Study of Radiotherapy Administered in Combination With Ipilimumab in Patients With Unresectable Stage III or Stage IV Advanced Malignant Melanoma (Mel-Ipi-Rx)

June 8, 2016 updated by: Gustave Roussy, Cancer Campus, Grand Paris

A Dose Escalation Phase I Study of Radiotherapy Administered in Combination With Anti-CTLA4 Monoclonal Antibody (Ipilimumab) in Patients With Unresectable Stage III or Stage IV Advanced Malignant Melanoma

RATIONALE:Anti-melanoma activity of Ipilimumab both as a single therapy and in association with melanoma peptides has been shown as well as synergy between radiation therapy and anti-CTLA-A mAb in several tumor animal models for both local tumor control and distant effects.Radiotherapy increases tumor immunogenicity in several preclinical models by increasing MHC molecules expression and is able to induce significant tumor reduction in around 30% of cases. Thus, combining radiotherapy and administration of ipilimumab could elicit systemic antitumor response. Radiation therapy will expose tumor-associated antigens (TAA) and facilitate antigen presentation, and further blockade of CTLA-4 could amplify the immune antitumor response. In this therapeutical model, the use of the own patient tumor as a source of tumor antigens (in opposition with other vaccination protocols, where TAA are exogenic) is particularly adapted.

PURPOSE: This Phase I trial determines the side effects and best dose of radiation therapy administered in combination with ipilimumab.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary: To determine the Maximum Tolerated Dose (MTD), Dose Limiting Toxicity (DLT) and recommended Phase 2 dose of radiation therapy administered in combination with ipilimumab.

Secondary:

Adverse event profiles Preliminary anti-tumor activity following escalating doses of radiation combined to ipilimumab using the immune related response criteria irRC overall survival in patients treated with this combination systemic immunologic anti tumor response intratumoral immune response pharmacodynamic effects of ipilimumab and radiotherapy in combination on Absolute Lymphocyte Count (ALC) associations between ALC and anti-tumor activity of ipilimumab and radiotherapy in combination

Study Type

Interventional

Enrollment (Actual)

19

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Villejuif, France, 94805
        • Institut Gustave Roussy
    • Val de Marne
      • Villejuif, Val de Marne, France, 94805
        • Gustave Roussy Cancer Campus

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Willing and able to give written informed consent.
  • Histologic diagnosis of melanoma.
  • Unresectable locally advanced or metastatic melanoma with at least one melanoma metastasis accessible to radiation therapy.
  • Measurable disease according to immune related Response Criteria
  • Required values for initial laboratory tests:

WBC >= 2000/uL ANC >= 1000/uL Platelets >= 75 x 103/uL Hemoglobin >= 8 g/dL Creatinine <= 2,5 x ULN AST/ALT <= 2.5 x ULN for patients without liver metastasis or <= 5 x ULN for patients with liver metastasis Total Bilirubin <= 1,5.x ULN, (except patients with Gilbert's Syndrome, who must have a total bilirubin less than 3.0 mg/dL)

  • No active or chronic infection with HIV, Hepatitis B, or Hepatitis C.
  • ECOG Performance status of 0 or 1.
  • Men and women, >= 18 years of age.
  • Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 8 weeks after the last dose of investigational product, in such a manner that the risk of pregnancy is minimized.

Exclusion Criteria:

  • Suspected or known CNS tumors including brain metastasis.
  • Any other malignancy form which the patient has been disease-free for less than 5 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix.
  • Autoimmune disease: Patients with a history of inflammatory bowel disease are excluded from this study, as are patients with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [e.g., Wegener's Granulomatosis]); motor neuropathy considered of autoimmune origin (e.g. Guillain-Barre Syndrome).
  • Any underlying medical or psychiatric condition, which in the opinion of the investigator will make the administration of ipilimumab hazardous or obscure the interpretation of AEs, such as a condition associated with frequent diarrhea.
  • Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to 1 month before or after any dose of ipilimumab).
  • A history of prior treatment with ipilimumab or prior CD137 agonist or CTLA-4 inhibitor or agonist.
  • Concomitant hormonal treatment, chemotherapy or immunotherapy.
  • Other investigational therapy.
  • Prior radiotherapy within the same body area.
  • Prior radiotherapy targeting fields containing flat bones.
  • Women of childbearing potential (WOCBP), defined above
  • Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness.
  • Persons of reproductive potential must agree to use an adequate method of contraception throughout treatment and for at least 8 weeks after ipilimumab is stopped.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: radiation therapy with Ipilimumab
Drug: Ipilimumab

Induction: Treatment with ipilimumab will be administered on weeks 1, 4, 7 and 10 at 10mg/kg.

Maintenance: Ipilimumab will be administered intravenously over 90-minutes at 10 mg/kg every 12 weeks starting at week 24, for as long as the treating physician believes that there is a clinical benefit or for as long as patient is tolerant of therapy

Radiation: Radiotherapy
Radiation therapy 9 Grays in 3 Grays fractions Radiation therapy 15 Grays in 5 Grays fractions Radiation therapy 18 Grays in 6 Grays fractions Radiation therapy 24 Grays in 8 Grays fractions

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum Tolerated Dose of radiation therapy administered in combination with ipilimumab
Time Frame: between week 4 and week 10
To determine the Maximum Tolerated Dose (MTD), Dose Limiting Toxicity (DLT) andrecommended Phase 2 dose of radiation therapy administered in combination with ipilimumab.
between week 4 and week 10

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse event profiles
Time Frame: At an average of every four weeks during the treatment phase
Adverse event profiles
At an average of every four weeks during the treatment phase
overall survival in patients treated with this combination
Time Frame: At an average of every four weeks during the treatment phase and then every three months during the follow-up phase
overall survival in patients treated with this combination
At an average of every four weeks during the treatment phase and then every three months during the follow-up phase

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Gustave Roussy, Cancer Campus, Grand Paris

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2011

Primary Completion (Actual)

November 1, 2015

Study Completion (Actual)

March 1, 2016

Study Registration Dates

First Submitted

March 16, 2011

First Submitted That Met QC Criteria

March 16, 2012

First Posted (Estimate)

March 19, 2012

Study Record Updates

Last Update Posted (Estimate)

June 9, 2016

Last Update Submitted That Met QC Criteria

June 8, 2016

Last Verified

June 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CSET 2010/1663 -Mel-Ipi-Rx
  • 2010-020317-93 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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