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

Primary Purpose

Recurrent Melanoma, Stage IV Melanoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
CD40 agonist monoclonal antibody CP-870,893
tremelimumab
laboratory biomarker analysis
Sponsored by
Abramson Cancer Center at Penn Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Melanoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Abramson Cancer Center of The University of Pennsylvania

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm I

Arm Description

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.

Outcomes

Primary Outcome Measures

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.
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.
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.

Secondary Outcome Measures

Full Information

First Posted
April 12, 2010
Last Updated
April 6, 2020
Sponsor
Abramson Cancer Center at Penn Medicine
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1. Study Identification

Unique Protocol Identification Number
NCT01103635
Brief Title
Tremelimumab and CP-870,893 in Patients With Metastatic Melanoma
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2020
Overall Recruitment Status
Completed
Study Start Date
February 2010 (Actual)
Primary Completion Date
May 2016 (Actual)
Study Completion Date
May 2, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Abramson Cancer Center at Penn Medicine

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Melanoma, Stage IV Melanoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm I
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
CD40 agonist monoclonal antibody CP-870,893
Other Intervention Name(s)
CP-870,893
Intervention Description
Given IV
Intervention Type
Biological
Intervention Name(s)
tremelimumab
Other Intervention Name(s)
anti-CTLA4 human monoclonal antibody CP-675,206, CP-675,206
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Toxicity as assessed by CTCAE v3.0
Description
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.
Time Frame
2 years
Title
Response
Description
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.
Time Frame
2 years
Title
Immunological outcomes (analysis of antigen presenting cell activation, antigen-specific T cells, and tumor-specific T cells)
Description
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.
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert Vonderheide, MD, DPhil
Organizational Affiliation
Abramson Cancer Center at Penn Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Abramson Cancer Center of The University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States

12. IPD Sharing Statement

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

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