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.
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
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
19
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 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
Gustave Roussy Cancer Campus
Villejuif, Val de Marne, France
Institut Gustave Roussy
Villejuif, France
Maximum Tolerated Dose of radiation therapy administered in combination with ipilimumab
To determine the Maximum Tolerated Dose (MTD), Dose Limiting Toxicity (DLT) andrecommended Phase 2 dose of radiation therapy administered in combination with ipilimumab.
Time frame: between week 4 and week 10
Adverse event profiles
Adverse event profiles
Time frame: At an average of every four weeks during the treatment phase
overall survival in patients treated with this combination
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
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