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

Melanoma (Skin) Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00090896
• Other study ID #: CDR0000380840
• Secondary ID: UCLA-0312023PFIZ
• Status: Completed
• Phase: Phase 1
• Start date: April 2004
• Est. completion date: October 2009

Study information

• Verified date: August 2012
• Source: Jonsson Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: October 2009
• Est. primary completion date: July 2008
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

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

Related Conditions & MeSH terms

• Melanoma
• Melanoma (Skin)

Intervention

Biological:
• maximum tolerated dose of anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody

Locations

Country	Name	City	State
United States	Jonsson Comprehensive Cancer Center at UCLA	Los Angeles	California

Sponsors (2)

Lead Sponsor	Collaborator
Jonsson Comprehensive Cancer Center	Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum tolerated dose of anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody		3 months