Total Neoadjuvant Treatment Plus SHR1210 for High-risk Rectal Cancer and Biomarker Screening Base on Neoantigen

NCT04340401 | Unknown Phase 2

• 1 other identifier: PKUCH-R04
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

This study is designed to test the efficacy and safety of Total Neoadjuvant Treatment plus SHR1210（an anti-PD-1 Inhibitor) for High-risk locally advanced Rectal Cancer, Meanwhile, screening effective Biomarker base on neoantigen.

Conditions

Rectal Cancer

Keywords

High-risk locally advanced Rectal cancer; SHR-1210; Total Neoadjuvant chmoradiation Treatment; pCR rate

Outcome Measures

Primary Outcomes (1)

• pathologic complete response rate(pCR rate)

  The number of patients with pCR divided by the total number of patients

  1 month after surgery

Secondary Outcomes (5)

• Toxicity of TNT+SHR-1210

  90 days after neoadjuvant treatment

• Change of TCR repertoire

  1 week before surgery

• Disease-free survival (DFS)

  3 years

• Surgical complication rate

  30 days after surgery

• Major adverse events

  90 days after the last use of SHR-1210

Study Arms (1)

TNT+SHR1210

EXPERIMENTAL

Patients with high-risk locally advanced rectal cancer will receive chemotherapy and SHR-1210 before chemoradiaton, after chemoradiaton, patient will receive consolidation chemotherapy. This arm is called Total Neoadjuvant Treatment (TNT) plus SHR-1210. The neoadjuvant chemotherapy regimen is designed as 3 cycles of CapeOX ( Capecitabine + Oxaliplatin ) plus SHR-1210 over a period of approximately 8 weeks. Tumor response will be evaluated after chemotherapy. Then patients will undergo 22f-IMRT (Intensity modulated radiotherapy) with capecitabine. Patients will receive two more cycles of consolidation CapeOX if tolerable when there was no progressed disease in induction CapeOX. Finally, patients will receive TME (Total mesorectal excision) following TNT+SHR1210 if no metastasis occurs.

Drug: SHR-1210; Drug: Oxaliplatin; Drug: Capecitabine; Radiation: Intensity modulated radiotherapy; Procedure: Total mesorectal excision

Interventions

SHR-1210 DRUG

Patients will receive 3 cycles induction CapeOX and SHR-1210

Also known as: Camrelizumab

TNT+SHR1210

Oxaliplatin DRUG

CapeOX is a combination chemotherapy regimen with OXA and CAPE, patients with high-risk rectal cancer will receive 3 cycles induction CapeOX and SHR-1210, intensity modulated radiotherapy with concurrent capecitabine and 2 cycles consolidation CapeOX and total mesorectal excision.

Also known as: OXA

TNT+SHR1210

Capecitabine DRUG

CapeOX is a combination chemotherapy regimen with OXA and CAPE, patients with high-risk rectal cancer will receive 3 cycles induction CapeOX and SHR-1210, intensity modulated radiotherapy with concurrent capecitabine and 2 cycles consolidation CapeOX and total mesorectal excision.

Also known as: CAPE

TNT+SHR1210

Intensity modulated radiotherapy RADIATION

patients will receive intensity modulated radiotherapy with capecitabine

Also known as: IMRT

TNT+SHR1210

Total mesorectal excision PROCEDURE

Patients will receive TME (Total mesorectal excision) following TNT+SHR1210 if no metastasis occurs.

Also known as: TME

TNT+SHR1210

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years and ≤70 years.
• ECOG Performance status 0-1.
• Histologically confirmed diagnosis of adenocarcinoma of the rectum.
• The distance from down verge of tumor to anal-rectal junction (ARJ) ≤8cm, or ≤12 cm based on sigmoidoscopy.
• Clinical Stage T3c, T3d, T4a or T4b, or EMVI (+) or mrN2 or MRF (+) based on MRI.
• No evidence of distant metastases.
• No prior pelvic radiation therapy.
• No prior chemotherapy or surgery for rectal cancer.
• No active infections requiring systemic antibiotic treatment.
• No systemic infection requiring antibiotic treatment.
• No immune system disease.
• ANC \> 1.5 cells/mm3, HGB \> 9.0 g/dL, PLT \> 100,000/mm3, total bilirubin≤ 1.5×ULN, AST≤ 2.5×ULN, ALT ≤ 2.5×ULN.
• Serum creatinine is within 1.5 times the physiological range， creatinine clearance rate≥50 ml/min
• Patients with controllable hypertension were included.
• Patients who did not receive anticoagulant therapy: INR, aPTT is required to be within the 1.5 times the physiological range;Patients who receive anticoagulant therapy: INR, aPTT is required to be within the physiological range.

You may not qualify if:

• Recurrent rectal cancer.
• Anticipated unresectable tumor after neoadjuvant treatment.
• Patients with a history of a prior malignancy within the past 5 years, except for adequately treated basal cell or squamous cell skin cancer.
• Patients with a history of any arterial thrombotic event within the past 6 months. This includes angina (stable or unstable), MI, TIA, or CVA.
• Other Anticancer or Experimental Therapy.
• Women who are pregnant or breast-feeding.
• Patients with any other concurrent medical or psychiatric condition or disease which would make them inappropriate candidates for entry into this study.
• Patients with a history of anti-PD-1, anti-PD-L1, anti-PD-L2 or CEGFR TKI therapy.
• Patients underwent major surgery or had not recovered from the side effects of this surgery, received a vaccine, received immunotherapy within 4 weeks before the first use of the study drug, and received radiotherapy within 2 weeks.
• Patients who received hematopoietic stimulating factors therapy, such as G-CSF and erythropoietin, within 1 week before the first administration of the study drug.
• Patients are allergic to study medication and its ingredients.
• Patients have active lung disease (such as interstitial pneumonia, pneumonia, obstructive pulmonary disease, asthma) or active tuberculosis.
• Patients have any uncontrollable clinical problems, including but not limited to:
• Persistent or severe infection.
• Hypertension that can't be effectively controlled by drugs（ blood pressure reading of 150 over 90）.

Sponsors & Collaborators

• Peking University Cancer Hospital & Institute: lead

Study Sites (1)

Beijing Cancer Hospital

Beijing, 100142, China

RECRUITING

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

camrelizumab; Oxaliplatin; Capecitabine; Radiotherapy, Intensity-Modulated

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics

Central Study Contacts

Yingjie LI

CONTACT

+86 135 2018 6618; liyingjie@sina.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief, Unit III & Ostomy Service, Gastrointestinal Cancer center

Study Record Dates

• First Submitted: April 6, 2020
• First Posted: April 9, 2020
• Study Start: May 25, 2020
• Primary Completion: July 1, 2020
• Study Completion: April 1, 2022
• Last Updated: July 9, 2020

Record last verified: 2020-07

Locations

CN (1)