Patient case: 47-year-old male with melanoma; genetic feature: APC loss of function

Clinical trial: 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

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.

Eligibility: 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

Relevance to patient case: not relevant