Clinical Trials /

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

NCT04007588

Description:

This research study is studying different immunotherapy regimens as a possible treatment for stage III or IV resectable melanoma.

Related Conditions:
  • Cutaneous Melanoma
Recruiting Status:

Withdrawn

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: 19-043
  • NCT ID: NCT04007588

Conditions

  • Melanoma Stage III
  • Melanoma Stage IV

Interventions

DrugSynonymsArms
NivolumabOPDIVONivolumab+BMS-986205
BMS-986205Nivolumab+BMS-986205
IpilimumabYERVOYNivolumab+Ipilimumab

Purpose

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
    

Trial Arms

NameTypeDescriptionInterventions
Nivolumab+BMS-986205ExperimentalNivolumab will be administered intravenously Day 1 of each 28 day cycle. BMS-986205 will be administered orally on a daily basis
  • Nivolumab
  • BMS-986205
NivolumabExperimental-Nivolumab will be administered intravenously Day 1 of each 28 day cycle.
  • Nivolumab
Nivolumab+IpilimumabExperimentalNivolumab will be administered intravenously Day 1 of each 28 day cycle. Ipilimumab will be administered intravenously every 6 weeks
  • Nivolumab
  • Ipilimumab

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

               -  creatinine within normal institutional limits OR

               -  creatinine clearance ≥40 mL/min/1.73 m2 for participants with creatinine levels
                  above institutional normal.

               -  C-Reactive Protein < institutional ULN

          -  Quantitative or qualitative G6PD assay results must not suggest underlying G6PD
             deficiency

          -  Measurable disease (by CT, PET/CT or MRI)

          -  Prior therapies including targeted therapy and immunotherapy are not allowed, with the
             exception of adjuvant Ipilimumab or Interferon-α-2b.

          -  Ability to understand and the willingness to sign a written informed consent document.

          -  Ability to swallow pills intact and without GI issues which may impact medication
             absorption.

          -  Women of childbearing potential (WOCBP) must agree to follow instructions for
             method(s) of contraception (Refer to Appendix B) for the duration of treatment with
             study treatment(s) plus 5 months post-treatment completion (i.e. 30 days plus the time
             required for nivolumab to undergo approximately 5 half-lives).

          -  Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy
             test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to
             the start of study treatment.

          -  Males who are sexually active with WOCBP must agree to follow instructions for
             method(s) of contraception for the duration of treatment with study treatment(s) plus
             7 months post-treatment completion (i.e. 90 days plus the time required for nivolumab
             to undergo approximately 5 half-lives). In addition, male participants must be willing
             to refrain from sperm donation during this time. This criterion applies to azoospermic
             males as well.

        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-986205. 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-986205. These potential risks may also apply to other agents
             used in this study.

          -  Known active HIV, Hepatitis B or Hepatitis C patients. HIV-positive participants on
             combination antiretroviral therapy are ineligible because of the potential for an
             immunologic effect with the therapy. Appropriate studies will be undertaken in
             participants receiving combination antiretroviral therapy when indicated.

          -  Autoimmune disease that requires treatment at the time of enrollment. Participants
             with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin
             disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment
             or conditions not expected to recur in the absence of an external trigger are
             permitted to enroll.

          -  Participant with a personal or family (ie, in a first-degree relative) history of
             cytochrome b5 reductase deficiency (previously called methemoglobin reductase
             deficiency) or other diseases that put them at risk of methemoglobinemia. All
             participants will be screened for methemoglobin levels prior to randomization.

          -  Participant with a history of G6PD deficiency or other congenital or autoimmune
             hemolytic disorders. All participants will be screened for G6PD levels prior to
             randomization.

          -  Participants must not have a history of life-threatening toxicity related to prior
             immune therapy (eg. anti-CTLA-4 or any other antibody or drug specifically targeting
             T-cell co-stimulation or immune checkpoint pathways) except those that are unlikely to
             re-occur with standard countermeasures (eg. hormone replacement after adrenal crisis).

          -  Treatment with botanical preparations (eg, herbal supplements or traditional Chinese
             medicines) intended for general health support or to treat the disease under study
             within 2 weeks prior to randomization.

          -  History of other malignancy within 3 years prior to screening, with the exception of
             those with a negligible risk of metastasis or death (e.g., 5-year OS of > 90%), such
             as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma,
             localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer.

          -  Participants who have had major surgery requiring general anesthesia or significant
             trauma who have not recovered per physician determination for at least 14 days prior
             to randomization.

          -  Participants with conditions known to interfere significantly with the absorption of
             oral medication, as per investigator judgment.

          -  Participants with uncontrolled adrenal insufficiency.

          -  Prior history of serotonin syndrome.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Major Pathologic Response Rate
Time Frame:2 years
Safety Issue:
Description:Complete Pathological response rate or near pathological complete response rate on each treatment arm

Secondary Outcome Measures

Measure:Recurrence free survival
Time Frame:2 years
Safety Issue:
Description:Time from treatment start to recurrence of melanoma
Measure:Overall Survival Rate
Time Frame:2 years
Safety Issue:
Description:Time from treatment start to death
Measure:Changes In Infiltrating immune cells From Pre-Treatment To Time Of Excision
Time Frame:2 Years
Safety Issue:
Description:Changes in immune cells in the tumor micro environment including CD8 T-cells
Measure:Rates of adverse events and serious adverse events on the different treatment arms.
Time Frame:2 years
Safety Issue:
Description:Rates of different grade adverse events on each treatment arm

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Dana-Farber Cancer Institute

Trial Keywords

  • Melanoma

Last Updated