This trial is active, not recruiting.

Conditions recurrent melanoma, stage iv melanoma
Treatments cd40 agonist monoclonal antibody cp-870,893, tremelimumab, laboratory biomarker analysis
Phase phase 1
Target CTLA-4
Sponsor Abramson Cancer Center of the University of Pennsylvania
Start date February 2010
End date October 2014
Trial size 32 participants
Trial identifier NCT01103635, NCI-2010-00507, UPCC 05609


RATIONALE: Monoclonal antibodies, such as tremelimumab and CD40 agonist monoclonal antibody CP-870,893, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry cancer-killing substances to them. Giving tremelimumab together with CD 40 agonist monoclonal antibody CP-870, 893 may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of giving tremelimumab together with CD40 agonist monoclonal antibody CP-870,893 in treating patients with metastatic melanoma.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Patients receive tremelimumab over 1 hour on day 1 and CD40 agonist monoclonal antibody CP-870,893 IV over 30 minutes on days 2, 22, 43, and 64. Treatment repeats every 12 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
cd40 agonist monoclonal antibody cp-870,893 CP-870,893
Given IV
tremelimumab anti-CTLA4 human monoclonal antibody CP-675,206
Given IV
laboratory biomarker analysis
Correlative studies

Primary Outcomes

Toxicity as assessed by CTCAE v3.0
time frame:
time frame:
Immunological outcomes (analysis of antigen presenting cell activation, antigen-specific T cells, and tumor-specific T cells)
time frame:

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion - Patients with metastatic melanoma who have measurable disease - ECOG PS 0 or 1 - Adequate bone marrow function - WBC >= 3,000 - Hgb >= 9 - Plt >= 100 - Adequate hepatic function, defined by the following parameters: - Total bilirubin WNL unless associated with hepatobiliary metastases or Gilbert syndrome, then total bilirubin =< 2 x ULN - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN unless associated with hepatic metastases, then ALT and AST =< 5 x ULN - Signed, written informed consent Exclusion - Previous treatment with any other compound that targets CD40 or CTLA4 - Concurrent treatment with any anticancer agent outside of this protocol - Prior allogeneic bone marrow transplant - History of brain metastases, even if previously treated - History of autoimmune disorder, including type 1 diabetes mellitus, pemphigus vulgaris, systemic mastocytosis, systemic lupus erythromatosis, dermatomyositis/polymyositis, rheumatoid arthritis, systemic sclerosis, Sjorgen's syndrome, vasculitis/arteritis, Behcet's syndrome, autoimmune thyroiditis, multiple sclerosis, or uveitis - History of chronic inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis), celiac disease, or other chronic gastrointestinal conditions associated with diarrhea, or current acute colitis or enterocolitis of any etiology - History of diverticulitis (even a single episode) or evidence at baseline, including evidence limited to CT scan only. Note diverticulosis is not an exclusion criterion per se. - History (within the previous year) of stroke or transient ischemic attack, unstable angina, myocardial infarction, congestive heart failure - History of deep venous thrombosis or migratory thrombophlebitis (Trousseau) - Hereditary or acquired coagulopathies (e.g., hemophilia, von Willebrand's disease, or cancer-associated DIC) - Prior allergic reactions attributed to other monoclonal antibodies - Concurrent or planned concurrent treatment with systemic high dose (immunosuppressive) corticosteroids or treatment with systemic corticosteroids within 4 weeks of baseline - Treatment on another therapeutic clinical trial within 4 weeks of enrollment in this trial - Concurrent or planned concurrent treatment with anticoagulants such as Coumadin or heparin, except to maintain patency of in-dwelling catheters - Ongoing or active infection; treatment with systemic antibiotics or antifungals for ongoing or recurrent infection (topical use of antibiotics or antifungals is allowed) - Pregnancy or breast-feeding; female patients must be surgically sterile, be postmenopausal, or must agree to use effective contraception during the period of therapy and for 12 months following the last dose of either tremelimumab or CP-870,893; all female patients with reproductive potential must have a negative pregnancy test prior to enrollment - Other uncontrolled, concurrent illness that would preclude study participation; or, psychiatric illness or social challenges that would entail unreasonable risk or preclude informed consent or compliance with study procedures

Additional Information

Official title A Phase 1 Dose-Escalation Trial To Evaluate Safety, Tolerability And Immune Pharmacodynamics Of Combined Administration Of Tremelimumab (Blocking Anti-CTLA-4 Antibody) And CP-870,893 (Agonist Anti-CD40 Antibody) In Patients With Metastatic Melanoma
Principal investigator Robert Vonderheide, MD, DPhil
Description PRIMARY OBJECTIVES: I. To assess the safety, dose-limiting toxicities and maximum tolerated doses of tremelimumab (administered intravenously every 12 weeks) and CP- 870,893 (administered intravenously every 3 weeks). SECONDARY OBJECTIVES: I To seek preliminary evidence of anti-tumor efficacy of the combination of tremelimumab and CP-870,893, including objective response rate at MTD. II. To determine the immune pharmacodynamic changes associated with the administration of the combination of tremelimumab and CP-870,893. OUTLINE: Patients receive tremelimumab IV over 1 hour on day 1 and CD40 agonist monoclonal antibody CP-870,893 IV over 30 minutes on days 2, 22, 43, and 64. Treatment repeats every 12 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed for 4 weeks.
Trial information was received from ClinicalTrials.gov and was last updated in July 2016.
Information provided to ClinicalTrials.gov by Abramson Cancer Center of the University of Pennsylvania.