A Phase I Study of Poly IC:LC and NY-ESO-1/gp100 Peptides Either Emulsified With Montanide ISA 51 or in Aqueous Solution With Escalating Doses of CP 870,893 in the Treatment of Subjects With Resected Stage III or Stage IV Melanoma
Patients must meet the following criteria on pre-study examination (within 28 days prior
to study drug administration) to be eligible to participate in the study:
- 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
- Histologic diagnosis of Stage III (with ≥ 3 positive lymph nodes) or Stage IV
melanoma that has been resected completely (may include mucosal or ocular melanoma)
no more than 6 months prior to screening
- Human leukocyte antigen (HLA)-A*0201 status as determined by deoxyribonucleic acid
(DNA) allele-specific polymerase chain reaction (PCR) assay
- Positive staining of tumor tissue with at least one of the following: antibody HMB-45
for gplOO, NY-ESO-l, or MART-I
- At least 4 weeks since treatment (surgery, chemotherapy, immunotherapy, radiotherapy)
and at least 6 weeks for treatment with nitrosoureas for melanoma, and at least 8
weeks since adjuvant treatment with an anti-cytotoxic T-lymphocyte-associated
antigen-4 (CTLA-4) antibody for melanoma and recovered from any serious toxicity
experienced during treatment
- Women must be either: post-menopausal for at least 1 year; surgically incapable of
bearing children; or utilizing a reliable form of contraception during the study and
for at least 4 months after the final CP 870,893 infusion or vaccination. Women of
childbearing potential must have a negative serum hCG- ß pregnancy test conducted
during the screening period and have a negative urine pregnancy test conducted on the
day of each infusion (prior to the infusion).
- Men who may father a child must agree to the use of male contraception for the
duration of their participation in the trial and for at least 4 months after the
final CP 870,893 infusion or vaccination.
- Patients with Stage III resected melanoma rendered free of disease can have failed
treatment with, been ineligible for, or refused treatment with a-interferon.
- Analgesic therapy must be stable for a period of 14 days prior to infusion of study
- Life expectancy ≥ 6 months
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Patients with resected brain metastases that are off steroids, have no evidence of
disease by brain magnetic resonance imaging (MRI) scanning, or computer tomography
(CT) of the brain if an MRI cannot be performed, are eligible.
- Screening laboratory values must meet the following criteria: white blood cell (WBC):
≥2500 cells/mm³; absolute neutrophil count (ANC): ≥1500 cells/mm³, Platelets:
≥100,000/mm³; Hematocrit: ≥30%; Hemoglobin: ≥10 g/dL; Creatinine: ≤2.0 mg/dL;
aspartate aminotransferase (AST): ≤3 x ULN; Bilirubin: ≤1.0 x upper limit of normal
(ULN) (except patients with Gilbert's Syndrome who must have a total bilirubin less
than 3.0 mg/dL); human immunodeficiency virus (HIV): negative; HBsAg: negative;
hepatitis C virus antibody (anti-HCV Ab): nonreactive. If reactive, patient must have
a negative HCV RNA qualitative PCR.
- Any prior malignancy except for the following: adequately treated basal or squamous
cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix, or any
other cancer from which the patient has been disease-free for at least 5 years.
- History of any autoimmune disease, specifically including the following diseases:
inflammatory bowel disease or any other autoimmune bowel diseases; systemic lupus
erythematosis; rheumatoid arthritis; or any autoimmune ocular diseases. Patients with
an autoimmune disease history affecting the pancreas, pituitary, liver,
gastrointestinal (GI) tract or adrenals, and prior history of Guillan-Barre and other
neurologic conditions felt to be autoimmune in nature are also excluded.
- Active infection, requiring therapy, chronic active hepatitis B virus (HBV) or HCV,
or confirmed reactivity with HIV tests.
- Pregnancy or nursing: due to the possibility that CP 870,893 could have a detrimental
effect on the developing immune system of the fetus or infant, exposure in utero or
via breast milk will not be allowed.
- Systemic hypersensitivity to Montanide ISA 51 (IFA), Montanide ISA 51 VG or any
- Any underlying medical condition which, in the opinion of the Principal Investigator
(PI), will make the administration of study drug hazardous or obscure the
interpretation of adverse events.
- Any concurrent medical condition requiring the use of systemic, inhaled or topical
corticosteroids or the use of immunosuppressive agents (e.g. cyclosporine and its
analog, or chemotherapy agents). All corticosteroid use must have been discontinued
at least 4 weeks prior to study entry.
- Prior treatment with CP 870,893 or any anti-CD40 antibody
- Evidence or history of significant cardiac, pulmonary, hepatic, renal, psychiatric or
gastrointestinal disease that would make the administration of CP 870,893 unsafe
- Concurrent treatment with chemotherapy or other immunotherapy regimens (must be
completed at least 4 weeks before Screening; 6 weeks for nitrosoureas); prior
treatment with chemotherapy, radiotherapy or other than anti CD40 antibodies will not
be an exclusion.
- History of prior allogeneic human stem cell or bone marrow transplant
- History of prior thromboembolic venous events, or inherited / acquired coagulopathies