Phase II Trial of Stereotactic Body Radiotherapy Followed by Ipilimumab in Treating Patients With Stage IV Melanoma

NCT01970527 | Terminated Phase 2 Results

• 3 other identifiers: 9031NCI-2013-01757P30CA015704
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well stereotactic body radiotherapy and ipilimumab work in treating patients with stage IV melanoma. Stereotactic body radiotherapy (SBRT) may be able to send x-rays directly to the tumor and cause less damage to normal tissue. Monoclonal antibodies, such as ipilimumab, target certain cells to interfere with the ability of tumor cells to grow and spread. Giving SBRT with ipilimumab may kill more tumor cells.

Conditions

Recurrent Melanoma; Stage IV Skin Melanoma

Outcome Measures

Primary Outcomes (4)

• Immune-related Clinical Response, Defined as Proportion of Patients Treated at the Maximum-tolerated Dose (MTD) Who Achieve Either a Complete or Partial Immune-related Response

  Scored on a non-index lesion using immune-related response criteria according to immune-related Response Evaluation Criteria in Solid Tumors version 1.1. The number of immune-related responses will be tabled by stratum and SBRT fraction dose level. At the MTD, the immune-related response rate and 95% exact confidence interval will be estimated separately for previously untreated and previously treated metastatic patients.

  Up to 60 days after last ipilimumab injection

• Immune-related Progression-free Survival (irPFS)

  irPFS will be estimated by the Kaplan-Meier method separately for previously untreated and previously treated metastatic patients who were treated at the MTD.. For some patients no scans were available for irRECIST reads, in which case change of management was determined to be the point of progression.

  Time from first day of radiotherapy to first documented immune-related progressive disease, death due to any cause or last patient contact alive and progression-free, assessed at 6 months

• Late Toxicities, Graded According to the Radiation Therapy Oncology Group/European Organization for Research, the Treatment of Cancer Late Morbidity Scoring System, and the Common Terminology Criteria for Adverse Events Version 4.0

  Defined generally as an adverse event associated with the treatment which occurs beyond 30 days after last injection (i.e., adverse events which are observed months after treatment are most likely associated with SBRT). All dose-limiting toxicities and late toxicities will be graded and tabled by lesion site stratum and SBRT fraction dose level. Toxicity attribution to either SBRT or ipilimumab will be described if possible.

  Up to 3 years

• Overall Survival

  Will be estimated by the Kaplan-Meier method separately for previously untreated and previously treated metastatic patients who were treated at the MTD.

  Time from first day of radiotherapy to death due to any cause or last patient contact alive, assessed at 12 months

Study Arms (1)

Treatment (stereotactic body radiotherapy, ipilimumab)

EXPERIMENTAL

Patients undergo a total of 3 fractions of stereotactic body radiotherapy between days 1-13. Patients then receive ipilimumab IV every 3 weeks. Treatment repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity.

Biological: Ipilimumab; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Radiation: Stereotactic Body Radiation Therapy

Interventions

Ipilimumab BIOLOGICAL

Given IV

Also known as: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, MDX-010, MDX-CTLA4, Yervoy

Treatment (stereotactic body radiotherapy, ipilimumab)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (stereotactic body radiotherapy, ipilimumab)

Pharmacological Study OTHER

Correlative studies

Treatment (stereotactic body radiotherapy, ipilimumab)

Stereotactic Body Radiation Therapy RADIATION

Undergo SBRT

Also known as: SBRT

Treatment (stereotactic body radiotherapy, ipilimumab)

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed diagnosis of melanoma
• Previously treated or previously untreated stage IV melanoma by American Joint Committee on Cancer (AJCC) staging criteria
• Presence of an index lesion between 1 and 5 cm
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
• Signed informed consent document
• Adequate renal, hepatic, and hematologic indices for ipilimumab therapy
• Ability to tolerate stereotactic body radiation therapy (e.g. lie flat and hold position for treatment)

You may not qualify if:

• Prior systemic therapy within 14 days of study enrollment; patients must be adequately recovered from prior systemic therapy side effects as deemed by the treating investigator
• Clinical contraindication to stereotactic body radiotherapy (e.g. active systemic sclerosis, active inflammatory bowel disease if bowel is within target field, etc)
• Presence of central nervous system metastasis (including active brain metastasis); active brain metastasis would be defined as untreated brain metastases; if the brain metastases have received prior treatment (usually either with surgery or radiation), they are no longer active
• Long-term use of systemic corticosteroids; patients with replacement steroids and not immunosuppressive steroids may enroll in the study
• Prior radiation therapy (RT) that precludes the delivery of SBRT

Sponsors & Collaborators

• University of Washington: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

Ipilimumab; CTLA-4 Antigen; Radiosurgery

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immune Checkpoint Proteins; Costimulatory and Inhibitory T-Cell Receptors; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins; Antigens, Differentiation, T-Lymphocyte; Antigens, Differentiation; Antigens, Surface; Antigens; Biological Factors; Biomarkers; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Limitations and Caveats

We stopped this trial early as the standard of care shifted during the course of the study. Participant flow, Baseline Characteristics and Adverse events were recorded as appropriate for the 23 patients (22 evaluable) who consented to the trial.

Results Point of Contact

• Title: Dr. Ramesh Rengan
• Organization: University of Washington Medical Center

rengan@uw.edu

206-598-4100

Study Officials

• Ramesh Rengan

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2013
• First Posted: October 28, 2013
• Study Start: March 1, 2014
• Primary Completion: November 3, 2018
• Study Completion: June 21, 2019
• Last Updated: February 13, 2020
• Results First Posted: February 13, 2020

Record last verified: 2020-01

Locations

US (1)