A Phase II Trial of Neoadjuvant Treatment With PD-1 Inhibition (Nivolumab) With or Without IDO Inhibition (BMS-986205) and With or Without CTLA-4 Inhibition (Ipilimumab) in Resectable Stage III or IV Melanoma
Overview
- Phase
- Phase 2
- Intervention
- Nivolumab
- Conditions
- Melanoma Stage III
- Sponsor
- Dana-Farber Cancer Institute
- Locations
- 2
- Primary Endpoint
- Major Pathologic Response Rate
- Status
- Withdrawn
- Last Updated
- 6 years ago
Overview
Brief Summary
This research study is studying different immunotherapy regimens as a possible treatment for stage III or IV resectable melanoma.
Detailed Description
This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means the drug is being studied. The FDA (the U.S. Food and Drug Administration) has approved OPDIVO® (nivolumab), YERVOY® (ipilimumab), and a combination of the two as treatment options for metastatic melanoma. The FDA (the U.S. Food and Drug Administration) has not approved the combination of nivolumab and BMS-986205 as a treatment for any disease. This research study is looking for more information on the efficacy the combination of nivolumab and BMS-986205 in the treatment of melanoma. Nivolumab, Ipilimumab, and BMS-986205 are types of immunotherapy. Immunotherapy works by encouraging the body's own immune system to attack the cancer cells. Nivolumab, Ipilimumab, and BMS-986205 work by stopping various molecules on cancer cells and body cells from working against the immune system's natural fight against cancer. In this research study, the investigators are going to look at the following while the participants are receiving the study drug(s): • The effectiveness (how well the drug works), safety, and tolerability of Nivolumab, BMS-986205 and Nivolumab, and Ipilimumab and Nivolumab in people with resectable stage III or IV melanoma
Investigators
Elizabeth Buchbinder
Principal Investigator
Dana-Farber Cancer Institute
Eligibility Criteria
Inclusion Criteria
- •Histologic or cytologic diagnosis of resectable stage III or IV cutaneous melanoma. Patients with melanoma of mucosal origin are not eligible. Patients with acral melanoma that fit criteria are eligible. Patients must have clinically detectable stage III (clinically detectable N1b, N1c, N2b, N2c, N3b or N3c) or stage IV resectable melanoma.
- •Age ≥ 18 years.
- •ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A)
- •Participants must have normal organ and marrow function as defined below:
- •leukocytes ≥2,000/mcL
- •absolute neutrophil count ≥1,500/mcL
- •platelets ≥100,000/mcL
- •hemoglobin ≥9.0g/dL
- •total bilirubin within normal institutional limits
- •AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal
Exclusion Criteria
- •A history of prior treatment with PD-1 inhibitor, CTLA-4 inhibitor or IDO inhibition. Prior therapy with ipilimumab or Interferon-α-2b in the adjuvant setting is permitted. Participants may not have received live/attenuated vaccines within 30 days of first treatment.
- •Participants with uveal or mucosal melanoma
- •Participants with known brain metastases must have documented stability for at least 30 days directly prior to study enrollment and not be requiring active treatment for these. Prior radiation, surgery and stereotactic radiosurgery are allowed but must be completed four weeks prior to initiating therapy.
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to nivolumab, ipilimumab, methylene blue or BMS-
- •History or presence of hypersensitivity or idiosyncratic reaction to methylene blue.
- •Need for systemic steroids at the time of enrollment. Physiologic replacements at a dose of less than 10 mg daily prednisone equivalent is allowed.
- •Blood Methemoglobin \> ULN, assessed in an arterial or venous blood sample or by co-oximetry
- •Participants with active ILD/pneumonitis or history of ILD/ pneumonitis requiring steroids.
- •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 women are excluded from this study because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with nivolumab or BMS-986205, breastfeeding should be discontinued if the mother is treated with nivolumab or BMS-
Arms & Interventions
Nivolumab+BMS-986205
* Nivolumab will be administered intravenously Day 1 of each 28 day cycle. * BMS-986205 will be administered orally on a daily basis
Intervention: Nivolumab
Nivolumab+BMS-986205
* Nivolumab will be administered intravenously Day 1 of each 28 day cycle. * BMS-986205 will be administered orally on a daily basis
Intervention: BMS-986205
Nivolumab
-Nivolumab will be administered intravenously Day 1 of each 28 day cycle.
Intervention: Nivolumab
Nivolumab+Ipilimumab
* Nivolumab will be administered intravenously Day 1 of each 28 day cycle. * Ipilimumab will be administered intravenously every 6 weeks
Intervention: Nivolumab
Nivolumab+Ipilimumab
* Nivolumab will be administered intravenously Day 1 of each 28 day cycle. * Ipilimumab will be administered intravenously every 6 weeks
Intervention: Ipilimumab
Outcomes
Primary Outcomes
Major Pathologic Response Rate
Time Frame: 2 years
Complete Pathological response rate or near pathological complete response rate on each treatment arm
Secondary Outcomes
- Recurrence free survival(2 years)
- Overall Survival Rate(2 years)
- Changes In Infiltrating immune cells From Pre-Treatment To Time Of Excision(2 Years)
- Rates of adverse events and serious adverse events on the different treatment arms.(2 years)