Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04340401
Recruitment Status : Recruiting
First Posted : April 9, 2020
Last Update Posted : July 9, 2020
Sponsor:
Information provided by (Responsible Party):
Aiwen Wu, Beijing Cancer Hospital

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.

Condition or disease Intervention/treatment Phase
Rectal Cancer Drug: SHR-1210 Drug: Oxaliplatin Drug: Capecitabine Radiation: Intensity modulated radiotherapy Procedure: Total mesorectal excision Phase 2

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 25 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Total Neoadjuvant Chmoradiation Treatment Plus SHR1210 for High-risk Locally Advanced Rectal Cancer and Biomarker Screening Base on Neoantigen
Actual Study Start Date : May 25, 2020
Estimated Primary Completion Date : July 2020
Estimated Study Completion Date : April 2022

Arm Intervention/treatment
Experimental: 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.

Drug: SHR-1210
Patients will receive 3 cycles induction CapeOX and SHR-1210
Other Name: Camrelizumab

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.
Other Name: OXA

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.
Other Name: CAPE

Radiation: Intensity modulated radiotherapy
patients will receive intensity modulated radiotherapy with capecitabine
Other Name: IMRT

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




Primary Outcome Measures :
  1. pathologic complete response rate(pCR rate) [ Time Frame: 1 month after surgery ]
    The number of patients with pCR divided by the total number of patients


Secondary Outcome Measures :
  1. Toxicity of TNT+SHR-1210 [ Time Frame: 90 days after neoadjuvant treatment ]
    Category and grade of adverse event during neoadjuvant chemotherapy

  2. Change of TCR repertoire [ Time Frame: 1 week before surgery ]
    Use neoantigen model to find biomarkers related to the effect of TNT+SHR1210 for patients with rectal cancer; compare and analyze the differences in TCR repertoire changes in peripheral blood.

  3. Disease-free survival (DFS) [ Time Frame: 3 years ]
    The 3-year DFS will be defined as the percentage of patients alive without local recurrence or distant metastasis of disease at 3 years measured from the date of the administration of treatment.

  4. Surgical complication rate [ Time Frame: 30 days after surgery ]
    Rate of patients who had surgical complications during the perioperative period

  5. Major adverse events [ Time Frame: 90 days after the last use of SHR-1210 ]
    Adverse events will be graded using the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04340401


Contacts
Layout table for location contacts
Contact: Yingjie LI +86 135 2018 6618 liyingjie@sina.com

Locations
Layout table for location information
China
Beijing Cancer Hospital Recruiting
Beijing, China, 100142
Contact: Yingjie Li, M.D.    +86 135 2018 6618    liyingjiedr@sina.com   
Principal Investigator: Aiwen Wu, M.D.         
Sponsors and Collaborators
Beijing Cancer Hospital
Layout table for additonal information
Responsible Party: Aiwen Wu, Chief, Unit III & Ostomy Service, Gastrointestinal Cancer center, Beijing Cancer Hospital
ClinicalTrials.gov Identifier: NCT04340401    
Other Study ID Numbers: PKUCH-R04
First Posted: April 9, 2020    Key Record Dates
Last Update Posted: July 9, 2020
Last Verified: July 2020

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Aiwen Wu, Beijing Cancer Hospital:
High-risk locally advanced Rectal cancer
SHR-1210
Total Neoadjuvant chmoradiation Treatment
pCR rate
Additional relevant MeSH terms:
Layout table for MeSH terms
Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Capecitabine
Oxaliplatin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents