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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Jonsson Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00090896
First received: September 7, 2004
Last updated: August 2, 2012
Last verified: August 2012
  Purpose

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

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Jonsson Comprehensive Cancer Center:

Primary Outcome Measures:
  • Maximum tolerated dose of anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]

Enrollment: 18
Study Start Date: April 2004
Study Completion Date: October 2009
Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CTLA4-Blocking Monoclonal Antibody Biological: maximum tolerated dose of anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00090896

Locations
United States, California
Jonsson Comprehensive Cancer Center at UCLA
Los Angeles, California, United States, 90095-1781
Sponsors and Collaborators
Jonsson Comprehensive Cancer Center
Investigators
Study Chair: Antoni Ribas, MD Jonsson Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided by Jonsson Comprehensive Cancer Center

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Jonsson Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00090896     History of Changes
Other Study ID Numbers: CDR0000380840, P30CA016042, UCLA-0312023, PFIZER-NRA3670003
Study First Received: September 7, 2004
Last Updated: August 2, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Jonsson Comprehensive Cancer Center:
recurrent melanoma
stage III melanoma
stage IV melanoma

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 22, 2014