Immunotherapy, Organ Preservation, Radiotherapy, Rectal Cancer
Conditions
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.
Interventions
DRUGChemotherapy
CAPOX (6 cycles): Oxaliplatin(130mg/m2) on day 1 of each cylce and Capecitabine: Dose of 2000mg/m2,14 days, q3w
DRUGImmunotherapy
Camrelizumab (6 cycles): 200mg on day 1 of each cycle, q3w
RADIATIONIMRT
Radiotherapy (5 Gy x 5 fractions)
Sponsors
Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Patients who personally provided written consent for participation in the study 2. 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 3. 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 4. Patients with the ECOG performance status of 0 or 1 at the time of enrollment 5. 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 6. 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 7. 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
1. Patients with recurrent rectal cancer or a history of pelvic radiation 2. Patients with a history of inflammatory bowel disease 3. Patients with a history of pneumonitis or interstitial lung disease 4. Patients with concurrent autoimmune disease or a history of chronic or recurrent autoimmune disease 5. Patients requiring treatment with systemic corticosteroids or immunosuppressants or who have received these treatments within 14 days before enrollment in the study 6. Patients with a history of thyroid dysfunction 7. Patients with a history or finding of cardiovascular risk 8. Patients who are positive for any of the following: HIV1 antibody, HIV2 antibody, HTLV1 antibody 9. Patients who are pregnant or lactating or who may be pregnant 10. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical complete response rate (cCR) | 8 (+/-4 ) weeks | Proportion of patients who achieve a clinical complete response following treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Local regrowth rate | 2 year | Presence of adenocarcinoma within the rectal wall or within the mesorectum confirmed by pathology |
| Disease free survival (DFS) | 5 year | Five years disease-free survival of this group of patients |
| Overall survival (OS) | 5 year | Fives years overall survival of this group of patients |
| Incidence of adverse events (AEs) | 1 year | 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). |
Countries
China
Outcome results
None listed