Phase 1 Open Label, Non-Randomized, Dose Escalation Study To Evaluate The Safety, Tolerability, Pharmacokinetics, Immune Function Effects, And Efficacy Of Multiple Doses Of CP-675,206 In Patients With Advanced Melanoma, And Phase 2, Open Label, Randomized Study To Evaluate the Efficacy, Safety, Tolerability And Pharmacokinetics Of 2 Regimens Of CP-675,206 In Patients With Advanced Melanoma.
- Histologically confirmed: Stage III (AJCC 6th edition)xxl unresectable melanoma, with
measurable disease (either locally relapsed unresectable, in-transit lesions or
unresectable draining nodes) or Stage IV melanoma, including:
- Metastasis to skin, subcutaneous tissues or distant lymph nodes, or
- Metastasis to lungs, or
- Metastasis to all other visceral sites with either LDH <= ULN (upper limit of normal)
or a single site of metastasis
- Note: Patients with melanoma of ocular origin will be considered ineligible
- Documented progressive disease following adjuvant therapy, localized therapy or other
therapy for metastatic disease
- Measurable disease defined by at least one target lesion that can be accurately
measured and whose size is at least 1.0 cm (by spiral CT) or 2.0 cm (by conventional
techniques) in its longest diameter
- ECOG performance status of 0 or 1 Life expectancy of > 3 months
- Either gender, aged 18 years and above
- Adequate bone marrow, hepatic, and renal functions determined within 2 weeks prior to
starting therapy, defined as:
- Absolute neutrophil count >= 1.5 x 10(9)cells/L
- Platelets >= 100 x 10(9)/L
- Hemoglobin >= 10 g/dL
- Aspartate and alanine aminotransferases (AST, ALT) <= 2.5 x ULN (<= 5 x ULN, if
documented liver metastases are present)
- Total bilirubin <= 1.5 x ULN
- Creatinine <= 1.5 x ULN
- Patients must have recovered from all prior treatment related toxicities, to baseline
status, or a CTC grade of 0 or 1. Post-surgical pain shall not be considered a basis
- Females must either be not of childbearing potential [surgically sterilized, which
includes tubal ligation, or at least 2 years postmenopausal; not breastfeeding], or
practicing 1 form of approved contraception for at least three months prior to entry
into the study with 1 of the following methods: (a) oral contraceptives, (b)
intrauterine device, (c) implanted contraceptive (such as Norplant®), (d) injected
contraceptives (such as Depo-Provera®), (e) diaphragm, (f) sexual partner must use
condom or be surgically sterilized, or (g) sexually inactive. Females of childbearing
potential must be instructed to avoid pregnancy during study participation. Negative
serum or urine pregnancy test must be documented during screening evaluation.
- Must be willing and able to provide written informed consent.
- Received immunotherapy for cancer within one month prior to the start of screening
- Patients previously treated on this protocol
- History of, or significant evidence of risk for, chronic inflammatory or autoimmune
disease (e.g. Addison's disease, asthma, celiac disease, multiple sclerosis, Graves
Disease, Hashimoto's thyroiditis, inflammatory bowel disease, psoriasis, rheumatoid
arthritis, systemic lupus erythematosus, etc.)
- Potential requirement for systemic corticosteroids or concurrent immunosuppressive
drugs based on prior history.
- History of autoimmune colitis or other chronic gastrointestinal conditions associated
with diarrhea or bleeding, or current acute colitis of any origin.
- Pregnant or lactating women.
- Dementia or significantly altered mental status that would prohibit the understanding
or rendering of informed consent and compliance with the requirements of this
- Diagnosed or suspected brain metastases. Patients with past history of brain
metastases but with no radiologic evidence within 12 weeks prior to enter into the
protocol will be eligible.
- Any serious uncontrolled medical disorder or active infection, which would impair
their ability to receive study treatment.
- Coexisting malignancies except for basal or squamous cell carcinoma of the skin.
- Received any prior CTLA4 inhibiting agent