Description Module
The Description Module contains narrative descriptions of the clinical trial, including a brief summary and detailed description. These descriptions provide important information about the study's purpose, methodology, and key details in language accessible to both researchers and the general public.
Description Module path is as follows:
Study -> Protocol Section -> Description Module
Description Module
Ignite Creation Date:
2025-12-25 @ 4:36 AM
Ignite Modification Date:
2025-12-25 @ 4:36 AM
NCT ID:
NCT06603818
Brief Summary:
Background:
Metastatic colorectal cancer (mCRC) is cancer that has spread beyond the colon and rectum. Most people with mCRC die within 5 years. New immune-based treatments are making progress with some types of colon cancer. But these treatments do little for people with a type of cancer that is microsatellite stable (MSS). MSS is a specific cancer biomarker. Better treatments are needed.
Objective:
To test 2 drugs (tiragolumab and atezolizumab) combined with radiation therapy in people with MSS mCRC.
Eligibility:
People aged 18 years and older with MSS mCRC.
Design:
Participants will be screened. They will have a physical exam with blood tests. They will have imaging scans and a test of their heart function. They will provide a tissue sample from their tumor; if one is not already available, a new sample will be taken. Their ability to perform normal tasks will be assessed.
Tiragolumab and atezolizumab are both administered through a tube attached to a needle inserted into a vein. Participants will receive both drugs on day 1 of 3-week treatment cycles. Each study visit should last about 8 hours.
Participants will receive radiation therapy on days 1, 3, and 5 of cycle 1 only.
Blood samples and rectal swabs will be collected on day 1 of every cycle.
Imaging scans will be repeated every 9 weeks. Additional tumor samples may be taken during treatment.
Treatment will continue for up to 2 years.
Participants will have a follow-up visit 1 month after treatment ends. Follow-up visits will continue every 3 months for 1 more year.
Detailed Description:
Background:
* Metastatic colorectal cancer (mCRC) is incurable for most patients and carries a poor diagnosis.
* Immune-based approaches in solid tumor malignancies have seen much progress but these have limited efficacy for microsatellite stable (MSS) mCRC.
* The Gastrointestinal Malignancies Section at NCI conducted a Pilot Study of the PD-1 Targeting Agent AMP-224 with low-dose cyclophosphamide and stereotactic body radiation therapy (SBRT) that supports potential antitumor efficacy of the combination of immunotherapy and radiation in MSS mCRC (NCT02298946).
* T cell immunoreceptor with Ig and ITIM domains (TIGIT) is an inhibitory receptor expressed in multiple cancers on tumor-infiltrating cytotoxic T cells, helper T cells, natural killer (NK) cells, and regulatory T cells. Its main ligand, CD155, is expressed on tumor-infiltrating myeloid cells and upregulated on cancer cells, contributing to local immune-surveillance suppression.
* Among inhibitory immune checkpoint molecules, a unique property of TIGIT blockade is that it enhances not only anti-tumor effector T-cell responses, but also NK-cell responses, and reduces the suppressive capacity of regulatory T cells.
* Pre-clinical studies show that the co-blockade of TIGIT and the programmed cell death protein 1 (PD-1) / programmed cell death ligand 1 (PD-L1) pathway may lead to decreased tumor volume. Notably, this has been observed in anti-PD-1 resistant tumor models.
* Preclinical and clinical evidence suggests further increased benefit to the double immune checkpoint blockade through increased expression of PD-L1 and neoantigens in response to SBRT.
* Early results from clinical trials suggest clinical activity of anti-TIGITplus anti-PD-L1 in solid tumors and the effect of combining immunotherapy with radiation in heavily pretreated MSS mCRC patients providing a proof of concept that radiation enhances immunotherapy response.
* A combination of anti-PD-L1, anti-TIGIT, and SBRT may increase CRC susceptibility to immune therapy given the promising activity of anti-TIGIT in combination with anti-PDL1 in preclinical studies of mice bearing subcutaneous CT26 colon tumors.
Primary Objectives:
* To confirm the Recommended Phase II dose (RP2D) of the combination therapy (tiragolumab and atezolizumab plus SBRT) in participants with MSS mCRC (Part A)
* To determine the proportion of participants without progression after 9 weeks of the combination therapy (tiragolumab and atezolizumab plus SBRT) in participants with MSS mCRC (Part B)
Eligibility:
* Age \>= 18 years
* Eastern Cooperative Oncology Group (ECOG) performance status \<= 1
* Histopathologic confirmation of mCRC by the NCI Laboratory of Pathology (LP)
* Disease not amenable to curative resection
* At least 1 lesion amenable to SBRT and a second lesion outside the radiation field to serve as a target lesion
* Adequate organ and marrow function
Design:
* This is a phase II, single-arm, non-randomized, trial using tiragolumab and atezolizumab in combination with SBRT.
* A maximum of 30 participants with MSS mCRC will be enrolled.
* Participants will receive atezolizumab and tiragolumab intravenously (IV) every 3 weeks (21-day cycles) with SBRT occurring on Days 1, 3, and 5 of Cycle 1 for 2 years.
* Participants will be evaluated routinely for toxicity and will have re-staging imaging every 9 weeks (every 3 cycles).
* Optional research biopsies will be done at baseline and during week 1 of cycle 2. If the participant has disease progression after cycle 3, a post-treatment biopsy may be performed.
* The proportion of participants that are progression-free at 9 weeks will be evaluated as a binary endpoint.
Study:
NCT06603818
Study Brief:
Protocol Section:
NCT06603818