of the following conditions are met: Stage not greater than I-A (FIGO 2010 staging criteria); no more than superficial myometrial invasion (\<50%), without vascular or lymphatic invasion; no poorly differentiated subtypes, including papillary serous, clear cell or other FIGO Grade 3 lesions and it has been greater than 3 years since diagnosis and there have been no recurrences.
- •Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to the first dose of trial 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 trial treatment.
Arms & Interventions
Combination Therapy
Combination Therapy: Pembrolizumab (experimental use) and Paclitaxel (standard use). All trial treatments will be administered on an outpatient basis. One cycle equals 21 days. The first cycle is 28 days with Pembrolizumab given on day 8 in order to determine paclitaxel tolerance.
Intervention: Pembrolizumab
Combination Therapy
Combination Therapy: Pembrolizumab (experimental use) and Paclitaxel (standard use). All trial treatments will be administered on an outpatient basis. One cycle equals 21 days. The first cycle is 28 days with Pembrolizumab given on day 8 in order to determine paclitaxel tolerance.
Intervention: Paclitaxel
Outcomes
Primary Outcomes
Progression-free Survival (PFS) at 6 Months
Time Frame: 6 months
6-month progression-free survival of the combination of weekly paclitaxel with pembrolizumab (MK-3475) for those patients who received treatment and were evaluable (had one response assessment scan by RECIST 1.1) . 6-month PFS: The proportion of patients at 6 months alive without progressive disease. Progressive Disease (PD): Sum of the longest diameters (SLD) increased by at least 20% from the smallest value on study (including baseline, if that is the smallest).
Occurrence of Adverse Events
Time Frame: 2 years, 6 months
Safety of the combination of paclitaxel weekly with pembrolizumab every 3 weeks (Q3W). Serious Adverse Events and Adverse Events will be reported in that Results Data section, according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) V4.0.
Secondary Outcomes
- Response Rate (RR)(Up to 36 months)
- Disease Control Rate (DCR)(Up to 36 months)
- Duration of Response (DOR)(Up to 36 months)
- Median Overall Survival (OS)(Up to 36 months)