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
- Conditions
- Melanoma (Skin)
- Interventions
- Biological: maximum tolerated dose of anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody
- Registration Number
- NCT00090896
- Lead Sponsor
- Jonsson Comprehensive Cancer Center
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 18
-
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)
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description CTLA4-Blocking Monoclonal Antibody maximum tolerated dose of anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody -
- Primary Outcome Measures
Name Time Method Maximum tolerated dose of anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody 3 months
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
Jonsson Comprehensive Cancer Center at UCLA
🇺🇸Los Angeles, California, United States