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

NCT05669092 | Unknown Phase 3

• 1 other identifier: CARTOnG 2201
• Study Type: interventional
• Target: 174
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Toripalimab; Radiation

Outcome Measures

Primary Outcomes (1)

• complete response (CR) rate.

  cCR ≥ 1 year.

  The status of cCR will be evaluated after the completion of neoadjuvant therapy.

Secondary Outcomes (6)

• adverse effects rate.

  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

  From date of randomization until the date of death from any cause, assessed up to 10 years

• 3 year local recurrence free survival rate

  From date of randomization until the date of first documented pelvic failure, assessed up to 36 months. ]

• 3 year disease free survival rate

  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

  From date of randomization until the date of death from any cause, assessed up to 36 months.

Study Arms (4)

ARM A: dMMR/MSI-H patients

EXPERIMENTAL

patients will receive 12 cycles of PD-1 antibody

Drug: Toripalimab

ARM B: dMMR/MSI-H patients

EXPERIMENTAL

patients will receive 5\*5Gy short-course radiotherapy, followed by 12 cycles of PD-1 antibody

Drug: Toripalimab; Radiation: SCRT

ARM C: pMMR/MSS patients

EXPERIMENTAL

patients will receive CRT followed by 6 cycles of XELIRI

Radiation: CRT; Drug: XELIRI

ARM D: pMMR/MSS patients

EXPERIMENTAL

patients will receive CRT followed by 12 cycles of FOLFRINOX

Radiation: CRT; Drug: FOLFRINOX

Interventions

Toripalimab DRUG

3mg/Kg iv d1q2w

Also known as: PD-1inhibitor

ARM A: dMMR/MSI-H patients; ARM B: dMMR/MSI-H patients

CRT RADIATION

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

Also known as: LCRT

ARM C: pMMR/MSS patients; ARM D: pMMR/MSS patients

SCRT RADIATION

25Gy/5fx

Also known as: short-course radiotherapy

ARM B: dMMR/MSI-H patients

XELIRI DRUG

Capecitabine: 1000mg/m2 bid d1-14 Irinotecan: 200mg/m2 ivgtt d1 q3w

Also known as: Capecitabine and Irinotecan

ARM C: pMMR/MSS patients

FOLFRINOX DRUG

Irinotecan: 150mg/m2 ivgtt d1 (double locus mutation downregulated to 120mg/m2) Oxaliplatin: 85mg/m2 ivgtt d1 5-FU: 2400mg/m2 ivgtt 46h q2w

Also known as: Irinotecan,Oxaliplatin and 5-FU

ARM D: pMMR/MSS patients

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• pregnant or breastfeeding women；
• 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；
• 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；
• persons requiring immunosuppressive therapy for organ transplantation；
• Persons with severe uncontrolled recurrent infections, or other severe uncontrolled concomitant diseases；
• 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；
• Known to have dihydropyrimidine dehydrogenase (DPD) deficiency；
• allergic to any investigational drug component.

Sponsors & Collaborators

• Zhejiang Cancer Hospital: lead

Study Sites (1)

Zhengjiang Cancer Hospital

Hangzhou, Zhejiang, China

RECRUITING

Related Publications (1)

• Huang CY, Bai MH, Shen JW, Sun QQ, Feng YR, Chen QP, Mao W, Ju HX, Zhu J. Anus preservation in low rectal adenocarcinoma based on MMR/MSI status (APRAM): a study protocol for a randomised, controlled, open-label, multicentre phase III trial. BMC Cancer. 2024 Jan 10;24(1):57. doi: 10.1186/s12885-024-11829-2.

  PMID: 38200410 DERIVED

MeSH Terms

Interventions

toripalimab; Capecitabine; Irinotecan; Oxaliplatin; Fluorouracil

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Camptothecin; Alkaloids; Coordination Complexes; Organic Chemicals

Central Study Contacts

JI ZHU

CONTACT

13501978674; zhuji@zjcc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: professor

Study Record Dates

• First Submitted: November 28, 2022
• First Posted: December 30, 2022
• Study Start: November 1, 2022
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: December 30, 2022

Record last verified: 2022-12

Locations

CN (1)