Watchful waiting for patients with specific rectal cancer after immunotherapy

Watch and Wait in Patients With dMMR/MSI-H Distal Rectal Cancer Accessed Pathological Complete Response After PD-1 Monoclonal Antibody Therapy-an Open Label, Multicenter, Prospective Study (BASKET)

This study tests if carefully monitoring patients with certain types of rectal cancer who responded well to immunotherapy can be a safe alternative to immediate surgery.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 47 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Sixth Affiliated Hospital, Sun Yat-sen University (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT04643041 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and effectiveness of a watch and wait approach for patients with distal rectal cancer who have achieved a pathological complete response after treatment with PD-1 monoclonal antibodies. The focus is on patients with DNA mismatch repair-deficient or microsatellite instability-high rectal cancer, aiming to avoid the complications associated with radical surgery and chemotherapy. By monitoring patients instead of proceeding with immediate surgery, the study seeks to minimize treatment-related side effects while assessing long-term outcomes.

Who should consider this trial

Good fit: Ideal candidates are patients with histologically confirmed rectal adenocarcinoma who have dMMR/MSI-H status and have achieved a pathological complete response after PD-1 monoclonal antibody therapy.

Not a fit: Patients with intestinal obstruction symptoms or those who do not meet the specific immunohistochemical and staging criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could reduce the need for invasive surgeries and improve the quality of life for patients with distal rectal cancer.

How similar studies have performed: While the watch and wait approach has been explored in other cancer types, this specific application in dMMR/MSI-H distal rectal cancer is relatively novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

Preliminary inclusion criteria：

* Histological identified rectal adenocarcinoma,
* Tumor biopsy immunohistochemical (IHC) identified dMMR, including one or more deficient of the MSH1,MSH2,MSH6 and PMS2 protein expression and diagnosed as deficient mismatch repair(dMMR), or next generation sequencing identified (MSI-H)； MRI identified tumor inferior margin lower than peritoneal reflection,
* Clinical staging TxNxM0, with or without positive MRF, with or without positive EMVI,
* Staging method：all patients undergo rectal palpation, high resolution MRI ± transrectal Ultrasound examination，positive perienteric lymph node(LN): short diameter ≥10mm LN or LN with typical metastatic shape and MRI character, clinical data should be re-evaluated and judged by center evaluation group when there are contradictory stagings，distant metastasis were excluded by chest and abdominal enhanced CT and pelvic enhanced MRI,
* No intestinal obstruction symptom，or obstruction relieved after proximal colostomy,
* No rectal surgery history,
* No chemotherapy or radiotherapy history,
* No biopharmaceutical treatment history(such as monoclonal antibody), immunotherapy(such as anti PD-1antibody, anti PD-L1 antibody, anti PD-L2 antibody or anti CTLA-4), or other research drug treatment,
* Endocrinotherapy history restriction:No
* Informed consent assigned, Final inclusion criteria：
* Clinical complete response (cCR)(Chest,abdominal and pelvic enhanced CT or pelvic enhanced MRI or transrectal ultrasound proved)
* Transrectal ultrasound biopsy or endoscopic biopsy proved pathologically complete response (pCR)

Exclusion Criteria:

* Arrhythmia need anti-arrhythmia treatment(except β-blocking agent or Digoxin)，symptomatic coronary heart disease or myocardial ischemia(myocardial infarction within 6 months) or congestive heart-failure (CHF) \> NYHA grade II,
* Severe hypertension not well controlled by drugs,
* HIV infection history or active phase of chronic Hepatitis B or C(high copies of virus DNA),
* Active tuberculosis(TB)，accepting anti-TB treatment or anti-TB treatment within 1 year before trial screen,
* Other active clinical severe infection(NCI-CTC V5.0),
* Outside pelvic distant metastasis evidences,
* Dyscrasia, organ dysfunction,
* Pelvic or abdominal radiotherapy history,
* Multiple CRC or Multi-primary tumors；
* Epilepsy need treatments(Steroid or anti-epilepsy therapy),
* Other malignant tumor history within 5 years,
* Over abuse of drugs, medical and psychological or social conditions that might interfere patients or evaluation of the study results,
* Any active autoimmune disease or autoimmune disease history (including but not restricted：interstitial pneumonia, uveitis,enteritis, hepatitis,hypophysitis, nephritis, hyperthyroidism, hypothyroidism, asthma need bronchodilators),
* Any anti-infection vaccine injection 4 weeks before inclusion ,
* Long-term exposure to immune-suppressor, combination of systemic or topical use of corticosteroids (dose\>10mg/day prednisolone or equivalent hormone)；
* Known or suspicious allergy to any study related drugs,
* Any unstable state might cause damage to the safety and compliance of patients,
* Pregnant or breast feeding women who has ability to have children while without contraception,
* Refuse to sign informed consent

Where this trial is running

Guangzhou, Guangdong

• Sun Yatsen University — Guangzhou, Guangdong, China (Recruiting)

Study contacts

• Study coordinator: Jun Huang, MD

Conditions Rectal Cancer; PD-1 monoclonal antibody; watch and wait; dMMR/MSI-H; distal rectal cancer