Clinical trial NCT02843165: Checkpoint Blockade Immunotherapy Combined With Stereotactic Body Radiation in Advanced Metastatic Disease
Official title: Randomized Phase II Study of Checkpoint Blockade Immunotherapy Combined With Stereotactic Body Radiation Therapy in Advanced Metastatic Disease
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Metastatic Cancer
Keywords: stereotactic body radiation therapy
checkpoint blockade immunotherapy
Lead sponsor: University of California, San Diego
Sponsor class: OTHER
First posted: 2016-07-25
Enrollment: 146
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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 ≤ 2.
* 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.

Primary outcomes:
measure: Objective Response Rate
timeFrame: Responses measured by RECIST at 16 weeks from baseline
Secondary outcomes:
measure: Safety and toxicity of combined CBI plus SBRT
timeFrame: Evaluated at each treatment cycle (each cycle is 2 or 3 weeks), then at 8 weeks, 16 weeks, 6 months, 12 months, 18 months, and 24 months, then every 6 months up to 2 years
measure: Progression Free Survival
timeFrame: Assessed at 5 years
measure: Overall Survival
timeFrame: Assessed at 5 years
measure: Rate of Stable Disease
timeFrame: Assessed at 5 years
measure: Change in anti-tumor immune response
timeFrame: At week 3 or 4 after starting treatment (prior to Cycle 2 of CBI) and at 2 months. Each cycle is 2 or 3 weeks.
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: UCSD Moores Cancer Center
state: California
Study officials:
affiliation: University of California, San Diego
name: Andrew Sharabi, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: