Phase II/III study of circulating tumor DNA as a predictive biomarker in adjuvant chemotherapy in patients with stage II colon cancer:NRG-GI005 (COBRA).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. TPS148-TPS148
Author(s):  
Van K. Morris ◽  
Greg Yothers ◽  
Scott Kopetz ◽  
Samuel A. Jacobs ◽  
Peter C. Lucas ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Colon Cancer ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Phase Ii ◽  
Predictive Biomarkers ◽  
Circulating Tumor Dna ◽  
Stage Ii ◽  
Phase Iii ◽  
Tumor Dna

TPS148 Background: There are currently no validated predictive biomarkers for stage II resected colon cancer (CC) after adjuvant chemotherapy. However, circulating tumor DNA (ctDNA) that is shed into the bloodstream represents a highly specific and sensitive approach for identifying microscopic or residual tumor cells. For patients (pts) with CC, the detection of ctDNA is associated with persistent disease after resection and may outperform traditional clinical and pathological features as a prognostic factor to assess risk for recurrence. We hypothesize that for pts whose stage II colon cancer has been resected and who have no traditional high-risk features, a positive ctDNA status may identify those who will benefit from adjuvant chemotherapy. Methods: In this prospective phase II/III clinical trial, pts (N=1,408) with resected stage II CC without traditional high-risk features and whom the evaluating oncologist deems suitable for no adjuvant chemotherapy will be randomized 1:1 into 2 arms:standard-of-care/observation (Arm A), or prospective testing for ctDNA (Arm B). Postoperative blood will be analyzed for ctDNA with the GuardantHealth LUNAR panel, covering CC-relevant mutations and CC-specific methylation profiling. Pts in Arm B with ctDNA detected will be treated with 6 months of adjuvant (FOLFOX) chemotherapy. For all pts in Arm A, ctDNA status will be analyzed retrospectively at the time of endpoint analysis. The primary endpoints are clearance of ctDNA with adjuvant chemotherapy (phase II) and recurrence-free survival (RFS) for “ctDNA-detected” pts treated with or without adjuvant chemotherapy (phase III). Secondary endpoints will include time-to-event outcomes (OS, RFS, TTR) by ctDNA marker status and treatment, prevalence of detectable ctDNA in stage II CC, and rates of compliance with assigned intervention. Archived normal and matched tumor and blood samples will be collected for exploratory correlative research. The trial is actively accruing towards the phase II endpoint across all US and Canadian cooperative groups. Support:U10-CA-180868, -180822; UG1CA-189867; GuardantHealth. Clinical trial information: NCT04068103.

NRG-GI005 (COBRA): Phase II/III study of circulating tumor DNA as a predictive biomarker in adjuvant chemotherapy in patients with stage II colon cancer.

2020 ◽  
Vol 38 (4_suppl) ◽  
pp. TPS261-TPS261
Author(s):  
Van K. Morris ◽  
Greg Yothers ◽  
Scott Kopetz ◽  
Samuel A. Jacobs ◽  
Peter C. Lucas ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Colon Cancer ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Phase Ii ◽  
Circulating Tumor Dna ◽  
Stage Ii ◽  
Phase Iii ◽  
Stage Ii Colon Cancer ◽  
Tumor Dna

TPS261 Background: There are currently no validated predictive biomarkers for stage II resected colon cancer (CC) after adjuvant chemotherapy. However, circulating tumor DNA (ctDNA) that is shed into the bloodstream represents a highly specific and sensitive approach for identifying microscopic or residual tumor cells. For patients (pts) with CC, the detection of ctDNA is associated with persistent disease after resection and may outperform traditional clinical and pathological features as a prognostic factor to assess risk for recurrence. We hypothesize that for pts whose stage II colon cancer has been resected and who have no traditional high-risk features, a positive ctDNA status may identify those who will benefit from adjuvant chemotherapy. Methods: In this prospective phase II/III clinical trial, pts (N=1,408) with resected stage II CC without traditional high-risk features and whom the evaluating oncologist deems suitable for no adjuvant chemotherapy will be randomized 1:1 into 2 arms: standard-of-care/observation (Arm A), or prospective testing for ctDNA (Arm B). Postoperative blood will be analyzed for ctDNA with the GuardantHealth LUNAR panel, covering CC-relevant mutations and CC-specific methylation profiling. Pts in Arm B with ctDNA detected will be treated with 6 months of adjuvant (FOLFOX) chemotherapy. For all pts in Arm A, ctDNA status will be analyzed retrospectively at the time of endpoint analysis. The primary endpoints are clearance of ctDNA with adjuvant chemotherapy (phase II) and recurrence-free survival (RFS) for “ctDNA-detected” pts treated with or without adjuvant chemotherapy (phase III). Secondary endpoints will include time-to-event outcomes (OS, RFS, TTR) by ctDNA marker status and treatment, prevalence of detectable ctDNA in stage II CC, and rates of compliance with assigned intervention. Archived normal and matched tumor and blood samples will be collected for exploratory correlative research. Trial accrual is anticipated across all US and Canadian cooperative groups.NCT#: 04068103. Support: U10-CA-180868, -180822; UG1CA-189867; GuardantHealth. Clinical trial information: 04068103.

Phase II/III study of circulating tumor DNA as a predictive biomarker in adjuvant chemotherapy in patients with stage II colon cancer: NRG-GI005 (COBRA).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. TPS4121-TPS4121
Author(s):  
Van K. Morris ◽  
Greg Yothers ◽  
Scott Kopetz ◽  
Samuel A. Jacobs ◽  
Peter C. Lucas ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Colon Cancer ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Phase Ii ◽  
Circulating Tumor Dna ◽  
Stage Ii ◽  
Phase Iii ◽  
Stage Ii Colon Cancer ◽  
Tumor Dna

TPS4121 Background: There are currently no validated predictive biomarkers for stage II resected colon cancer (CC) after adjuvant chemotherapy. However, circulating tumor DNA (ctDNA) that is shed into the bloodstream represents a highly specific and sensitive approach for identifying microscopic or residual tumor cells. For patients (pts) with CC, the detection of ctDNA is associated with persistent disease after resection and may outperform traditional clinical and pathological features as a prognostic factor to assess risk for recurrence. We hypothesize that for pts whose stage II colon cancer has been resected and who have no traditional high-risk features, a positive ctDNA status may identify those who will benefit from adjuvant chemotherapy. Methods: In this prospective phase II/III clinical trial, pts (N=1,408) with resected stage II CC without traditional high-risk features and whom the evaluating oncologist deems suitable for no adjuvant chemotherapy will be randomized 1:1 into 2 arms: standard-of-care/observation (Arm A), or prospective testing for ctDNA (Arm B). Postoperative blood will be analyzed for ctDNA with the GuardantHealth LUNAR panel, covering CC-relevant mutations and CC-specific methylation profiling. Pts in Arm B with ctDNA detected will be treated with 6 months of adjuvant (FOLFOX) chemotherapy. For all pts in Arm A, ctDNA status will be analyzed retrospectively at the time of endpoint analysis. The primary endpoints are clearance of ctDNA with adjuvant chemotherapy (phase II) and recurrence-free survival (RFS) for “ctDNA-detected” pts treated with or without adjuvant chemotherapy (phase III). Secondary endpoints will include time-to-event outcomes (OS, RFS, TTR) by ctDNA marker status and treatment, prevalence of detectable ctDNA in stage II CC, and rates of compliance with assigned intervention. Archived normal and matched tumor and blood samples will be collected for exploratory correlative research. The trial is actively accruing towards the phase II endpoint across all US and Canadian cooperative groups. Support: U10-CA-180868, -180822; UG1CA-189867; GuardantHealth. Clinical trial information: NCT04068103 .

Phase II/III study of Circulating tumOr DNA as a predictive BiomaRker in Adjuvant chemotherapy in patients with stage II colon cancer: NRG-GI005 (COBRA).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS3622-TPS3622
Author(s):  
Van K. Morris ◽  
Greg Yothers ◽  
Scott Kopetz ◽  
Samuel A. Jacobs ◽  
Peter C. Lucas ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Colon Cancer ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Phase Ii ◽  
Circulating Tumor Dna ◽  
Stage Ii ◽  
Phase Iii ◽  
Stage Ii Colon Cancer ◽  
Tumor Dna

TPS3622 Background: There are currently no validated predictive biomarkers for stage II resected colon cancer (CC) after adjuvant chemotherapy. However, circulating tumor DNA (ctDNA) that is shed into the bloodstream represents a highly specific and sensitive approach for identifying microscopic or residual tumor cells. For patients (pts) with CC, the detection of ctDNA is associated with persistent disease after resection and may outperform traditional clinical and pathological features as a prognostic factor to assess risk for recurrence. We hypothesize that for pts whose stage II colon cancer has been resected and who have no traditional high-risk features, a positive ctDNA status may identify those who will benefit from adjuvant chemotherapy. Methods: In this prospective phase II/III clinical trial, pts (N = 1,408) with resected stage II CC without traditional high-risk features and whom the evaluating oncologist deems suitable for no adjuvant chemotherapy will be randomized 1:1 into 2 arms: standard-of-care/observation (Arm A), or prospective testing for ctDNA (Arm B). Postoperative blood will be analyzed for ctDNA with the GuardantHealth LUNAR panel, covering CC-relevant mutations and CC-specific methylation profiling. Pts in Arm B with ctDNA detected will be treated with 6 months of adjuvant (FOLFOX) chemotherapy. For all pts in Arm A, ctDNA status will be analyzed retrospectively at the time of endpoint analysis. The primary endpoints are clearance of ctDNA with adjuvant chemotherapy (phase II) and recurrence-free survival (RFS) for “ctDNA-detected” pts treated with or without adjuvant chemotherapy (phase III). Secondary endpoints will include time-to-event outcomes (OS, RFS, TTR) by ctDNA marker status and treatment, prevalence of detectable ctDNA in stage II CC, and rates of compliance with assigned intervention. Archived normal and matched tumor and blood samples will be collected for exploratory correlative research. The trial is actively accruing towards the phase II endpoint in North America. NCT#: 04068103. Support: U10-CA-180868, -180822; UG1CA-189867; GuardantHealth. Clinical trial information: NCT04068103.

scholarly journals Circulating tumor DNA guided adjuvant chemotherapy in stage II colon cancer (MEDOCC-CrEATE): study protocol for a trial within a cohort study

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
S. J. Schraa ◽  
◽  
K. L. van Rooijen ◽  
D. E. W. van der Kruijssen ◽  
C. Rubio Alarcón ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cohort Study ◽  
Adjuvant Chemotherapy ◽  
Study Protocol ◽  
Circulating Tumor Dna ◽  
Stage Ii ◽  
Stage Ii Colon Cancer ◽  
Tumor Dna

scholarly journals Oxaliplatin-based adjuvant chemotherapy duration (3 versus 6 months) for high-risk stage II colon cancer: the randomized phase III ACHIEVE-2 trial

2021 ◽  
Vol 32 (1) ◽  
pp. 77-84
Author(s):  
K. Yamazaki ◽  
T. Yamanaka ◽  
M. Shiozawa ◽  
D. Manaka ◽  
M. Kotaka ◽  
...  
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Stage Ii ◽  
Phase Iii ◽  
Stage Ii Colon Cancer

Abstract CT251: MEDOCC-CrEATE trial in progress: effectiveness of adjuvant chemotherapy in stage II colon cancer patients with positive circulating tumor DNA

2021 ◽  
Author(s):  
Suzanna J. Schraa ◽  
Karlijn L. Van Rooijen ◽  
Dave E. Van Der Kruijssen ◽  
Carmen Rubio Alarcón ◽  
Jillian Phallen ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Cancer Patients ◽  
Circulating Tumor Dna ◽  
Stage Ii ◽  
Stage Ii Colon Cancer ◽  
Tumor Dna

Phase II study of anti-EGFR rechallenge therapy with panitumumab driven by circulating tumor DNA molecular selection in metastatic colorectal cancer: The CHRONOS trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3506-3506
Author(s):  
Andrea Sartore-Bianchi ◽  
Filippo Pietrantonio ◽  
Sara Lonardi ◽  
Benedetta Mussolin ◽  
Francesco Rua ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Clinical Trial ◽  
Metastatic Colorectal Cancer ◽  
Phase Ii ◽  
Primary Endpoint ◽  
Liquid Biopsy ◽  
Objective Response ◽  
Circulating Tumor Dna ◽  
Type I ◽  
Tumor Dna

3506 Background: Despite advances in molecular segmentation of metastatic colorectal cancer (mCRC), beyond RAS status therapeutic actionability remains confined to the limited subgroups of ERBB2 amplified, BRAF mutated and MSI-H patients. Optimization of available treatments is therefore warranted. Rechallenge with anti-EGFR monoclonal antibodies is often empirically used with some benefit as late-line therapy. We previously found that mutant RAS and EGFR ectodomain clones, which emerge in blood during EGFR blockade, decline upon antibody withdrawal leading to regain drug sensitivity. Based on this rationale, we designed CHRONOS, a multicenter phase II trial of anti-EGFR therapy rechallenge guided by monitoring of the mutational status of RAS, BRAF and EGFR in circulating tumor DNA (ctDNA). To our knowledge, this is the first interventional clinical trial of liquid biopsy for driving anti-EGFR rechallenge therapy in mCRC. Methods: Eligible patients were PS ECOG 0-2 RAS/BRAF WT mCRC having first achieved an objective response and then progression in any treatment line with an anti-EGFR antibody containing regimen, displaying RAS, BRAF and EGFR ectodomain WT status in ctDNA at molecular screening after progression to the last anti-EGFR-free regimen. Clonal evolution in ctDNA was analyzed by ddPCR and next generation sequencing. Panitumumab 6 mg/kg was administered IV every two weeks until progression. The primary endpoint was objective response rate (ORR) by RECIST version 1.1 with independent central review. 27 total patients and 6 responses were required to declare the study positive (power = 85%, type I error = 0.05). Results: Between Aug 19, 2019 and Nov 6, 2020 52 patients were screened by liquid biopsy and 36 (69%) were negative in ctDNA for RAS/BRAF/EGFR mutations. Of these, 27 patients were enrolled in 4 centers. Median age was 64 years (range: 42-80). PS ECOG was 0/50%, 1/46%, 2/4%. Previous anti-EGFR was administered in 1st line in 63%, 2nd in 15% and > 2nd in 22%. Median number of previous treatments was 3. The primary endpoint was met, with 8/27 partial responses (PR) observed (2 unconfirmed) (ORR = 30%, 95% CI: 12-47%). Stable disease (SD) was obtained in 11/27 (40%, 95% CI: 24-59%), lasting > 4 months in 8/11. Disease control rate (PR plus SD > 4 months) was therefore obtained in 16/27 (59%, 95% CI: 41-78%). Median progression-free survival was 16 weeks. Median duration of response was 17 weeks (1 ongoing). Maximal grade toxicity was G3, limited to dermatological and occurring in 19% of patients. ctDNA dynamics were studied in all patients. Conclusions: Liquid biopsy-driven rechallenge with anti-EGFR antibodies leads to further objective responses in one third of patients. Genotyping tumor DNA in the blood to direct therapy can be effectively incorporated in the management of advanced CRCs. Clinical trial information: 2016-002597-12.

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