CP-675,206 In Patients With Advanced Melanoma

Sponsor

AstraZeneca (Industry)

Overall Status

Completed

CT.gov ID

NCT00086489

Collaborator

(none)

118

Enrollment

Locations

Arms

Duration (Months)

13.1

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the efficacy, safety, and tolerability of monoclonal antibody therapy using 2 regimens for the treatment of advanced melanoma

Condition or Disease	Intervention/Treatment	Phase
Malignant Melanoma	Drug: CP-675,206 Drug: CP-675,206	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

118 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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.

Study Start Date :

Aug 1, 2003

Actual Primary Completion Date :

May 1, 2007

Actual Study Completion Date :

May 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 10 mg/kg pts treated at 10 mg/kg dose level on a monthly regimen	Drug: CP-675,206 pts treated at 10 mg/kg dose level on a monthly regimen
Experimental: 15 mg/kg pts treated at 15 mg/kg dose level on a quarterly regimen	Drug: CP-675,206 pts treated at 15 mg/kg dose level on a quarterly regimen

Arm

Intervention/Treatment

Experimental: 10 mg/kg

pts treated at 10 mg/kg dose level on a monthly regimen

Drug: CP-675,206

pts treated at 10 mg/kg dose level on a monthly regimen

Experimental: 15 mg/kg

pts treated at 15 mg/kg dose level on a quarterly regimen

Drug: CP-675,206

pts treated at 15 mg/kg dose level on a quarterly regimen

Outcome Measures

Primary Outcome Measures

Safety [At every scheduled visit for a maximum of 2 years from first dose of study drug]
Tumor response [Assessed every 2-3 months up to 2 years from first dose of study drug]

Secondary Outcome Measures

Monitor for human anti-human antibodies at the end of the study [Pre-dose (Cycle 1 only) and end of study]
Explore genetic influences on safety and or immune response [Pre-dose, Cycle 1]
Assess PK during treatment [All cycles as pre-specified in protocol]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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 for exclusion.
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.

Exclusion Criteria:

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 protocol.
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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Los Angeles	California	United States	90095
2	Research Site	Tampa	Florida	United States	33612
3	Research Site	Chicago	Illinois	United States	60637-1460
4	Research Site	Ann Arbor	Michigan	United States	48109-0008
5	Research Site	Ann Arbor	Michigan	United States	48109-0843
6	Research Site	Pittsburgh	Pennsylvania	United States	15232-1305
7	Research Site	Pittsburgh	Pennsylvania	United States	15232
8	Research Site	Nashville	Tennessee	United States	37232
9	Research Site	Houston	Texas	United States	77030