Tremelimumab and CP-870,893 in Patients With Metastatic Melanoma

NCT01103635 | Completed Phase 1 DMC

• 2 other identifiers: UPCC 05609NCI-2010-00507
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Recurrent Melanoma; Stage IV Melanoma

Outcome Measures

Primary Outcomes (3)

• Toxicity as assessed by CTCAE v3.0

  Toxicities which occur during later cycles will be monitored and described separately. The MTD is defined as the dose level at which 0-1/6 patients experience DLT in the first 12 week cycle and at least 2/3 or 2/6 patients treated at the next higher dose level (unless MTD is level 4) experience DLT in the first 12 week cycle.

  2 years

• Response

  Clinical response will be scored using RECIST criteria. Patients who do not complete a clinical response evaluation will be scored as unevaluable. The objective response rate is defined as the proportion of patients treated at the MTD who achieve either a complete or partial response. Unevaluable patients are included in the calculation of the objective response rate.

  2 years

• Immunological outcomes (analysis of antigen presenting cell activation, antigen-specific T cells, and tumor-specific T cells)

  Analysis of antigen presenting cell (APC) activation, 2) analysis of antigen-specific T cells and 3) tumor-specific T cells, as described in Section 7.2. For T cell response analyses, overall immune response is defined as \>2 fold pre-treatment/post-treatment increase in any of the key T cell parameters.

  2 years

Study Arms (1)

Arm I

EXPERIMENTAL

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.

Biological: CD40 agonist monoclonal antibody CP-870,893; Biological: tremelimumab; Other: laboratory biomarker analysis

Interventions

CD40 agonist monoclonal antibody CP-870,893 BIOLOGICAL

Given IV

Also known as: CP-870,893

Arm I

tremelimumab BIOLOGICAL

Given IV

Also known as: anti-CTLA4 human monoclonal antibody CP-675,206, CP-675,206

Arm I

laboratory biomarker analysis OTHER

Correlative studies

Arm I

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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 (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

Sponsors & Collaborators

• Abramson Cancer Center at Penn Medicine: lead

Study Sites (1)

Abramson Cancer Center of The University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

selicrelumab; tremelimumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Robert Vonderheide, MD, DPhil

  Abramson Cancer Center at Penn Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 12, 2010
• First Posted: April 14, 2010
• Study Start: February 1, 2010
• Primary Completion: May 1, 2016
• Study Completion: May 2, 2016
• Last Updated: April 7, 2020

Record last verified: 2020-04

Locations

US (1)