A Phase I Trial of a Vaccine Combining Multiple Class I Peptides and Montanide ISA 51VG With Escalating Doses of Anti-PD-1 Antibody Nivolumab or Ipilimumab With Nivolumab For Patients With Resected Stages IIIC/ IV Melanoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by H. Lee Moffitt Cancer Center and Research Institute
Sponsor:
Collaborators:
Medarex
Bristol-Myers Squibb
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier:
NCT01176474
First received: August 5, 2010
Last updated: August 13, 2014
Last verified: August 2014
  Purpose

The purpose of this study is to test the side effects of an investigational vaccine with an immune booster, or 2 different boosters together. Investigators also want to find out its effects on the immune system and whether it will decrease the chance that melanoma will return.


Condition Intervention Phase
Melanoma (Skin)
Biological: NY-ESO-1 157-165 (165V)
Drug: Nivolumab
Biological: gp100:280-288 (288V)
Drug: Montanide ISA 51 vegetable grade (VG)
Drug: Ipilimumab
Procedure: Apheresis Procedure
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Trial of a Vaccine Combining Multiple Class I Peptides and Montanide ISA 51VG With Escalating Doses of Anti-PD-1 Antibody Nivolumab or Ipilimumab With Nivolumab For Patients With Resected Stages IIIC/ IV Melanoma

Resource links provided by NLM:


Further study details as provided by H. Lee Moffitt Cancer Center and Research Institute:

Primary Outcome Measures:
  • Time to Relapse [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    The primary efficacy analysis is time to relapse, to determine relapse at the end of each cycle (Weeks 12 and 24). Time to relapse will be summarized using descriptive statistics.


Secondary Outcome Measures:
  • Overall Survival (OS) [ Time Frame: 2 years, 6 months ] [ Designated as safety issue: No ]
    Overall survival will be the secondary efficacy endpoint.


Estimated Enrollment: 85
Study Start Date: July 2010
Estimated Study Completion Date: May 2015
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Nivolumab and Peptide Vaccine

Cohorts 1 through 3: Participants will receive nivolumab with the peptide vaccine within 8 days after their first apheresis procedure.

Vaccine Combining Multiple Class I Peptides and Montanide ISA 51 VG with Escalating Doses of Anti-PD-1 Antibody Nivolumab (BMS-936558). Level 1: 1 mg/kg Nivolumab + peptide vaccine. Level 2: 3 mg/kg Nivolumab + peptide vaccine. Level 3: 10 mg/kg Nivolumab + peptide vaccine.

Biological: NY-ESO-1 157-165 (165V)

The vaccine contains two peptides from two different proteins (peptides are pieces that make up proteins) called gpl00 and NY-ES0-1.

Route of Administration: When prepared as a vaccine emulsion with Montanide ISA 51 VG, the vaccine is given by deep subcutaneous injection.

Method of Administration: The 0.5 mg vaccine emulsion dose is administered as a 1 mL injection (0.5 mg/1 mL) as a deep subcutaneous injection in the anterior thigh of the same extremity. Injections should be separated by at least 3 cm to avoid the formation of coalescent granulomas. All 4 peptides (total of 6 injections) will be administered in the same thigh and alternating thighs will be used for each subsequent treatment.

Other Names:
  • NSC 717388
  • peptide vaccine
  • NY-ESO-1
  • ESO-165V Peptide
Drug: Nivolumab

Nivolumab (BMS-936558) is a fully human monoclonal antibody (HuMAb) against programmed death-1 (PD-1).

Nivolumab will be given at the following dosages: 1, 3, or 10 mg/kg.

Nivolumab will be administered as an i.v. infusion, using a volumetric pump with a 0.2 micron in-line filter at the protocol-specified dose(s) and rate.

Other Names:
  • BMS-936558
  • NSC 748726
  • Anti PD-1
  • antibody
  • MDX-1106
  • Immunotherapy
  • HMA
Biological: gp100:280-288 (288V)

The vaccine contains two peptides from two different proteins (peptides are pieces that make up proteins) called gpl00 and NY-ES0-1.

Route of Administration: When prepared as a vaccine emulsion with Montanide ISA 51 VG, the vaccine is given by deep subcutaneous injection.

Method of Administration: The 0.5 mg vaccine emulsion dose is administered as a 1 mL injection (0.5 mg/1 mL) as a deep subcutaneous injection in the anterior thigh of the same extremity.

Other Names:
  • NSC 683473
  • Peptide
  • g9-288-9V Peptide
Drug: Montanide ISA 51 vegetable grade (VG)

Route of Administration: Administer peptide vaccine emulsions prepared with Montanide® ISA 51 VG by deep subcutaneous injection.

Method of Administration: Divide peptide vaccine emulsion dose volumes of greater than 1.5 mL into 2 or more injections. Administer injections typically into the anterior thigh deep subcutaneous tissue. Perform subsequent injections in rotating sites. Use a 20 or 21 gauge needle for deep subcutaneous injection of the peptide vaccine emulsion.

Other Name: NSC 737063
Procedure: Apheresis Procedure
Some blood will be removed from the participant's veins and processed by a machine to remove a small portion of the white cells. The rest of the blood will be returned into their veins. This procedure is called "apheresis." Apheresis is done to collect cells to allow the investigators to understand how their immune system is functioning before and after receiving nivolumab and vaccine. This will be done for research purposes only. The red cells and blood clotting cells will not be permanently removed during this procedure. White blood cells will need to be removed by apheresis before participants receive the study drug.
Experimental: Nivolumab and Ipilimumab
Cohorts 4 and 5. Participants will receive their first dose of nivolumab with ipilimumab within 28 days after screening blood draws. Both drugs will be given. Cohort 4: nivolumab 1mg/kg plus ipilimumab 3mg/kg. Cohort 5: nivolumab 3mg/kg plus ipilimumab 1mg/kg.
Drug: Nivolumab

Nivolumab (BMS-936558) is a fully human monoclonal antibody (HuMAb) against programmed death-1 (PD-1).

Nivolumab will be given at the following dosages: 1, 3, or 10 mg/kg.

Nivolumab will be administered as an i.v. infusion, using a volumetric pump with a 0.2 micron in-line filter at the protocol-specified dose(s) and rate.

Other Names:
  • BMS-936558
  • NSC 748726
  • Anti PD-1
  • antibody
  • MDX-1106
  • Immunotherapy
  • HMA
Drug: Ipilimumab

Ipilimumab will be given at the following dosage: 3 mg/kg.

Ipilimumab will be administered as an i.v. infusion, using a volumetric pump with a 0.2 micron in-line filter at the protocol-specified dose(s) and rate.

Other Name: NSC 732442

Detailed Description:

Up to 5 dose cohorts will be studied. Participants will be assigned to a dose cohort in the order they enter the study.

  • 1 mg/kg of NIVOLUMAB + peptide vaccine (1 mg/kg cohort), then
  • 3 mg/kg of NIVOLUMAB + peptide vaccine (3 mg/kg cohort), then
  • 10 mg/kg of NIVOLUMAB + peptide vaccine (10 mg/kg cohort), then
  • 1 mg/kg NIVOLUMAB + ipilimumab 3 mg/kg combination cohort
  • 3 mg/kg NIVOLUMAB + ipilimumab 1 mg/kg combination cohort
  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologic diagnosis of resected Stages IIIC/ IV melanoma, with no evidence of disease clinically and radiologically. All melanomas regardless of primary site of disease will be allowed.
  • HLA-A*0201 positive as determined by deoxyribonucleic (DNA) allele-specific polymerase chain reaction (PCR) assay; HLA restriction is not required for cohort 4
  • Positive staining of most recently resected tumor tissue with antibodies to 1 or more of the following: human melanoma black 45 (HMB 45) for gp100, NY-ESO-1, and/or MART-1
  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
  • Prior chemotherapy or immunotherapy (tumor vaccine, cytokine, or growth factor given to control the cancer) must have been completed at least 4 weeks before study drug administration, and all adverse events have either returned to baseline or stabilized.
  • Prior treated brain or meningeal metastases must be without magnetic resonance imaging (MRI) evidence of progression for at least 8 weeks and off immunosuppressive doses of systemic steroids (> 10 mg/day prednisone or equivalent) for at least 2 weeks before study drug administration.
  • Prior systemic radiation therapy must have been completed at least 4 weeks before study drug administration. Prior focal radiotherapy completed at least 2 weeks before study drug administration. No radiopharmaceuticals (strontium, samarium) within 8 weeks before study drug administration.
  • Immunosuppressive doses of systemic medications, such as steroids or absorbed topical steroids (doses > 10 mg/day prednisone or equivalent) must be discontinued at least 2 weeks before study drug administration.
  • Completed nitrosourea treatment at least 6 weeks before administration of any study drug.
  • Prior surgery that required general anesthesia must be completed at least 4 weeks before study drug administration. Surgery requiring local/epidural anesthesia must be completed at least 72 hours before study drug administration and participants should be recovered.
  • Screening laboratory values must meet the following criteria: white blood cells (WBCs) ≥ 2000 cells/μL, neutrophils ≥ 1500 cells/μL, platelets ≥ 100 x 10^3/μL, hemoglobin ≥ 9.0 g/dL, serum creatinine ≤ 2 mg/dL, aspartic transaminase (AST) ≤ 2.5 x upper limit of normal (ULN) without, and ≤ 5 x ULN with hepatic metastasis, alanine transaminase (ALT) ≤ 2.5 x ULN without, and ≤ 5 x ULN with hepatic metastasis, bilirubin ≤ 2 x ULN (except participants with Gilbert's syndrome, who must have total bilirubin < 3.0 mg/dL).
  • Females of childbearing potential (FOCBP) must: Agree to use using a reliable form of contraception (e.g., oral contraceptives, intrauterine device, double barrier method of condom and spermicidal) for at least 28 days prior to the first dose of any study drug, during the Treatment Period (and Treatment/Follow-up if receiving study drug), and for at least 70 days after the last dose of any study drug; have a negative serum β-human chorionic gonadotropin (β-HCG) at Screening.
  • For female participants to be considered as not having childbearing potential, they must meet 1 or more of the following criteria: postmenopausal for at least 24 consecutive months; surgically sterile (ie, have had a hysterectomy or bilateral oophorectomy); females with irregular menstrual periods and/or on hormone replacement therapy must have a documented serum follicle stimulating hormone level > 35 mIU/mL.
  • Male participants must agree to the use of male contraception during the Treatment Period and for at least 180 days after the last dose of any study drug.
  • Must have read, understood, and provided written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization after the nature of the study has been fully explained.
  • Willing to adhere to the study visit schedule and the prohibitions and restrictions specified in this protocol.

Exclusion Criteria:

  • History of severe hypersensitivity reactions to other monoclonal antibodies (mAbs).
  • Systemic hypersensitivity to Montanide ISA 51 VG or any vaccine component.
  • Prior non-melanoma malignancy active within the previous 2 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix or breast.
  • Any active autoimmune disease or documented history of autoimmune disease, or history of syndrome that required systemic steroids or immunosuppressive medications, except for participants with vitiligo or resolved childhood asthma/atopy.
  • Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
  • Positive tests for hepatitis B virus surface antigen (HBV SAg) or hepatitis C virus ribonucleic acid (HCV RNA) indicating active or chronic infection.
  • Prior therapy with an anti-Programmed Death-1(anti-PD-1), anti-Programmed Death-Ligand 1 (anti-PD-L1), anti-programmed death-ligand-2 (anti-PD-L2), or anti-cytotoxic T lymphocyte-associated antigen 4 (anti-CTLA-4) antibody(or any other antibody targeting T cell co-stimulation pathways).
  • Concurrent medical condition requiring the use of immunosuppressive medications, or immunosuppressive doses of systemic or absorbable topical corticosteroids.
  • Underlying medical condition (eg, a condition associated with diarrhea) that, in the Investigator's opinion, would make the administration of either study drug or both study drugs hazardous to the participant or obscure the interpretation of toxicity determination or adverse events.
  • Pregnant or nursing.
  • Current participation in another clinical study involving treatment with medications, radiation or surgery, or prior participation in this study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01176474

Locations
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute Recruiting
Tampa, Florida, United States, 33612-9497
Contact: Allison Richards    813-745-8352    allison.richards@moffitt.org   
Principal Investigator: Jeffrey S. Weber, M.D., Ph.D.         
Sub-Investigator: Geoffrey Gibney, M.D.         
Sub-Investigator: Jonathan Zager, M.D.         
Sub-Investigator: Amod Sarnaik, M.D.         
Sub-Investigator: Shilpa Gupta, M.D.         
Sub-Investigator: Jingsong Zhang, M.D., Ph.D.         
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
Medarex
Bristol-Myers Squibb
Investigators
Principal Investigator: Jeffrey S. Weber, M.D., Ph.D. H. Lee Moffitt Cancer Center and Research Institute
  More Information

Additional Information:
No publications provided

Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT01176474     History of Changes
Other Study ID Numbers: MCC-15651, NCI-8316
Study First Received: August 5, 2010
Last Updated: August 13, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
stage IV melanoma
stage IIIC melanoma

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Antibodies
Immunoglobulins
Freund's Adjuvant
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Adjuvants, Immunologic

ClinicalTrials.gov processed this record on August 20, 2014