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

Primary Purpose

Recurrent Melanoma, Stage IV Skin Melanoma

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Ipilimumab
Laboratory Biomarker Analysis
Pharmacological Study
Stereotactic Body Radiation Therapy
Sponsored by
University of Washington
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Melanoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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)

Exclusion Criteria:

  • 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metastases; if the brain metastases have received prior treatment (usually either with surgery or radiation), they are no longer active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

Sites / Locations

  • Fred Hutch/University of Washington Cancer Consortium

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (stereotactic body radiotherapy, ipilimumab)

Arm Description

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.

Outcomes

Primary Outcome Measures

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.
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.
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.
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.

Secondary Outcome Measures

Full Information

First Posted
October 22, 2013
Last Updated
January 31, 2020
Sponsor
University of Washington
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT01970527
Brief Title
Phase II Trial of Stereotactic Body Radiotherapy Followed by Ipilimumab in Treating Patients With Stage IV Melanoma
Official Title
RADVAX: A Stratified Phase II Dose Escalation Trial of Stereotactic Body Radiotherapy Followed by Ipilimumab in Metastatic Melanoma
Study Type
Interventional

2. Study Status

Record Verification Date
January 2020
Overall Recruitment Status
Terminated
Why Stopped
Change in standard of care
Study Start Date
March 2014 (undefined)
Primary Completion Date
November 3, 2018 (Actual)
Study Completion Date
June 21, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Washington
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.
Detailed Description
PRIMARY OBJECTIVES: I. To determine feasibility and immune-related clinical responses associated with SBRT when given in conjunction with ipilimumab. SECONDARY OBJECTIVES: I. To determine late toxicity and immune pharmacodynamic changes after SBRT followed by ipilimumab. OUTLINE: Patients undergo a total of 3 fractions of stereotactic body radiotherapy between days 1-13. Patients then receive ipilimumab intravenously (IV) every 3 weeks. Treatment repeats every 3 weeks for 4 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up within 60 days, and then every effort will be made to obtain records of patients during this follow up, and permission will be sought for the investigators and/or study team to re-contact the patient directly with regard to health status and toxicity.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Melanoma, Stage IV Skin Melanoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
23 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (stereotactic body radiotherapy, ipilimumab)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Ipilimumab
Other Intervention Name(s)
Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, MDX-010, MDX-CTLA4, Yervoy
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Intervention Type
Other
Intervention Name(s)
Pharmacological Study
Intervention Description
Correlative studies
Intervention Type
Radiation
Intervention Name(s)
Stereotactic Body Radiation Therapy
Other Intervention Name(s)
SBRT
Intervention Description
Undergo SBRT
Primary Outcome Measure Information:
Title
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
Description
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.
Time Frame
Up to 60 days after last ipilimumab injection
Title
Immune-related Progression-free Survival (irPFS)
Description
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 Frame
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
Title
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
Description
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.
Time Frame
Up to 3 years
Title
Overall Survival
Description
Will be estimated by the Kaplan-Meier method separately for previously untreated and previously treated metastatic patients who were treated at the MTD.
Time Frame
Time from first day of radiotherapy to death due to any cause or last patient contact alive, assessed at 12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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) Exclusion Criteria: 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ramesh Rengan
Organizational Affiliation
Fred Hutch/University of Washington Cancer Consortium
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fred Hutch/University of Washington Cancer Consortium
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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