Melanoma (Skin)
Conditions
Keywords
recurrent melanoma, stage III melanoma, stage IV melanoma
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.
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.
Interventions
BIOLOGICALmaximum tolerated dose of anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody
Sponsors
Pfizer
Jonsson Comprehensive Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum tolerated dose of anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody | 3 months |
Countries
United States
Outcome results
None listed