Rectal CancerNCT04670588
Response Assessment by Circulating Tumor DNA in Patients With Locally Advanced Rectal Cancer
An observational study of Rectal Cancer, run by Medical College of Wisconsin at 1 site in United States.
Trial summary
This is a single-arm observational study to determine the feasibility of assessing tumor response utilizing Circulating tumor DNA (ctDNA) in patients of with locally advanced rectal cancer (LARC) undergoing standard-of-care total neoadjuvant therapy (TNT) consisting of systemic chemotherapy (modified FOLFOX or… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Rectal Cancer
- What is being tested?
- Circulating tumor DNA(ctDNA) level measurement
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 31 Mar 2021to 1 Jun 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with locally advanced rectal cancer (LARC) undergoing total neoadjuvant therapy (TNT).
Who may be able to join
- Patients with histologically or cytologically documented rectal cancer eligible for total neoadjuvant therapy (TNT).
- Male or female subjects ≥18 years old.
- Rectal tumor biopsy is available for SignateraTM assay development for ctDNA measurement.
- Patients must be able to understand the informed consent form and provide written consent.
Who cannot join
- Patients without available rectal biopsy tissue for SignateraTM assay development.
- Patients with rectal cancer not eligible to receive standard-of-care TNT for any reason.
- Patients with undetectable ctDNA level in the baseline blood sample.
- Patients without trackable mutation in the rectal tumor.
Trial locations and contacts
1 site in 1 country.
United States1 site
Froedtert & the Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
About this study
Official title: A Prospective Observational Study to Determine the Feasibility of Tumor Response Assessment by Circulating Tumor DNA in Patients With Locally Advanced Rectal Cancer Undergoing Total Neoadjuvant Therapy
This is a single-arm observational study to determine the feasibility of assessing tumor response utilizing Circulating tumor DNA (ctDNA) in patients of with locally advanced rectal cancer (LARC) undergoing standard-of-care total neoadjuvant therapy (TNT) consisting of systemic chemotherapy (modified FOLFOX or modified FOLFIRINOX) followed by concurrent chemoradiation (50.4 Gy over approximately six weeks with concurrent radiosensitizing dose of capecitabine/5-fluorouracil).
Read the detailed description
In this observational study, patients with LARC who are selected for the standard-of-care TNT will be enrolled. After obtaining informed consent, a venous blood sample and the archival tissue block from the initial diagnostic rectal tumor biopsy will be sent to the Natera laboratory for designing patient-specific ctDNA assay, which will be used to measure ctDNA levels in the peripheral venous blood samples at various time points coinciding with the standard studies to assess tumor response. The blood sample needed for designing the assay and measuring the baseline ctDNA level will be obtained within four weeks before neoadjuvant chemotherapy begins. Subsequently, for patients undergoing 16 weeks of neoadjuvant chemotherapy, blood samples will be obtained for ctDNA level measurement at three time points ( after eight weeks/4 cycles of neoadjuvant chemotherapy within +/- 5 days of the magnetic resonance imaging (MRI) study, after 16 weeks/8 cycles of neoadjuvant chemotherapy within +/- 5 days of the MRI study, and one to 14 days before surgery ). For patients who receive eight weeks of neoadjuvant chemotherapy, two blood samples will be obtained for subsequent ctDNA measurements (after eight weeks/4 cycles of neoadjuvant chemotherapy within +/- 5 days of the MRI study, and one to 14 days before surgery). All patients may also choose to undergo additional serial ctDNA level measurements for surveillance after the surgery every three to four months for two years (optional).
Tumor response rate assessed by ctDNA (defined as reduction of ctDNA level at least by 90% compared to the baseline level) will be compared with the response rate assessed by the standard method (proctoscopic examination, pelvic MRI, etc.) to explore if a significant correlation exists between these two response assessment methods. If preliminary data support the hypothesis that peripheral blood ctDNA can be utilized for tumor response assessment in this scenario, a larger study will be conducted to validate this method. Once validated, ctDNA measurement can potentially replace expensive, uncomfortable, and time-consuming methods of tumor response assessment like MRI.
- Conditions
- Rectal Cancer
- Being tested
- Circulating tumor DNA(ctDNA) level measurement
- Keywords
- Locally advanced rectal cancer
- Medical subject headings
- Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Circulating tumor DNA(ctDNA) level measurementDiagnostic test
The ctDNA level will be measured using the Signatera platform developed by Natera, Inc. Signatera is a patient-specific, tumor informed custom-built ctDNA monitoring assay.
| Study group | Role | What they receive |
|---|---|---|
| Locally advanced rectal cancer patients | Patients with LARC undergoing TNT. Receives: Diagnostic Test: Circulating tumor DNA(ctDNA) level measurement |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean serum ctDNA concentration
This measure is the concentration of ctDNA in plasma expressed as mean tumor molecules (MTM)/ml at specific time points.
Measured: Baseline, 8 weeks, 16 weeks, around 24 weeks before rectal surgery.
Secondary outcomes (2)
Response based on serum ctDNA level (change from baseline)
This measure is the number of subjects achieving a reduction of ctDNA level (mean tumor molecules[MTM]/ml) by > 90% compared to the baseline.
Measured: Baseline, 8 weeks, 16 weeks, around 24 weeks before rectal surgery
Response based on standard clinical assessments
This measure is the number of subjects achieving a clinical change of tumor size based on standard clinical assessments. Response will be a determined as a subjective measure by experienced clinicians using any combination of pelvic MRI, visual proctoscopic examination, sigmoidoscopy, and/or endoscopic ultrasound.
Measured: Baseline, 8 weeks, 16 weeks, around 24 weeks before rectal surgery.]
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2020
- Study start31 Mar 2021
- Primary completion1 Jun 2022
- Study completion1 Jun 2022
Why it stopped: No accrual.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Rectal CancerStudies of the same condition, open and under way.
- More trials run by Medical College of WisconsinThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical College of Wisconsin
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Sakti Chakrabarti, MD, Medical College of Wisconsin
- Investigators
- Sakti Chakrabarti, MD, Principal investigator, Medical College of Wisconsin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04670588
- Sponsor's protocol ID
- PRO00039395
- Status last verified
- Jul 2022
- First submitted
- 10 Dec 2020
- Last updated
- 18 Jul 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Publications
Reinert T, Henriksen TV, Christensen E, Sharma S, Salari R, Sethi H, Knudsen M, Nordentoft I, Wu HT, Tin AS, Heilskov Rasmussen M, Vang S, Shchegrova S, Frydendahl Boll Johansen A, Srinivasan R, Assaf Z, Balcioglu M, Olson A, Dashner S, Hafez D, Navarro S, Goel S, Rabinowitz M, Billings P, Sigurjonsson S, Dyrskjot L, Swenerton R, Aleshin A, Laurberg S, Husted Madsen A, Kannerup AS, Stribolt K, Palmelund Krag S, Iversen LH, Gotschalck Sunesen K, Lin CJ, Zimmermann BG, Lindbjerg Andersen C. Analysis of Plasma Cell-Free DNA by Ultradeep Sequencing in Patients With Stages I to III Colorectal Cancer. JAMA Oncol. 2019 Aug 1;5(8):1124-1131. doi: 10.1001/jamaoncol.2019.0528.
PubMed 31070691
Study at a glance
From the registry record, last updated by the sponsor on 18 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Prospective Observational Study to Determine the Feasibility of Tumor Response Assessment by Circulating Tumor DNA in Patients With Locally Advanced Rectal Cancer Undergoing Total Neoadjuvant Therapy
- ClinicalTrials.gov ID
- NCT04670588
- Acronym / sponsor ID
- PRO00039395
- Conditions
- Rectal Cancer
- Keywords
- Locally advanced rectal cancer
- Study type
- Observational
- Recruitment status
- WithdrawnReason stopped: No accrual.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Medical College of WisconsinUniversity, hospital or other
- Study start
- 31 Mar 2021 (actual)
- Primary completion
- 1 Jun 2022 (actual)
- Study completion
- 1 Jun 2022 (actual)
- First posted
- 17 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a single-arm observational study to determine the feasibility of assessing tumor response utilizing Circulating tumor DNA (ctDNA) in patients of with locally advanced rectal cancer (LARC) undergoing standard-of-care total neoadjuvant therapy (TNT) consisting of systemic chemotherapy (modified FOLFOX or modified FOLFIRINOX) followed by concurrent chemoradiation (50.4 Gy over approximately six weeks with concurrent radiosensitizing dose of capecitabine/5-fluorouracil).
Detailed description
In this observational study, patients with LARC who are selected for the standard-of-care TNT will be enrolled. After obtaining informed consent, a venous blood sample and the archival tissue block from the initial diagnostic rectal tumor biopsy will be sent to the Natera laboratory for designing patient-specific ctDNA assay, which will be used to measure ctDNA levels in the peripheral venous blood samples at various time points coinciding with the standard studies to assess tumor response. The blood sample needed for designing the assay and measuring the baseline ctDNA level will be obtained within four weeks before neoadjuvant chemotherapy begins. Subsequently, for patients undergoing 16 weeks of neoadjuvant chemotherapy, blood samples will be obtained for ctDNA level measurement at three time points ( after eight weeks/4 cycles of neoadjuvant chemotherapy within +/- 5 days of the magnetic resonance imaging (MRI) study, after 16 weeks/8 cycles of neoadjuvant chemotherapy within +/- 5 days of the MRI study, and one to 14 days before surgery ). For patients who receive eight weeks of neoadjuvant chemotherapy, two blood samples will be obtained for subsequent ctDNA measurements (after eight weeks/4 cycles of neoadjuvant chemotherapy within +/- 5 days of the MRI study, and one to 14 days before surgery). All patients may also choose to undergo additional serial ctDNA level measurements for surveillance after the surgery every three to four months for two years (optional).
Tumor response rate assessed by ctDNA (defined as reduction of ctDNA level at least by 90% compared to the baseline level) will be compared with the response rate assessed by the standard method (proctoscopic examination, pelvic MRI, etc.) to explore if a significant correlation exists between these two response assessment methods. If preliminary data support the hypothesis that peripheral blood ctDNA can be utilized for tumor response assessment in this scenario, a larger study will be conducted to validate this method. Once validated, ctDNA measurement can potentially replace expensive, uncomfortable, and time-consuming methods of tumor response assessment like MRI.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Locally advanced rectal cancer patients | – | Diagnostic Test: Circulating tumor DNA(ctDNA) level measurementPatients with LARC undergoing TNT. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with locally advanced rectal cancer (LARC) undergoing total neoadjuvant therapy (TNT).
Key inclusion criteria (4 listed)
- Patients with histologically or cytologically documented rectal cancer eligible for total neoadjuvant therapy (TNT).
- Male or female subjects ≥18 years old.
- Rectal tumor biopsy is available for SignateraTM assay development for ctDNA measurement.
- Patients must be able to understand the informed consent form and provide written consent.
Key exclusion criteria (4 listed)
- Patients without available rectal biopsy tissue for SignateraTM assay development.
- Patients with rectal cancer not eligible to receive standard-of-care TNT for any reason.
- Patients with undetectable ctDNA level in the baseline blood sample.
- Patients without trackable mutation in the rectal tumor.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Circulating tumor DNA(ctDNA) level measurementThe ctDNA level will be measured using the Signatera platform developed by Natera, Inc. Signatera is a patient-specific, tumor informed custom-built ctDNA monitoring assay. | Diagnostic test | Locally advanced rectal cancer patients |
Primary outcome
Mean serum ctDNA concentration
Time frame: Baseline, 8 weeks, 16 weeks, around 24 weeks before rectal surgery.
This measure is the concentration of ctDNA in plasma expressed as mean tumor molecules (MTM)/ml at specific time points.
2 secondary outcomes
Response based on serum ctDNA level (change from baseline)
Time frame: Baseline, 8 weeks, 16 weeks, around 24 weeks before rectal surgery
Response based on standard clinical assessments
Time frame: Baseline, 8 weeks, 16 weeks, around 24 weeks before rectal surgery.]
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jul 2022.
- Results publication: PubMed 31070691Reinert T, Henriksen TV, Christensen E, Sharma S, Salari R, Sethi H, Knudsen M, Nordentoft I, Wu HT, Tin AS, Heilskov Rasmussen M, Vang S, Shchegrova S, Frydendahl Boll Johansen A, Srinivasan R, Assaf Z, Balcioglu M, Olson A, Dashner S, Hafez D, Navarro S, Goel S, Rabinowitz M, Billings P, Sigurjonsson S, Dyrskjot L, Swenerton R, Aleshin A, Laurberg S, Husted Madsen A, Kannerup AS, Stribolt K, Palmelund Krag S, Iversen LH, Gotschalck Sunesen K, Lin CJ, Zimmermann BG, Lindbjerg Andersen C. Analysis of Plasma Cell-Free DNA by Ultradeep Sequencing in Patients With Stages I to III Colorectal Cancer. JAMA Oncol. 2019 Aug 1;5(8):1124-1131. doi: 10.1001/jamaoncol.2019.0528.
- Manufacturer's site posting four scientific abstracts.Link provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sakti Chakrabarti, MD principal investigator
Medical College of Wisconsin
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Rectal Cancer, run by Medical College of Wisconsin at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 18 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean serum ctDNA concentration (time frame: Baseline, 8 weeks, 16 weeks, around 24 weeks before rectal surgery.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04670588, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jul 2022.