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

NCT ID: NCT04340401

Last Updated: 2020-07-09

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-05-25
• Study Completion Date: 2022-04-30

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.

Detailed Description

The combined treatment model of neoadjuvant chemoradiotherapy treatment + radical rectal resection + adjuvant therapy has become the standard treatment model for locally advanced mid-low rectal cancer, However, the existing evidence shows that this comprehensive treatment method has reached the upper limit of efficacy and cannot continue to reduce the metastatic rate and improve the survival rate.

Recent studies have shown that PD-1 antibody inhibitors have excellent curative effects on the treatment of a variety of tumors and have good safety.

This study is a single-arm, single-center, prospective, phase II clinical study. It is designed to test the efficacy and safety of Total Neoadjuvant chmoradiation Treatment plus SHR1210 for High-risk locally advanced Rectal Cancer, Meanwhile, screening effective Biomarker base on neoantigen.

In this study, 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.

This study is designed to recruit 25 patients in all.

Conditions

Rectal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

TNT+SHR1210

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.

Group Type: EXPERIMENTAL

SHR-1210

Intervention Type: DRUG

Patients will receive 3 cycles induction CapeOX and SHR-1210

Oxaliplatin

Intervention Type: 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.

Capecitabine

Intervention Type: 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.

Intensity modulated radiotherapy

Intervention Type: RADIATION

patients will receive intensity modulated radiotherapy with capecitabine

Total mesorectal excision

Intervention Type: PROCEDURE

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

Interventions

SHR-1210

Patients will receive 3 cycles induction CapeOX and SHR-1210

Intervention Type: DRUG

Oxaliplatin

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.

Intervention Type: DRUG

Capecitabine

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.

Intervention Type: DRUG

Intensity modulated radiotherapy

patients will receive intensity modulated radiotherapy with capecitabine

Intervention Type: RADIATION

Total mesorectal excision

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

Intervention Type: PROCEDURE

Other Intervention Names

Camrelizumab; OXA; CAPE; IMRT; TME

Eligibility Criteria

Inclusion Criteria

• 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.
• FT3, FT4, TSH are Normal or abnormal without clinical significance.
• ECG examination is Normal or abnormal without clinical significance; Echocardiography shows that LVEF>50%.
• Patients must read, agree to, and sign a statement of Informed Consent prior to participation in this study.
• Patients show good adherence, follow -up on time. It is recommended that all patients provide tumor tissue samples (preferably fresh tissue samples) for pathological genetic testing prior to enrollment.
• Fertile men or women with potential for pregnancy must use highly effective contraception throughout the trial. And continue contraception for 12 months after treatment ends.

Exclusion Criteria

• 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:

1. Persistent or severe infection.

2. Hypertension that can't be effectively controlled by drugs（ blood pressure reading of 150 over 90）.

3. Uncontrolled diabetes

4. Heart disease (Class III / IV congestive heart failure or cardiac block as defined by the New York Heart Association)

5. Patient has or is suspected of having an autoimmune disease,Such as pituitary inflammation, colitis, hepatitis, nephritis, hyperthyroidism, hypothyroidism, etc.

• Patients have other serious, acute or chronic diseases or have abnormal test results, and the investigator judges that this may increase the patient's risk of participating in the trial or interfere with the results.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Peking University Cancer Hospital & Institute

OTHER

Sponsor Role: lead

Responsible Party

Aiwen Wu

Chief, Unit III & Ostomy Service, Gastrointestinal Cancer center

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Beijing Cancer Hospital

Beijing, , China

Site Status: RECRUITING

Countries

China

Central Contacts

Yingjie LI

Role: CONTACT

liyingjie@sina.com

+86 135 2018 6618

Facility Contacts

Yingjie Li, M.D.

Role: primary

liyingjiedr@sina.com

+86 135 2018 6618

Other Identifiers

PKUCH-R04

Identifier Type: -

Identifier Source: org_study_id