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

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

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.

Study Overview

• Status: Completed
• Conditions: Melanoma (Skin)
• Intervention / Treatment: 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.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095-1781
      • Jonsson Comprehensive Cancer Center at UCLA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum tolerated dose of anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody	3 months

Collaborators and Investigators

• Sponsor: Jonsson Comprehensive Cancer Center
• Collaborators: Pfizer
• Investigators: Study Chair: Antoni Ribas, MD, Jonsson Comprehensive Cancer Center

Publications and helpful links

General Publications

• Comin-Anduix B, Sazegar H, Chodon T, Matsunaga D, Jalil J, von Euw E, Escuin-Ordinas H, Balderas R, Chmielowski B, Gomez-Navarro J, Koya RC, Ribas A. Modulation of cell signaling networks after CTLA4 blockade in patients with metastatic melanoma. PLoS One. 2010 Sep 15;5(9):e12711. doi: 10.1371/journal.pone.0012711.

Study record dates

Study Major Dates

• Study Start: April 1, 2004
• Primary Completion (Actual): July 1, 2008
• Study Completion (Actual): October 1, 2009

Study Registration Dates

• First Submitted: September 7, 2004
• First Submitted That Met QC Criteria: September 7, 2004
• First Posted (Estimate): September 8, 2004

Study Record Updates

• Last Update Posted (Actual): August 3, 2020
• Last Update Submitted That Met QC Criteria: July 30, 2020
• Last Verified: August 1, 2012

More Information

Terms related to this study

• Keywords: recurrent melanoma; stage IV melanoma; stage III melanoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antibodies; Antibodies, Monoclonal; Ipilimumab
• Other Study ID Numbers: CDR0000380840; UCLA-0312023; PFIZER-NRA3670003