Randomized Phase II Study of Checkpoint Blockade Immunotherapy Combined With Stereotactic Body Radiation Therapy in Advanced Metastatic Disease
Overview
- Phase
- Phase 2
- Intervention
- Checkpoint blockade immunotherapy plus SBRT
- Conditions
- Metastatic Cancer
- Sponsor
- University of California, San Diego
- Enrollment
- 106
- Locations
- 1
- Primary Endpoint
- Objective Response Rate
- Status
- Completed
- Last Updated
- 7 months ago
Overview
Brief Summary
The purpose of this study is to determine whether stereotactic body radiation therapy (SBRT) combined with checkpoint blockaded immunotherapy (CBI) will improve the response to the anticancer treatment compared to CBI alone in patients with advanced metastatic cancer.
Detailed Description
Patients who will receive anti-PD-1/PD-L1 immunotherapy with at least 1 site of measurable metastatic disease which will not be irradiated will be candidates for the study. Patients will be randomized (1:1) to CBI combined with SBRT or CBI alone. SBRT at 9.5Gy x3 fractions will be delivered within 1-21 days of the start of first cycle of CBI. The first six patients will be treated and observed for toxicity in the safety run-in phase for 30 days after radiation before continuing with further accrual. Radiation dose reduction is allowed if necessary to meet tissue constraints (6Gyx3 Minimum Dose). Response rates will be determined from the non-irradiated lesion/lesions. Blood draws will be obtained to analyze anti-tumor immune responses.
Investigators
Andrew Sharabi
Assistant Clinical Professor
University of California, San Diego
Eligibility Criteria
Inclusion Criteria
- •Patient has one lesion that is treatable with SBRT.
- •Patient has at least 1 site of measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria on computed tomography (CT) or Magnetic resonance imaging (MRI) which will not be irradiated.
- •Histological confirmation of malignancy (primary or metastatic tumor).
- •Patient may have any prior therapy allowed aside from having had prior radiotherapy to the treatment site.
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤
- •Patient's screening laboratory values must meet protocol limits.
- •Patient must have the ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria
- •Patient has had chemotherapy or radiotherapy within 4 weeks prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
- •Patient receiving any investigational or experimental agents other than immunotherapy.
- •Patient who has had any prior radiotherapy to the treatment site(s).
- •Patient is a pregnant woman (pregnant women are excluded from this study because radiation treatment has known potential for teratogenic or abortifacient effects).
- •Patient refuses to sign informed consent.
Arms & Interventions
Checkpoint blockade immunotherapy plus SBRT
Checkpoint blockade immunotherapy (CBI) plus stereotactic body radiation therapy (SBRT)
Intervention: Checkpoint blockade immunotherapy plus SBRT
Checkpoint blockade immunotherapy
Checkpoint blockade immunotherapy (CBI) alone
Intervention: Checkpoint blockade immunotherapy
Outcomes
Primary Outcomes
Objective Response Rate
Time Frame: Responses measured by RECIST at 16 weeks from baseline
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Secondary Outcomes
- Number of Participants With Adverse Events(up to 5 years)
- Progression Free Survival(Assessed at 5 years)
- Overall Survival(Assessed at 5 years)
- Rate of Stable Disease(Assessed at 5 years)