Trial of SBRT With Concurrent Ipilimumab in Metastatic Melanoma

NCT ID: NCT02406183

Last Updated: 2017-01-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-03-31
• Study Completion Date: 2016-08-31

Brief Summary

The prognosis of advanced metastatic melanoma remains poor although a breakthrough has been achieved with the novel anti-CTLA-4 treatment (ipilimumab) for a subset of patients. Unfortunately, due to immune resistance, the majority of patients do not obtain long-lasting clinical benefit. Radiotherapy is able to interfere with immune resistance by inducing immunogenic cell death. Preclinical evidence indicates that combining radiotherapy with anti-CTLA-4 treatment increases response rates compared to single agent treatment. These data are supported by several spectacular clinical cases and one retrospective study. The investigators hypothesize that combining ipilimumab with radiotherapy will result in a higher response rate compared to ipilimumab or radiotherapy in monotherapy. Given the complexity of the interaction in anti-tumor immunity, the first goal of this project is to assess the safety of the combined treatment.

Detailed Description

The safety profiles of ipilimumab and SBRT are well studied separately 22-24, but prospective data on the combination of ipilimumab and high-dose SBRT are lacking. Consequently, the first goal of the proposed prospective phase I trial is to assess the safety (dose limiting toxicity, DLT) of the combination of high-dose SBRT and ipilimumab in patients with advanced melanoma.

Conditions

Melanoma; Effects of Immunotherapy; Adverse Effect of Radiation Therapy

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (SBRT, Ipilimumab)

Drug: Ipilimumab Dosage: Ipilimumab will be administered intravenously at 3 mg/kg every 3 weeks for 4 cycles,

Radiation: Stereotactic Body Radiotherapy Radiation therapy 24 Grays in 8 Grays fractions, Radiation therapy 30 Grays in 10 Grays fractions, Radiation therapy 36 Grays in 12 Grays fractions

Group Type: EXPERIMENTAL

Stereotactic body radiotherapy (SBRT)

Intervention Type: RADIATION

The SBRT dose will be escalated in 3 steps as described above and will be given on d39, d41 and d43

Ipilimumab

Intervention Type: DRUG

Ipilimumab 3mg/kg will be given IV on d1, d22, d43 and d64

Interventions

Stereotactic body radiotherapy (SBRT)

The SBRT dose will be escalated in 3 steps as described above and will be given on d39, d41 and d43

Intervention Type: RADIATION

Ipilimumab

Ipilimumab 3mg/kg will be given IV on d1, d22, d43 and d64

Intervention Type: DRUG

Other Intervention Names

SABR; Yervoy

Eligibility Criteria

Inclusion Criteria

• Signed informed consent and willingness to comply to the treatment and follow-up
• Histological diagnosis of melanoma,
• at least 3 extracranial measurable metastatic lesions per RECIST 1.1,
• Karnofsky Performance score >60,
• Age ≥18,
• Life expectancy ≥ 16 weeks
• Women of childbearing potential must have a negative serum pregnancy test within 14 days of first dose of study treatment. Men and women should agree to use effective contraception, during the study and for 1 month following the last dose of investigational product.
• ≥ 28 days between last treatment with standard or experimental chemotherapy, surgery, radiotherapy, cytokine therapy or immunotherapy. Patient should be completely recuperated of any clinical toxicity developed during previous treatments.
• Patients should have adequate organ function for ipilimumab treatment

Exclusion Criteria

• Central nervous system (CNS) metastases at baseline, with the exception of those subjects who have previously-treated CNS metastases (surgery ± radiotherapy, radiosurgery, or gamma knife) and who meet both of the following criteria: a) are asymptomatic and b) have no requirement for steroids or enzyme-inducing anticonvulsants.
• Prior malignancy: Subjects who have had another malignancy and have been disease-free for 5 years, or subjects with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible
• Prior radiotherapy preventing treatment with SBRT.
• Disorder precluding understanding of trial information.
• Autoimmune disease: Patients with a history of inflammatory bowel disease (including Crohn's disease and ulcerative colitis) and autoimmune disorders such as rheumatoid arthritis, systemic progressive sclerosis [scleroderma], Systemic Lupus Erythematosus or autoimmune vasculitis [e.g., Wegener's Granulomatosis] are excluded from this study.
• Known Human Immunodeficiency Virus (HIV), Hepatitis B, or Hepatitis C.
• Concomitant therapy with any of the following: IL-2, interferon or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other investigational therapies; or chronic use of systemic corticosteroids (used in the management of cancer or non-cancer-related illnesses).
• Pregnant women
• Breast feeding
• History of or current immunodeficiency disease or prior treatment compromising immune function, prior allogeneic stem cell transplantation.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Radiotherapie

OTHER

Sponsor Role: lead

Responsible Party

Radiotherapie

MD, PhD

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Piet Ost, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Ghent

Locations

Dept. of Radiotherapy, Ghent University Hospital

Ghent, Oost-Vlaanderen, Belgium

Countries

Belgium

Other Identifiers

EC 2015/0025

Identifier Type: -

Identifier Source: org_study_id