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A Pilot Trial of a Vaccine Combining Multiple Class I Peptides and Montanide ISA 51 VG With Escalating Doses of Anti-PD-1 Antibody BMS-936558 for Patients With Unresectable Stages III/IV Melanoma


Phase 1
16 Years
N/A
Open (Enrolling)
Both
Melanoma (Skin)

Thank you

Trial Information

A Pilot Trial of a Vaccine Combining Multiple Class I Peptides and Montanide ISA 51 VG With Escalating Doses of Anti-PD-1 Antibody BMS-936558 for Patients With Unresectable Stages III/IV Melanoma


BMS-936558 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.

The vaccine consists of the following peptides: gp100280-288 (288V), and NY-ESO-1157-165
(165V).

NOTE: *Patients in cohorts 1-5 will receive the peptide vaccine, but not those in cohort 6.

Blood samples are collected for pharmacokinetic and immunologic analysis.

After completion of study therapy, patients are followed up periodically for 2 years.


Inclusion Criteria:



- Histologic diagnosis of unresectable Stage III or IV melanoma. All melanomas
regardless of primary site of disease will be allowed

- Measurable unresectable melanoma at least 1 measurable lesion based on Immune-related
Response Criteria (irRC)

- Have failed at least 1 chemotherapy regimen for metastatic disease, and have been
treated with up to 2 prior chemotherapy regimens

- HLA-A*0201 positive as determined by deoxyribonucleic (DNA) allele-specific
polymerase chain reaction (PCR) assay; for cohort 5 after amendment 9 and cohort 6,
there is no HLA restriction

- Positive staining of 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 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 2 weeks
before study drug administration. Surgery requiring local/epidural anesthesia must be
completed at least 72 hours before study drug administration and patients 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 patients with Gilbert's syndrome, who must have
total bilirubin < 3.0 mg/dL)

- Females of childbearing potential must: Agree to use using a reliable form of
contraception (eg, 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.

- Males 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 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

- Patients with any active autoimmune disease or a documented history of autoimmune
disease, or history of syndrome that required systemic steroids or immunosuppressive
medications, except for patients 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-PD-1, anti-PD-L1, anti-programmed death-ligand-2 (PDL-2),
or anti-cytotoxic T lymphocyte-associated antigen 4 (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 patient 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

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Best Overall Response Rate (BORR)

Outcome Description:

The primary analysis is the BORR as determined using irRC. The BORR will be summarized using descriptive statistics.

Outcome Time Frame:

2 years, 6 months

Safety Issue:

No

Principal Investigator

Jeffrey S. Weber, M.D., Ph.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

H. Lee Moffitt Cancer Center and Research Institute

Authority:

United States: Food and Drug Administration

Study ID:

MCC-15400

NCT ID:

NCT01176461

Start Date:

August 2010

Completion Date:

June 2014

Related Keywords:

  • Melanoma (Skin)
  • recurrent melanoma
  • stage IIIA melanoma
  • stage IIIB melanoma
  • stage IIIC melanoma
  • stage IV melanoma
  • Melanoma

Name

Location

H. Lee Moffitt Cancer Center and Research InstituteTampa, Florida  33612