A Phase III Trial of Anus-preservation in Low Rectal Adenocarcinoma Based on MMR/MSI Status

December 29, 2022 updated by: Ji Zhu, Zhejiang Cancer Hospital

A Randomized, Controlled, Open-label, Multicenter, Phase III Trial of Anus-preservation in Low Rectal Adenocarcinoma Based on MMR/MSI Status(APRAM)

pMMR/MSS and 32 dMMR/MSI-H patientspatients were planned to be enrolled. Patients with dMMR/MSI-H will be randomly assigned to the immunotherapy arm or short-course radiotherapy sequential immunotherapy arm; pMMR/MSS patients will receive capecitabine-irinotecan based concurrent radiotherapy before being randomly assigned to the XELIRI or FOLFRINOX arm.

The rate of complete response (sustained cCR for ≥ 1 year), long-term prognosis and adverse effects will be analyzed.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
174

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • China
    • Zhejiang
      • Hangzhou, Zhejiang, China
        • Recruiting
        • Zhengjiang Cancer Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. pathological confirmed adenocarcinoma；
  2. clinical stage T2-4 and/or N+，Not suitable for initial local excision to achieve radical treatment；
  3. the distance from anal verge less than ≤ 5cm，or surgical evaluation concludes that direct surgical anal preservation is not possible without distance metastases；
  4. age 18-70 years old, female and male；
  5. Strong desire for anal preservation and ability to be closely monitored for at least 2 years after chemoradiotherapywith good compliance；
  6. without distant metastases；
  7. ECOG Performance status 0-1；
  8. Detection of UGT1A1*6 and *28 gene status (for pMMR patients)；
  9. Sufficient bone marrow reserve and physical capacity to receive consolidation chemotherapy after chemoradiotherapy (for pMMR patients)；
  10. with good compliance；
  11. signed the inform consen.

Exclusion Criteria:

  1. pregnant or breastfeeding women；
  2. Persons with a history of uncontrolled epilepsy, central nervous system disorders, or psychiatric disorders whose clinical severity, as judged by the investigator, may prevent the signing of informed consent or affect the patient's compliance with oral medications；
  3. Difficult to achieve complete remission at the available level of evidence, such as: tumor largest diameter >10 cm; largest diameter of lateral lymph nodes >2 cm; baseline CEA >= 100; biopsy pathology with an indolent cell carcinoma component; tumor of circumferential narrowing type on anal finger examination, with inclusion decided by the judgment of the evaluation team if necessary；
  4. Clinically significant (i.e., active) heart disease, such as symptomatic coronary artery disease, New York Heart Association (NYHA) class II or worse congestive heart failure or severe arrhythmias requiring pharmacological intervention, or a history of myocardial infarction within the last 12 months；
  5. persons requiring immunosuppressive therapy for organ transplantation；
  6. Persons with severe uncontrolled recurrent infections, or other severe uncontrolled concomitant diseases；
  7. Subjects with baseline routine blood and biochemical indicators do not meet the following criteria: hemoglobin ≥ 90g/L; absolute neutrophil count (ANC) ≥ 1.5×109/L; platelets ≥ 100×109/L; ALT, AST ≤ 2.5 times the upper limit of normal; ALP ≤ 2.5 times the upper limit of normal; serum total bilirubin < 1.5 times the upper limit of normal; serum creatinine < 1 times the upper limit of normal limit; serum albumin ≥30g/L；
  8. Known to have dihydropyrimidine dehydrogenase (DPD) deficiency；
  9. allergic to any investigational drug component.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: ARM A: dMMR/MSI-H patients
patients will receive 12 cycles of PD-1 antibody
Drug: Toripalimab
3mg/Kg iv d1q2w
Other Names:
  • PD-1inhibitor
Experimental: ARM B: dMMR/MSI-H patients
patients will receive 5*5Gy short-course radiotherapy, followed by 12 cycles of PD-1 antibody
Drug: Toripalimab
3mg/Kg iv d1q2w
Other Names:
  • PD-1inhibitor
Radiation: SCRT
25Gy/5fx
Other Names:
  • short-course radiotherapy
Experimental: ARM C: pMMR/MSS patients
patients will receive CRT followed by 6 cycles of XELIRI
Radiation: CRT
IMRT 50Gy/25fx 625mg/m2 bid d1-5 qw Irinotecan:1、Full wild (GG+6/6): 80mg/m2/week for 5 times 2、Single site mutation (GG+6/7 or GA+6/6): 65mg/m2/week for 5 times 3、Double locus mutation (GG+7/7 or AA+6/6 or GA+6/7): 50mg/m2/week for the 1st, 2nd, 4th and 5th week for 4 times
Other Names:
  • LCRT
Drug: XELIRI
Capecitabine: 1000mg/m2 bid d1-14 Irinotecan: 200mg/m2 ivgtt d1 q3w
Other Names:
  • Capecitabine and Irinotecan
Experimental: ARM D: pMMR/MSS patients
patients will receive CRT followed by 12 cycles of FOLFRINOX
Radiation: CRT
IMRT 50Gy/25fx 625mg/m2 bid d1-5 qw Irinotecan:1、Full wild (GG+6/6): 80mg/m2/week for 5 times 2、Single site mutation (GG+6/7 or GA+6/6): 65mg/m2/week for 5 times 3、Double locus mutation (GG+7/7 or AA+6/6 or GA+6/7): 50mg/m2/week for the 1st, 2nd, 4th and 5th week for 4 times
Other Names:
  • LCRT
Drug: FOLFRINOX
Irinotecan: 150mg/m2 ivgtt d1 (double locus mutation downregulated to 120mg/m2) Oxaliplatin: 85mg/m2 ivgtt d1 5-FU: 2400mg/m2 ivgtt 46h q2w
Other Names:
  • Irinotecan,Oxaliplatin and 5-FU

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
complete response (CR) rate.
Time Frame: The status of cCR will be evaluated after the completion of neoadjuvant therapy.
cCR ≥ 1 year.
The status of cCR will be evaluated after the completion of neoadjuvant therapy.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
adverse effects rate.
Time Frame: From date of randomization until the date of death from any cause, assessed up to 5 years ] Rate of chemotherapy, radiotherapy and immunotherapy related adverse events.
CTC 4.0 standard.
From date of randomization until the date of death from any cause, assessed up to 5 years ] Rate of chemotherapy, radiotherapy and immunotherapy related adverse events.
QoL
Time Frame: From date of randomization until the date of death from any cause, assessed up to 10 years
Quality of life will be evaluated using EORTC QLQ-C30 score
From date of randomization until the date of death from any cause, assessed up to 10 years
3 year local recurrence free survival rate
Time Frame: From date of randomization until the date of first documented pelvic failure, assessed up to 36 months. ]
Rate of 3 year local recurrence free survival
From date of randomization until the date of first documented pelvic failure, assessed up to 36 months. ]
3 year disease free survival rate
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months. ]
Rate of 3 year disease free survival
From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 36 months. ]
3 year overall survival rate
Time Frame: From date of randomization until the date of death from any cause, assessed up to 36 months.
Rate of 3 year overall survival
From date of randomization until the date of death from any cause, assessed up to 36 months.
Organ preservation
Time Frame: From date of randomization until the date of surgery
TME-free survival
From date of randomization until the date of surgery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Zhejiang Cancer Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 1, 2022

Primary Completion (Anticipated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2025

Study Completion (Anticipated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 28, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 29, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 30, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 30, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 29, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CARTOnG 2201

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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