Radiotherapy With Neoadjuvant Chemotherapy and Immunotherapy in Rectal Cancer

Study Overview
=================
Brief Summary
-----------------
This is a open-label, single-arm study to investigate the safety and efficacy of Total neoadjuvant chemotherapy with camrelizumab, an anti-PD-1 antibody drug following short course radiotherapy in patients with rectal cancer.

Detailed Description
-----------------
Patients with rectal cancer are assigned to receive preoperative 5 × 5 Gy irradiation over 5 days with total neoadjuvant chemotherapy and camrelizumab, an anti-PD-1 antibody drug. The Primary Objective is to assess clinical complete response of an organ preservation approach and the secondary objective to assess safety in all enrolled patients, local regrowth rate and other cancer specific outcomes (metastasis-free survival, colostomy-free survival and overall survival), longitudinal health-related quality of life of this organ preservation approach.

Official Title
-----------------
Short Course Radiotherapy With Total Neoadjuvant Chemotherapy and Immunotherapy in Rectal Cancer

Conditions
-----------------
Rectal Cancer, Radiotherapy, Immunotherapy, Organ Preservation

Intervention / Treatment
-----------------
* Drug: Chemotherapy
* Drug: Immunotherapy
* Radiation: IMRT


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients who personally provided written consent for participation in the study Treatment-naive patients with rectal cancer, in whom the inferior margin of the tumor is at a distance of 10 cm or less from the AV before CRT Histologically confirmed adenocarcinoma of rectum (non-metastatic, >T2N0 or low T2N0 rectal cancer) not eligible for up-front organ preservation surgery as deemed by multidisciplinary evaluation Patients with the ECOG performance status of 0 or 1 at the time of enrollment Women of childbearing potential who consent to practicing contraception during the period from giving informed consent to at least 23 weeks after the last dose of therapy Male patients who consent to practicing contraception during the period from giving informed consent to at least 31 weeks after the last dose of the study drug Patients must have acceptable organ and marrow function as defined below: Absolute neutrophil count (ANC) >1,500/uL Hg > 8.0 g/dL; if blood transfusion is performed for achieving adequate hemoglobin level, the level should stay above goal for at least 1 week after transfusion Platelets >100,000/uL Total bilirubin <1.5X normal institutional limits aspartate aminotransferase (AST) (SGOT) / alanine aminotransferase (ALT)(SGPT) < 3X upper limit of normal Creatinine <1.5X upper limit of normal or creatinine clearance (CrCL)>50 by Cockcroft-Gault Exclusion Criteria: Patients with recurrent rectal cancer or a history of pelvic radiation Patients with a history of inflammatory bowel disease Patients with a history of pneumonitis or interstitial lung disease Patients with concurrent autoimmune disease or a history of chronic or recurrent autoimmune disease Patients requiring treatment with systemic corticosteroids or immunosuppressants or who have received these treatments within 14 days before enrollment in the study Patients with a history of thyroid dysfunction Patients with a history or finding of cardiovascular risk Patients who are positive for any of the following: HIV1 antibody, HIV2 antibody, HTLV1 antibody Patients who are pregnant or lactating or who may be pregnant Patients with significant unstable mental diseases or other medical diseases that may interfere with the safety of the subjects, obtaining informed consent, or compliance with the procedures for the clinical study

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: radiotherapy, chemotherapy and PD1 inhibitor<br>Treatment will comprise 5 daily fractions of radiotherapy at 5 Gy per fraction followed by chemotherapy and immunotherapy. Those who achieve a clinical complete response will be considered for organ preservation approach. All other patients will receive standard surgery. | Drug: Chemotherapy<br>* CAPOX (6 cycles): Oxaliplatin(130mg/m2) on day 1 of each cylce and Capecitabine: Dose of 2000mg/m2,14 days, q3w<br>Drug: Immunotherapy<br>* Camrelizumab (6 cycles): 200mg on day 1 of each cycle, q3w<br>Radiation: IMRT<br>* Radiotherapy (5 Gy x 5 fractions)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical complete response rate (cCR) | Proportion of patients who achieve a clinical complete response following treatment | 8 (+/-4 ) weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Local regrowth rate | Presence of adenocarcinoma within the rectal wall or within the mesorectum confirmed by pathology | 2 year | 
| Disease free survival (DFS) | Five years disease-free survival of this group of patients | 5 year | 
| Overall survival (OS) | Fives years overall survival of this group of patients | 5 year | 
| Incidence of adverse events (AEs) | Incidence of adverse events will be assessed according to the latest Clavien- Dindo Classification of surgical complications and Common Terminology Criteria of Adverse Events (CTCAE). | 1 year |