Ignite Creation Date:
2024-10-26 @ 3:40 PM
Last Modification Date:
2024-10-26 @ 3:40 PM
Study NCT ID:
NCT06603818
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-09-17
Brief Title:
Immunotherapies in Combination With Stereotactic Body Radiation Radiotherapy in Microsatellite Stable MSS Metastatic Colorectal Cancer mCRC
Sponsor:
None
Organization:
None
Study Overview
Official Title:
A Phase II Study of Immunotherapies Tiragolumab and Atezolizumab in Combination With Stereotactic Body Radiation Radiotherapy in Microsatellite Stable MSS Metastatic Colorectal Cancer mCRC
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-10-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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
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
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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None