Anus-preserving treatment for low rectal cancer based on genetic status

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

This study is testing different treatments for low rectal cancer based on patients' genetic makeup to see which options work best and have the fewest side effects.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 174 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Zhejiang Cancer Hospital (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy
• Locations: 1 site (Hangzhou, Zhejiang)
• Trial ID: NCT05669092 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate anus-preserving treatment options for patients with low rectal adenocarcinoma based on their MMR/MSI status. Patients with dMMR/MSI-H will be randomly assigned to receive either immunotherapy or a combination of short-course radiotherapy followed by immunotherapy. Those with pMMR/MSS will undergo concurrent radiotherapy with capecitabine-irinotecan before being randomized to either the XELIRI or FOLFRINOX treatment arms. The study will analyze the rate of complete response, long-term prognosis, and adverse effects associated with these treatment approaches.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18-70 with confirmed low rectal adenocarcinoma who are not suitable for initial local excision and have a strong desire for anal preservation.

Not a fit: Patients with distant metastases or those who are pregnant or breastfeeding may not benefit from this study.

Why it matters

Potential benefit: If successful, this trial could provide a new, effective treatment option that preserves anal function for patients with low rectal cancer.

How similar studies have performed: Other studies have shown promise in similar approaches, particularly in the use of immunotherapy for rectal cancer, but this specific trial's methodology is novel.

Eligibility criteria

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.

Where this trial is running

Hangzhou, Zhejiang

• Zhengjiang Cancer Hospital — Hangzhou, Zhejiang, China (Recruiting)

Study contacts

• Study coordinator: Ji Zhu

Conditions Toripalimab; Radiation