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

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Gustave Roussy, Cancer Campus, Grand Paris
Sponsor:
Information provided by (Responsible Party):
Gustave Roussy, Cancer Campus, Grand Paris
ClinicalTrials.gov Identifier:
NCT01557114
First received: March 16, 2011
Last updated: June 6, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention Phase
Malignant Melanoma
Drug: Ipilimumab
Radiation: Radiotherapy
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Gustave Roussy, Cancer Campus, Grand Paris:

Primary Outcome Measures:
  • Maximum Tolerated Dose of radiation therapy administered in combination with ipilimumab [ Time Frame: between week 4 and week 10 ] [ Designated as safety issue: Yes ]
    To determine the Maximum Tolerated Dose (MTD), Dose Limiting Toxicity (DLT) andrecommended Phase 2 dose of radiation therapy administered in combination with ipilimumab.


Secondary Outcome Measures:
  • Adverse event profiles [ Time Frame: At an average of every four weeks during the treatment phase ] [ Designated as safety issue: Yes ]
    Adverse event profiles

  • 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 ] [ Designated as safety issue: Yes ]
    overall survival in patients treated with this combination


Estimated Enrollment: 30
Study Start Date: March 2011
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01557114

Contacts
Contact: Caroline ROBERT, MD, PHD 33 1 42 11 42 53 caroline.robert@igr.fr
Contact: Eric DEUTSCH, MD, PHD 33 1 42 11 65 73 eric.deutsch@igr.fr

Locations
France
Gustave Roussy Cancer Campus Recruiting
Villejuif, Val de Marne, France, 94805
Contact: Caroline Robert, MD    0142114210 ext +33    caroline.robert@gustaveroussy.fr   
Contact: Valérie Mairot    0142116643 ext +33    valerie.mairot@gustaveroussy.fr   
Institut Gustave Roussy Active, not recruiting
Villejuif, France, 94805
Sponsors and Collaborators
Gustave Roussy, Cancer Campus, Grand Paris
  More Information

No publications provided

Responsible Party: Gustave Roussy, Cancer Campus, Grand Paris
ClinicalTrials.gov Identifier: NCT01557114     History of Changes
Other Study ID Numbers: CSET 2010/1663 -Mel-Ipi-Rx, 2010-020317-93
Study First Received: March 16, 2011
Last Updated: June 6, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Gustave Roussy, Cancer Campus, Grand Paris:
unresectable Stage III or stage IV advanced malignant melanoma

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas

ClinicalTrials.gov processed this record on September 22, 2014