A Study of Carboplatin and Paclitaxel Chemotherapy With Nivolumab With or Without Ipilimumab in Patients With Ovarian Cancer

NCT03245892 | Completed Phase 1 FDA Drug

• 1 other identifier: 17-182
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to find out what effects, good or bad, the addition of nivolumab or the combination of nivolumab plus ipilimumab to typical chemotherapy has on the treatment of advanced high-grade serous cancers of ovarian, fallopian tube, or primary peritoneal origin. The typical chemotherapy treatment is Carboplatin and Paclitaxel.

Conditions

High Grade Serous Ovarian; Fallopian Tube; Primary Peritoneal Cancer

Keywords

Nivolumab; Paclitaxel; Carboplatin; 17-182

Outcome Measures

Primary Outcomes (2)

• number of patients with dose limiting toxicities with weekly paclitaxel/carboplatin plus nivolumab

  The safety of this regimen will be assessed by determination of the DLTs observed in the study population. If \>=3/10 DLTs are seen we will deem the regimen not safe and stop the trial early. If \>=5/20 patients have DLTs the treatment regimen would be deemed unsafe. Enrollment will be halted after 10 patients have accrued until all 10 patients have cleared the DLT period of 6 weeks

  6 weeks

• number of patients with dose limiting toxicities weekly paclitaxel/carboplatin plus nivolumab and ipilimumab

  The safety of this regimen will be assessed by determination of the DLTs observed in the study population. If \>=3/10 DLTs are seen we will deem the regimen not safe and stop the trial early. If \>=5/20 patients have DLTs the treatment regimen would be deemed unsafe. Enrollment will be halted after 10 patients have accrued until all 10 patients have cleared the DLT period of 6 weeks

  6 weeks

Study Arms (2)

Carboplatin and Paclitaxel Chemotherapy With Nivolumab (Closed)

EXPERIMENTAL

Patients will be treated with nivolumab plus standard of care dose dense paclitaxel and carboplatin for three cycles, where each cycle is 3 weeks, followed by cytoreductive surgery then three more cycles of the same treatment regimen administered as adjuvant treatment. Paclitaxel 80mg/m2 will be administered over approximately 1 hour as an IV infusion on Days 1,8, and 15 of each 21-day cycle. Carboplatin AUC6 will be administered as approximately a 30 minute IV infusion, following paclitaxel administration on Day 1 of each 21-day cycle. Carboplatin dose calculation instructions can be found in Appendix 4. Nivolumab 360mg will be infused IV over approximately 30min on Day 1 of Cycles 1-6. During the maintenance phase, Nivolumab 480mg will be infused IV on day 1 of each 28 day cycle, for up to 12 months. During the maintenance period, each cycle is 4 weeks.

Drug: Carboplatin and Paclitaxel; Drug: Nivolumab; Procedure: Cytoreductive surgery

Nivolumab plus Ipilimumab plus Paclitaxel & Carboplatin

EXPERIMENTAL

Patients will be treated with nivolumab plus ipilimumab plus standard of care dose dense paclitaxel \& carboplatin chemotherapy for 3 cycles (up to a maximum of six), each cycle is 3 weeks, followed by cytoreductive surgery then three more cycles of the same treatment regimen. Paclitaxel 80mg/m2 IV will be administered over approx 1 hour on Days 1,8, \& 15 of each 21 day cycle. Carboplatin AUC6 will be administered as an approx 30 minute IV infusion, following paclitaxel admin on Day 1 of each 21 day cycle. Nivolumab 360mg will be infused IV over approx 30 min on Day 1 of Cycles 1-6 (to 9) of each 21 day cycle. Ipilimumab 1mg/kg will be infused IV over approx 30 min on Day 1 of Cycles 1 \& 3, as well as Cycle 4 \& Cycle 6. Of note, if patients receive more than 3 cycles in the pre-operative setting, then ipilimumab will be administered with the first \& third cycle in the post-operative setting. Nivolumab will then be infused Day 1 of each 28 day maintenance phase cycle.

Drug: Carboplatin and Paclitaxel; Drug: Nivolumab; Procedure: Cytoreductive surgery; Drug: Ipilimumab

Interventions

Carboplatin and Paclitaxel DRUG

Paclitaxel 80mg/m2 will be administered over approximately 1 hour as an IV infusion on Days 1,8, and 15 of each 21-day cycle. Carboplatin AUC6 will be administered as approximately a 30 minute IV infusion, following paclitaxel administration on Day 1 of each 21-day cycle.

Carboplatin and Paclitaxel Chemotherapy With Nivolumab (Closed); Nivolumab plus Ipilimumab plus Paclitaxel & Carboplatin

Cytoreductive surgery PROCEDURE

Cytoreductive surgery

Carboplatin and Paclitaxel Chemotherapy With Nivolumab (Closed); Nivolumab plus Ipilimumab plus Paclitaxel & Carboplatin

Ipilimumab DRUG

Ipilimumab 1mg/kg every 6 weeks x 3-6 cycles in the neoadjuvant setting (maximum 2 doses of ipilimumab)

Nivolumab plus Ipilimumab plus Paclitaxel & Carboplatin

Nivolumab DRUG

Nivolumab 360mg will be infused IV over approximately 30 min on Day 1 of Cycles 1-6 (to 8) of each 21 day cycle. During the maintenance phase, Nivolumab 480mg will be infused IV over approximately 30 min on day 1 of each 28 day cycle, for up to 12 months. During the maintenance period, each cycle is 4 weeks

Carboplatin and Paclitaxel Chemotherapy With Nivolumab (Closed); Nivolumab plus Ipilimumab plus Paclitaxel & Carboplatin

Eligibility Criteria

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

You may qualify if:

• Patients must have clinically and radiographically suspected International Federation of Gynecology and Obstetrics (FIGO) stage (Appendix 2) 3 or 4 high grade serous ovarian, primary peritoneal or fallopian tube cancer, high grade, for whom the plan of management will include neoadjuvant chemotherapy (NACT) with interval tumor reductive surgery (TRS). Patients will be selected for NACT according to established criteria (Society of Gynecologic Oncology and the American Society of Clinical Oncology Guideline, https://www.ncbi.nlm.nih.gov/pubmed/27650684). Patients must have undergone core needle biopsy for histologic confirmation prior to start of treatment. See Appendix 3 for guidelines to aid in histologic diagnosis.
• Institutional confirmation of pathology on or laparoscopic biopsy performed at MSKCC with sufficient tissue for analysis or willingness to undergo repeat laproscopic biopsy if diagnostic biopsy was performed at an outside hospital.
• Appropriate stage for study entry based on the following diagnostic workup:
• History/physical examination within 28 days prior to registration;
• CT imaging of the chest, abdomen and pelvis within 28 days prior to registration documenting disease consistent with FIGO stage III or IV disease (patients who cannot receive contrast may instead undergo MRI of abdomen and pelvis along with non-contrast chest CT);
• Further protocol-specific assessments as detailed below.
• Age ≥18
• ECOG Status of 0, 1, or 2 within 28 days prior to registration.
• Adequate hematologic function within 14 days prior to registration defined as follows:
• ANC ≥1,000/mcl. This ANC cannot have been induced by granulocyte colony stimulating factors.
• Platelets ≥75,000/mc
• Hemoglobin ≥8.0 mg/dl (transfusions are permitted to achieve baseline hemoglobin level)
• Adequate renal function within 14 days prior to registration defined as follows:
• °Creatinine \<=1.5 x ULN.
• Adequate hepatic function within 14 days prior to registration defined as follows:

You may not qualify if:

• Subjects with a history of other invasive malignancies, with the exception of non-melanoma skin cancer, are excluded if there is any evidence of other malignancy being present within the last 3 years. Subjects are also excluded if their previous cancer treatment contraindicates this protocol's therapy.
• Patients who have received prior radiotherapy to any portion of the abdominal cavity or pelvis or thoracic cavity within the last three 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 three years prior to registration, and the patient remains free of recurrent or metastatic disease.
• Patients who have received any prior treatment for management of their epithelial ovarian, fallopian tube or peritoneal primary cancer.
• Patients with any histology other than high grade serous evident on pretreatment biopsy.
• Patients with synchronous primary endometrial cancer, or a past history of primary endometrial cancer, unless all of the following conditions are met: Stage not greater than I-A, grade 1 or 2, no more than superficial myometrial invasion, without vascular or lymphatic invasion; no poorly differentiated subtypes, including serous, clear cell or other FIGO grade 3 lesions.
• Severe, active co-morbidity defined as follows:
• Chronic or current active infectious disease requiring systemic antibiotics, antifungal or antiviral treatment (with the exception of uncomplicated UTI)
• Clinically significant cardiac disease including unstable angina, acute myocardial infarction within 6 months from enrollment, New York Heart Association Class III or IV congestive heart failure, and serious arrhythmia requiring medication (this does not include asymptomatic atrial fibrillation with controlled ventricular rate).
• Partial or complete gastrointestinal obstruction
• Patients with anticipated contraindications to interval tumor reductive surgery.
• Patients with any condition that in the judgment of the investigator would jeopardize safety or patient compliance with the protocol.
• Patients who are unwilling to be transfused with blood components.
• Concurrent anticancer non protocol directed therapy (e.g. chemotherapy, radiation therapy, biologic therapy, immunotherapy, hormonal therapy, investigational therapy).
• Receipt of an investigational study drug for any indication within 28 days or 5 half-lives (whichever is longer) prior to Day 1 of protocol therapy.
• Patients who, in the opinion of the investigator, are unable or unlikely to comply with the dosing schedule and study evaluations.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Interventions

Carboplatin; Paclitaxel; Nivolumab; Cytoreduction Surgical Procedures; Ipilimumab

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Surgical Procedures, Operative

Study Officials

• Carol Aghajanian, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single center, non-randomized, open label, pilot study to evaluate the safety and tolerability of neoadjuvant and post-surgical dose dense paclitaxel and carboplatin chemotherapy in combination with nivolumab for the treatment of advanced high grade serous cancers of ovarian, fallopian tube, or primary peritoneal origin.

Study Record Dates

• First Submitted: August 8, 2017
• First Posted: August 10, 2017
• Study Start: August 4, 2017
• Primary Completion: December 4, 2025
• Study Completion: December 4, 2025
• Last Updated: December 17, 2025

Record last verified: 2025-12

Locations

US (1)