Establishing a ctDNA Biomarker to Improve Organ Preserving Strategies in Patients With Rectal Cancer
Study Details
Study Description
Brief Summary
This study measures the levels of circulating tumor DNA (ctDNA) in patients with stage II-III rectal cancer before, during, and after treatment to find out if the presence or absence of ctDNA in patient's blood using the Signatera test can be used to gauge how different treatments may affect rectal cancer. ctDNA is DNA from the rectal cancer that is circulating in the blood. The purpose of this study is to understand if the way rectal tumors respond to standard treatment can be associated with varying levels of ctDNA.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Detailed Description
PRIMARY OBJECTIVE:
- To estimate the percentage of participants that achieve complete clinical response.
SECONDARY OBJECTIVES:
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To assess circulating tumor deoxyribonucleic acid (ctDNA) status among participants receiving total neoadjuvant therapy (TNT).
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To assess molecular residual disease (MRD i.e., ctDNA status). III. To assess the rate of transabdominal surgery. IV. To assess the rate pathological complete response after surgery.
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To assess the rate of watch and -wait (W&W) after TNT. VI. To assess disease-free survival (DFS). VII. To assess overall survival (OS).
EXPLORATORY OBJECTIVES:
- To characterize ctDNA clearance or non-clearance patterns during TNT. II. To correlate ctDNA levels with a participant's pathological features. III. To preliminary assess the prognostic performance of ctDNA levels in relation to participant's clinical outcome.
OUTLINE:
Patients undergo collection of blood samples at baseline (before any neoadjuvant therapy), every 2 months while undergoing TNT, and then every 3 months for up to 3 years after completion of TNT. Patients' medical records are also reviewed. Patients may undergo collection of tissue sample if an archival tissue sample is not available.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Observational (biospecimen collection, medical record review) Patients undergo collection of blood samples at baseline (before any neoadjuvant therapy), every 2 months while undergoing TNT, and then every 3 months for up to 3 years after completion of TNT. Patients' medical records are also reviewed. Patients may undergo collection of tissue sample if an archival tissue sample is not available. |
Procedure: Biopsy
Undergo biopsy
Other Names:
Procedure: Biospecimen Collection
Undergo collection of blood and/or tissue samples
Other Names:
Other: Electronic Health Record Review
Medical records are reviewed
|
Outcome Measures
Primary Outcome Measures
- Complete clinical response (cCR) [From time of treatment start up to date of completing total neoadjuvant therapy (TNT), up to 3 months.]
cCR following TNT will be analyzed using the TNT analysis set. Proportions of participants that achieved cCR will be calculated and the exact 95% confidence interval (CI) will be presented.
Secondary Outcome Measures
- Positive circulating tumor deoxyribonucleic acid (ctDNA) [From date of baseline measure of ctDNA (i.e., number of mutant molecules per mL) to date of until the date of first documented progression, up to 3 years.]
The proportion of ctDNA positive participants (at baseline, throughout TNT, and follow-up) and its exact 95% CI will be evaluated using the ctDNA analysis set. Where appropriate, sub-analyses will be conducted using populations that underwent surgery or were monitored using a watch and wait (W&W) strategy.
- Positive ctDNA after completing TNT [From date of baseline measure of ctDNA (i.e., number of mutant molecules per mL) to date of until the date of first documented progression, up to 3 years]
The proportion of ctDNA positive participants (at baseline, throughout TNT, and follow-up) and its exact 95% CI will be evaluated using the ctDNA analysis set. Where appropriate, sub-analyses will be conducted using populations that underwent surgery or were monitored using a W&W strategy.
- Rate of transabdominal surgery [Up to 3 years following completion of TNT]
Will be evaluated using the TNT analysis set. The corresponding exact 95% CI will also be presented.
- Rate of pathological complete response (pCR) [From start of treatment until completion of surgery, up to 3 years.]
Will be evaluated using the TNT analysis set. The corresponding exact 95% CI will also be presented.
- Rate of watch and wait strategy [Up to 3 years following completion of TNT]
Will be evaluated using the TNT analysis set. The corresponding exact 95% CI will also be presented.
- Disease-free survival [Time between the date of surgery (or W&W population, the date of completing TNT) and the date of local or metastatic recurrence or death from any cause, assessed up to 3 years following completion of TNT]
Will be estimated using the Kaplan-Meier method.
- Overall survival [Time between the date of signed consent to the date of death from any cause, assessed up to 3 years following completion of TNT]
Will be estimated using the Kaplan-Meier method.
Other Outcome Measures
- ctDNA status [From date of baseline measure of ctDNA (i.e., number of mutant molecules per mL) to date of until the date of first documented progression, up to 3 years]
positive versus negative results per test results
- Positive ctDNA by clinical characteristics [From date of baseline measure of ctDNA to date of recurrence or death from any cause, assessed up to 3 years following completion of TNT]
association or recurrence on ctDNA test and standard imaging
- Sensitivity [From date of baseline measure of ctDNA to date of recurrence or death from any cause, assessed up to 3 years following completion of TNT]
Sensitivity and specificity will be calculated using complete clinical response (yes versus [vs.] no), or tumor recurrence (yes vs. no) as reference standard.
- Specificity [From date of baseline measure of ctDNA to date of recurrence or death from any cause, assessed up to 3 years following completion of TNT]
Sensitivity and specificity will be calculated using complete clinical response (yes vs. no), or tumor recurrence (yes vs. no) as reference standard.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Participant must provide written informed consent before any study-specific procedures or interventions are performed
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Participants aged >= 18 years
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Pathologically-confirmed stage II or III primary adenocarcinoma of the rectum:
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T3N0M0 - T4bN2M0
Exclusion Criteria:
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Has radiologic evidence of distant metastases at the time of screening/enrollment
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Has received prior treatment for their rectal adenocarcinoma
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Requires or has received blood transfusion within 1 month of study enrollment
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | OHSU Knight Cancer Institute | Portland | Oregon | United States | 97239 |
Sponsors and Collaborators
- OHSU Knight Cancer Institute
- Natera, Inc.
Investigators
- Principal Investigator: Adel Kardosh, M.D.,Ph.D., OHSU Knight Cancer Institute
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- STUDY00022247
- NCI-2021-08733
- STUDY00022247