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Comparison of High-dose IL-2 and High-dose IL-2 With Radiation Therapy in Patients With Metastatic Melanoma. (SBRT/IL-2)

Primary Purpose

Metastatic Melanoma

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Radiation therapy and high-dose IL-2
High-dose IL-2
Sponsored by
Providence Health & Services
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Melanoma focused on measuring metastatic melanoma, IL-2, Interleukin 2, Radiation, Stereotactic Body Radiation Treatment, SBRT, Immunotherapy

Eligibility Criteria

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

Inclusion Criteria:

  • Histological confirmation of melanoma will be required by previous biopsy or cytology.
  • Patients must be ≥ 18 years of age.
  • Patients must have tumors amenable to SBRT in lungs, mediastinum, chest wall, bones (other than long bones), or liver (inclusive of immediately adjacent masses), 1 - 3 foci; no minimum size, but none greater than 7 cm. Patients may have other metastases but only a maximum of 3 will be treated.
  • ECOG performance status of 0-1.
  • Women of childbearing potential must have a serum or urine pregnancy test performed within 72 hours prior to the start of protocol treatment. The results of this test must be negative in order for the patient to be eligible. In addition, women of childbearing potential as well as male patients must agree to take appropriate precautions to avoid pregnancy.
  • Patients must sign a study-specific consent form.

Exclusion Criteria:

  • No metastatic site amenable to SBRT.
  • Patients with brain metastases not candidates for radiosurgery.
  • Previous radiation to sites proposed for radiation as part of this study.
  • Patients with active systemic, pulmonary, or pericardial infection.
  • Pregnant or lactating women.
  • Evidence of ischemia on exercise tolerance test, stress thallium study, or baseline EKG.
  • DLCO, FEV1 or FEV1/FVC less than 70% of predicted due to clinically significant underlying pulmonary disease. For any pulmonary function test values less than predicted values, the PI will review, and document the patient's suitability for high dose IL-2 therapy.
  • WBC < 3.0 x 109/L
  • Hgb < 9.0 g/dL
  • AST/ALT > 3 times the upper limit of the normal range
  • total bilirubin > 1.9 g/dL
  • creatinine > 1.9 g/dL
  • Patient requires chronic steroids.

Sites / Locations

  • Providence Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Arm A: IL-2 Monotherapy

Arm B: SBRT + IL-2

Arm Description

Patients receive standard high-dose IL-2 therapy, with an opportunity to crossover to the experimental arm if there is disease progression noted after two cycles of high-dose IL-2. Crossover patients will be included in Arm A.

Patients will receive two doses of radiation before receiving high-dose IL-2.

Outcomes

Primary Outcome Measures

Best Overall Tumor Response of High Dose IL-2 vs. SBRT + High Dose IL-2
Determine the best overall tumor response rate of high dose IL-2 versus SBRT + high-dose IL-2 using RECIST v1.1 assessed by CT/MRI, criteria applied to all target and non-target lesions with the exclusion of sites treated with SBRT. For patients who have SBRT after progression on IL-2 monotherapy, the response rate will be recorded, but not counted as a response for the primary objective. Overall response rate (ORR) includes all measurable and non-measurable target lesions except the lesions treated by SBRT, which were assessed separately. Both CT and positron emission tomography imaging were employed to assess response. Complete Response: disappearance of all target/non-target lesions and no abnormalities on PET; Partial Response: ≥30% decrease in sum of longest diameter (LD) of target lesions; Progressive Disease: ≥20% increase in sum of LD recorded since tx start or appearance of ≥1 new lesions; Stable Disease: Neither qualifying for PR nor PD since tx started.

Secondary Outcome Measures

Response Rate in Crossover Patients
Measure the response rate of patients who have disease progression after the first IL-2 cycles (using RECIST criteria) who received SBRT prior to cycle 3 of IL-2.

Full Information

First Posted
August 12, 2011
Last Updated
March 23, 2023
Sponsor
Providence Health & Services
Collaborators
Prometheus Laboratories
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1. Study Identification

Unique Protocol Identification Number
NCT01416831
Brief Title
Comparison of High-dose IL-2 and High-dose IL-2 With Radiation Therapy in Patients With Metastatic Melanoma.
Acronym
SBRT/IL-2
Official Title
Phase II Randomized Study of High Dose Interleukin-2 Versus Stereotactic Body Radiation (SBRT) and High Dose Interleukin-2 (IL-2) in Patients With Metastatic Melanoma
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
July 1, 2011 (Actual)
Primary Completion Date
April 5, 2017 (Actual)
Study Completion Date
December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Providence Health & Services
Collaborators
Prometheus Laboratories

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is compare the response rates in patients with metastatic melanoma treated with high-dose IL-2 to patients treated with high-dose IL-2 along with radiation therapy.
Detailed Description
All patients will receive high-dose IL-2. Half the patients enrolled will be randomly selected to receive radiation therapy to up to three tumors prior to receiving high-dose IL-2. Among the first 20 patients enrolled, those assigned to receive radiation will receive a single dose of radiation and for patients 21-44, those assigned to receive radiation will receive 2 doses of radiation.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Melanoma
Keywords
metastatic melanoma, IL-2, Interleukin 2, Radiation, Stereotactic Body Radiation Treatment, SBRT, Immunotherapy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
44 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm A: IL-2 Monotherapy
Arm Type
Active Comparator
Arm Description
Patients receive standard high-dose IL-2 therapy, with an opportunity to crossover to the experimental arm if there is disease progression noted after two cycles of high-dose IL-2. Crossover patients will be included in Arm A.
Arm Title
Arm B: SBRT + IL-2
Arm Type
Experimental
Arm Description
Patients will receive two doses of radiation before receiving high-dose IL-2.
Intervention Type
Other
Intervention Name(s)
Radiation therapy and high-dose IL-2
Other Intervention Name(s)
Interleukin 2, Stereotactic Body Radiation Therapy (SBRT)
Intervention Description
Patients 1 - 20 will receive a single fraction of radiation. Patients 21 through the completion of the study will receive two fractions. The dose for all patients will be 20 Gy per fraction to the prescription line at the edge of the planning treatment volume (PTV) with the last dose delivered on a Friday before IL-2 administration. For patients receiving two radiation doses, the doses can be administered on the Wednesday and Friday before IL-2 starts. Patients who are assigned to IL-2 monotherapy and have progressive disease after two IL-2 cycles are then eligible to receive SBRT before cycle 3 of IL-2 commences, single fraction for patients 1-20 and two fractions for patients 21- end of study.
Intervention Type
Drug
Intervention Name(s)
High-dose IL-2
Other Intervention Name(s)
Interleukin 2, Stereotactic Body Radiation Therapy (SBRT).
Intervention Description
IL-2 will be given on a Monday at a dose of 600,000 IU per kilogram IV every 8 hours for up to 14 doses each cycle. The second cycle is planned 16 days after cycle 1 but may be delayed up to one week to allow toxicity to resolve. The maximum number of doses that can be given during two cycles will be 28 doses. Patients who respond after two cycles can receive 4 more cycles of IL-2. Patients with disease progression after 2 cycles may elect to receive radiation before a 3rd cycle of IL-2. If patients crossover, IL-2 will be given on the Monday following the last dose of radiation, at a dose of 600,000 IU per kilogram IV every 8 hours for a maximum of 14 doses each cycle. Another cycle is planned 16 days after cycle 3 but may be delayed up to one week to allow toxicity to resolve.
Primary Outcome Measure Information:
Title
Best Overall Tumor Response of High Dose IL-2 vs. SBRT + High Dose IL-2
Description
Determine the best overall tumor response rate of high dose IL-2 versus SBRT + high-dose IL-2 using RECIST v1.1 assessed by CT/MRI, criteria applied to all target and non-target lesions with the exclusion of sites treated with SBRT. For patients who have SBRT after progression on IL-2 monotherapy, the response rate will be recorded, but not counted as a response for the primary objective. Overall response rate (ORR) includes all measurable and non-measurable target lesions except the lesions treated by SBRT, which were assessed separately. Both CT and positron emission tomography imaging were employed to assess response. Complete Response: disappearance of all target/non-target lesions and no abnormalities on PET; Partial Response: ≥30% decrease in sum of longest diameter (LD) of target lesions; Progressive Disease: ≥20% increase in sum of LD recorded since tx start or appearance of ≥1 new lesions; Stable Disease: Neither qualifying for PR nor PD since tx started.
Time Frame
At the end of Cycle 2 (Week 14).
Secondary Outcome Measure Information:
Title
Response Rate in Crossover Patients
Description
Measure the response rate of patients who have disease progression after the first IL-2 cycles (using RECIST criteria) who received SBRT prior to cycle 3 of IL-2.
Time Frame
7 weeks following Cycle 2 (Week 21).

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Histological confirmation of melanoma will be required by previous biopsy or cytology. Patients must be ≥ 18 years of age. Patients must have tumors amenable to SBRT in lungs, mediastinum, chest wall, bones (other than long bones), or liver (inclusive of immediately adjacent masses), 1 - 3 foci; no minimum size, but none greater than 7 cm. Patients may have other metastases but only a maximum of 3 will be treated. ECOG performance status of 0-1. Women of childbearing potential must have a serum or urine pregnancy test performed within 72 hours prior to the start of protocol treatment. The results of this test must be negative in order for the patient to be eligible. In addition, women of childbearing potential as well as male patients must agree to take appropriate precautions to avoid pregnancy. Patients must sign a study-specific consent form. Exclusion Criteria: No metastatic site amenable to SBRT. Patients with brain metastases not candidates for radiosurgery. Previous radiation to sites proposed for radiation as part of this study. Patients with active systemic, pulmonary, or pericardial infection. Pregnant or lactating women. Evidence of ischemia on exercise tolerance test, stress thallium study, or baseline EKG. DLCO, FEV1 or FEV1/FVC less than 70% of predicted due to clinically significant underlying pulmonary disease. For any pulmonary function test values less than predicted values, the PI will review, and document the patient's suitability for high dose IL-2 therapy. WBC < 3.0 x 109/L Hgb < 9.0 g/dL AST/ALT > 3 times the upper limit of the normal range total bilirubin > 1.9 g/dL creatinine > 1.9 g/dL Patient requires chronic steroids.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Brendan Curti, M.D.
Organizational Affiliation
Providence Health & Services
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Steven K. Seung, M.D.
Organizational Affiliation
Providence Health & Services
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Marka Crittenden, MD, PhD
Organizational Affiliation
Providence Health & Services
Official's Role
Principal Investigator
Facility Information:
Facility Name
Providence Cancer Center
City
Portland
State/Province
Oregon
ZIP/Postal Code
97213
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
32467299
Citation
Curti B, Crittenden M, Seung SK, Fountain CB, Payne R, Chang S, Fleser J, Phillips K, Malkasian I, Dobrunick LB, Urba WJ. Randomized phase II study of stereotactic body radiotherapy and interleukin-2 versus interleukin-2 in patients with metastatic melanoma. J Immunother Cancer. 2020 May;8(1):e000773. doi: 10.1136/jitc-2020-000773.
Results Reference
derived
PubMed Identifier
28428882
Citation
Sckisel GD, Mirsoian A, Minnar CM, Crittenden M, Curti B, Chen JQ, Blazar BR, Borowsky AD, Monjazeb AM, Murphy WJ. Differential phenotypes of memory CD4 and CD8 T cells in the spleen and peripheral tissues following immunostimulatory therapy. J Immunother Cancer. 2017 Apr 18;5:33. doi: 10.1186/s40425-017-0235-4. eCollection 2017.
Results Reference
derived

Learn more about this trial

Comparison of High-dose IL-2 and High-dose IL-2 With Radiation Therapy in Patients With Metastatic Melanoma.

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