Watch and Wait in PD-1 Monoclonal Antibody Treated dMMR/MSI-H Distal Rectal Cancer

Launched by SIXTH AFFILIATED HOSPITAL, SUN YAT-SEN UNIVERSITY · Nov 20, 2020

Keywords

ClinConnect Summary

This clinical trial is studying a new approach for treating patients with a specific type of rectal cancer called distal rectal cancer, particularly those whose cancer has shown significant improvement after treatment with a type of immunotherapy known as a PD-1 monoclonal antibody. The aim is to explore whether patients can safely "watch and wait" rather than immediately undergo more invasive treatments like surgery or chemotherapy, which can have serious side effects. This trial is open to adults aged 18 and older who have been diagnosed with rectal adenocarcinoma and have shown a complete response to previous treatments.

To participate, patients need to meet certain criteria, like having a confirmed diagnosis of the specific cancer type and showing no signs of intestinal blockage or previous treatments that could interfere with the study. Those who join the trial can expect regular check-ups to monitor their health and the status of their cancer, while contributing to important research that may help improve future treatment options for rectal cancer. It's important for potential participants to discuss any health issues with their doctor to ensure they meet all the requirements for the trial.

Gender

ALL

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