Recurrent MelanomaPhase 1NCT01103635
Tremelimumab and CP-870,893 in Patients With Metastatic Melanoma
A Phase 1 study testing CD40 agonist monoclonal antibody CP-870,893, tremelimumab and laboratory biomarker analysis in people with Recurrent Melanoma and Stage IV Melanoma, run by Abramson Cancer Center at Penn Medicine at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Recurrent Melanoma, Stage IV Melanoma
- What is being tested?
- CD40 agonist monoclonal antibody CP-870,893, tremelimumab and laboratory biomarker analysis
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2010to 2 May 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with metastatic melanoma who have measurable disease
- ECOG PS 0 or 1
- Adequate bone marrow function
- WBC >= 3,000
- Hgb >= 9
- Plt >= 100
Show all 10Show fewer
- 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
Who cannot join
- 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
Show all 17Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Abramson Cancer Center of The University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
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
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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.
- Conditions
- Recurrent Melanoma, Stage IV Melanoma
- Being tested
- CD40 agonist monoclonal antibody CP-870,893, tremelimumab, laboratory biomarker analysis
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CD40 agonist monoclonal antibody CP-870,893Biological
Also called CP-870,893
Given IV
tremelimumabBiological
Also called anti-CTLA4 human monoclonal antibody CP-675,206, CP-675,206
Given IV
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Biological: CD40 agonist monoclonal antibody CP-870,893; Biological: tremelimumab; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Apr 2010 (estimated)
- Study startFeb 2010
- Primary completionMay 2016
- Study completion2 May 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Recurrent MelanomaStudies of the same condition, open and under way.
- More trials run by Abramson Cancer Center at Penn MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Abramson Cancer Center at Penn Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Robert Vonderheide, MD, DPhil, Principal investigator, Abramson Cancer Center at Penn Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01103635
- Sponsor's protocol ID
- UPCC 05609
- Other IDs
- NCI-2010-00507
- Status last verified
- Apr 2020
- First submitted
- 12 Apr 2010
- Last updated
- 7 Apr 2020
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 7 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01103635
- Acronym / sponsor ID
- UPCC 05609
- Conditions
- Recurrent Melanoma, Stage IV Melanoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Abramson Cancer Center at Penn MedicineUniversity, hospital or other
- Study start
- Feb 2010 (actual)
- Primary completion
- May 2016 (actual)
- Study completion
- 2 May 2016 (actual)
- First posted
- 14 Apr 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm I | Experimental | Biological: CD40 agonist monoclonal antibody CP-870,893, Biological: tremelimumab, Other: laboratory biomarker analysisPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Patients with metastatic melanoma who have measurable disease
- ECOG PS 0 or 1
- Adequate bone marrow function
- WBC >= 3,000
- Hgb >= 9
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CD40 agonist monoclonal antibody CP-870,893Also: CP-870,893Given IV | Biological | Arm I |
| tremelimumabAlso: anti-CTLA4 human monoclonal antibody CP-675,206, CP-675,206Given IV | Biological | Arm I |
| laboratory biomarker analysisCorrelative studies | Other | Arm I |
Primary outcome
Toxicity as assessed by CTCAE v3.0
Time frame: 2 years
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
Time frame: 2 years
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)
Time frame: 2 years
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.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Apr 2020.
Related trials for Recurrent Melanoma
RecruitingPhase 2
BiCaZO: A Study Combining Two Immunotherapies (Cabozantinib and Nivolumab) to Treat Patients With Advanced Melanoma or Squamous Cell Head and Neck Cancer, an immunoMATCH Pilot Study
Clinical Stage III Cutaneous Melanoma AJCC v8, Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8
Not yet recruitingPhase 2
A Study Comparing Cemiplimab-based Treatments for Adult Participants With Locally Advanced Basal Cell Skin Cancer (laBCC)
Locally Advanced Basal Cell Carcinoma
RecruitingPhase 1
A Phase 1 Study to Evaluate OPB-201 in Recurrent Endometrial and Platinum-resistant Ovarian Cancer.
Endometrial Cancer Recurrent, Endometrial Cancer
RecruitingPhase 1/2
A Study to Evaluate the Efficacy and Safety of Ifinatamab Deruxtecan (I-DXd) in Subjects With Recurrent or Metastatic Solid Tumors (IDeate-PanTumor02)
Recurrent or Metastatic Solid Tumors
Active, not recruitingPhase 2
Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)
Advanced Lymphoma, Advanced Malignant Solid Neoplasm
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert Vonderheide, MD, DPhil principal investigator
Abramson Cancer Center at Penn Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CD40 agonist monoclonal antibody CP-870,893, tremelimumab and laboratory biomarker analysis in people with Recurrent Melanoma and Stage IV Melanoma, run by Abramson Cancer Center at Penn Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Toxicity as assessed by CTCAE v3.0 (time frame: 2 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Apr 2020; AzTrials last refreshed its copy on 8 Nov 2026.