Trial of SBRT With Concurrent Ipilimumab in Metastatic Melanoma

NCT02406183 | Completed Phase 1

• 1 other identifier: EC 2015/0025
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

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.

Conditions

Melanoma; Effects of Immunotherapy; Adverse Effect of Radiation Therapy

Outcome Measures

Primary Outcomes (1)

• Maximal tolerated dose (MDT) that is associated with dose-limiting toxicity (DLT) in 25% of patients.

  2 years

Secondary Outcomes (7)

• Preliminary anti-tumor activity following escalating doses of radiation combined to ipilimumab using the immune related response criteria irRC

  2 years

• Overall survival

  2 years

• Progression-free survival

  2 years

• Immunomonitoring (absolute lymphocyte count)

  2 years

• Immunomonitoring (frequencies of Foxp3+ Treg-cells)

  2 years

Study Arms (1)

Treatment (SBRT, Ipilimumab)

EXPERIMENTAL

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

Radiation: Stereotactic body radiotherapy (SBRT); Drug: Ipilimumab

Interventions

Stereotactic body radiotherapy (SBRT) RADIATION

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

Also known as: SABR

Treatment (SBRT, Ipilimumab)

Ipilimumab DRUG

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

Also known as: Yervoy

Treatment (SBRT, Ipilimumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Radiotherapie: lead

Study Sites (1)

Dept. of Radiotherapy, Ghent University Hospital

Ghent, Oost-Vlaanderen, 9000, Belgium

Location

MeSH Terms

Conditions

Melanoma; Radiation Injuries

Interventions

Radiosurgery; Ipilimumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Piet Ost, MD, PhD

  University Hospital, Ghent

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: March 17, 2015
• First Posted: April 2, 2015
• Study Start: March 1, 2015
• Primary Completion: August 1, 2016
• Study Completion: August 1, 2016
• Last Updated: January 10, 2017

Record last verified: 2017-01

Locations

BE (1)