CP-675,206 (CTLA4-Blocking Monoclonal Antibody) Combined With Dendritic Cell Vaccine Therapy in Treating Patients With Stage III or Stage IV Melanoma That Cannot Be Removed With Surgery

Sponsor

Jonsson Comprehensive Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT00090896

Collaborator

Pfizer (Industry)

Enrollment

Location

Arm

Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Biological therapies, such as CP-675,206, work in different ways to stimulate the immune system and stop tumor cells from growing. Vaccines may make the body build an immune response to kill tumor cells. Combining CP-675,206 with vaccine therapy may cause a stronger immune response and kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of CP-675,206 when given with vaccine therapy in treating patients with stage III or stage IV melanoma that cannot be removed with surgery.

Condition or Disease	Intervention/Treatment	Phase
Melanoma (Skin)	Biological: maximum tolerated dose of anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody	Phase 1

Detailed Description

OBJECTIVES:

Primary

Determine the safety and maximum tolerated dose of anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (CTLA4-blocking monoclonal antibody; CP-675,206) administered with autologous dendritic cells pulsed with MART-1 antigen in patients with unresectable stage III or stage IV melanoma.
Determine the biological activity and immune effects of this regimen in these patients.

Secondary

Correlate CTLA4 genotype with safety of this regimen and/or immune response in these patients.
Determine, preliminarily, the efficacy of this regimen, in terms of clinical benefit rate, in these patients.

OUTLINE: This is an open-label, dose-escalation study of anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (CTLA4-blocking monoclonal antibody; CP-675,206).

Patients receive CP-675,206 IV on days 0, 28, 60, and 90 and autologous dendritic cells pulsed with MART-1 antigen intradermally on days 0, 14, and 28. After day 120, patients with stable or responding disease may receive additional doses of CP-675,206 monthly in the absence of disease progression or unacceptable toxicity

Cohorts of 3-6 patients receive escalating doses of CP-675,206 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed every 3 months.

PROJECTED ACCRUAL: A total of 3-21 patients will be accrued for this study within 3-10 months.

Study Design

Study Type:

Interventional

Actual Enrollment :

18 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I, Open Label, Study To Evaluate The Safety And Immune Function Effects Of CP-675,206 In Combination With MART-1 Peptide-Pulsed Dendritic Cells In Patients With Advanced Melanoma

Study Start Date :

Apr 1, 2004

Actual Primary Completion Date :

Jul 1, 2008

Actual Study Completion Date :

Oct 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CTLA4-Blocking Monoclonal Antibody	Biological: maximum tolerated dose of anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody

Arm

Intervention/Treatment

Experimental: CTLA4-Blocking Monoclonal Antibody

Biological: maximum tolerated dose of anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody

Outcome Measures

Primary Outcome Measures

Maximum tolerated dose of anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody [3 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologically confirmed cutaneous or mucosal melanoma, meeting criteria for 1 of the following:
Unresectable stage III disease (locally relapsed unresectable, in-transit lesions, or unresectable draining nodes)
Stage IV disease, metastatic to 1 of the following sites:
Skin, subcutaneous tissues, or distant lymph nodes
Lung
Other visceral sites with lactic dehydrogenase ≤ 2 times upper limit of normal (unless due to liver stasis)
De novo metastatic disease allowed provided patient refused any standard or approved stage-appropriate therapy for melanoma
Measurable disease
HLA-A2.1 positive (HLA-A*0201 by molecular subtyping)
MART-1-expressing tumor by reverse transcription polymerase chain reaction or immunohistochemistry
No symptomatic brain metastases and/or progression of CNS metastases within the past 4 weeks
Age 18 and over
Performance status ECOG 0-1 OR
Karnofsky 70-100%
HIV negative
Negative pregnancy test
Fertile patients must use effective barrier contraception during and for 3 months after study participation
More than 30 days since prior immunotherapy for metastatic, relapsed, or primary melanoma
More than 30 days since prior chemotherapy for metastatic, relapsed, or primary melanoma
More than 4 weeks since prior corticosteroids
More than 30 days since prior radiotherapy for metastatic, relapsed, or primary melanoma
More than 30 days since prior surgery for metastatic, relapsed, or primary melanoma.
More than 30 days since other prior therapy for metastatic, relapsed, or primary melanoma
More than 14 days since prior anti-infective therapy
More than 4 weeks since prior immune suppressive therapy (e.g., cyclosporine)

Exclusion Criteria:

chronic hepatitis B or C
asthma
inflammatory bowel disease
celiac disease
history of chronic colitis or other chronic gastrointestinal conditions associated with diarrhea or bleeding
active chronic inflammatory or autoimmune disease, including any of the following:
Psoriasis
Rheumatoid arthritis
Multiple sclerosis
Hashimoto's thyroiditis
Addison's disease
Graves' disease
Systemic lupus erythematosus
active infection OR fever over 100° F within the past 3 days
allergy to study drugs
pregnant
symptomatic seizures
other medical problem that would preclude study participation
prior melanoma immunotherapy containing MART-1 antigen
prior anti-T-cell therapy
prior anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (CP-675,206)
organ allografts requiring long-term immune suppressive therapy