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Phase II Study of Toripalimab Plus Stereotactic Body Radiotherapy in Colorectal Cancer Patients With Oligometastasis

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: NCT03927898
Recruitment Status : Recruiting
First Posted : April 25, 2019
Last Update Posted : April 25, 2019
Sponsor:
Collaborator:
Shanghai Junshi Bioscience Co., Ltd.
Information provided by (Responsible Party):
Jing Jin, M.D., Chinese Academy of Medical Sciences

Brief Summary:

Metastatic colorectal cancer is one of the common malignant tumors and the overall prognosis is poor. The introduction of immune-checkpoint inhibition (ICI) has led to a paradigm shift in the treatment of patients with metastatic cancer. Stereotactic body radiation therapy (SBRT) delivers a large dose of radiation to the tumor target with high precision while sparing irradiation of the surrounding normal tissues. It is suggested that SBRT could be the most appropriate radiotherapy modality to be combined with immunotherapy since it induces the expression of a series of cytokines and new tumour-associated antigens (TAAs) and is more likely to cause intense immune response and exert an abscopal effect than conventional radiotherapy.

Thus, this study is to explore the use of SBRT in combination with ICI in colorectal cancer patients with oligometastasis, in order to get better local and systemic tumor control and improve progress-free survival (PFS).


Condition or disease Intervention/treatment Phase
Metastatic Colorectal Cancer Drug: Toripalimab Radiation: Stereotactic Body Radiotherapy Phase 2

Detailed Description:
The investigators plan to recruit patients with mCRC, who have received first-line systemic therapy for more than 3 months and achieved PR/SD. Than all the patients will receive SBRT followed by ICI therapy.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: All enrolled patients will receive Toripalimab following stereotactic body radiotherapy
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of Toripalimab (JS001) Plus Stereotactic Body Radiotherapy in Colorectal Cancer Patients With Oligometastasis
Actual Study Start Date : March 1, 2019
Estimated Primary Completion Date : March 1, 2021
Estimated Study Completion Date : September 1, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: SBRT+Toripalimab
Participants received SBRT (BED>80Gy) to oligometastatic lesions and then receive Toripalimab (240mg)/q3w till progression of disease.
Drug: Toripalimab
Participants receive Toripalimab (240mg)/q3w till progression of disease after SBRT

Radiation: Stereotactic Body Radiotherapy
Participants receive SBRT (BED>80Gy) to oligometastatic lesions followed by Toripalimab (240mg)/q3w




Primary Outcome Measures :
  1. 1 year Progression-Free-Survival (PFS) [ Time Frame: 1 year ]
    1 year PFS


Secondary Outcome Measures :
  1. Grade 3-5 acute adverse events [ Time Frame: 6 months since last treatment of Toripalimab ]
    Grade 3-5 acute adverse events

  2. Objective response rate [ Time Frame: At the end of 4 cycles of Toripalimab (each cycle is 21 days) ]
    Objective response rate

  3. 2 year local control rate [ Time Frame: 2 year ]
    2 year local control rate

  4. 2 year overall survival [ Time Frame: 2 year ]
    2 year overall survival

  5. T cell receptor repertoire and T cell clones in peripheral blood [ Time Frame: At the end of 6 cycles of Toripalimab (each cycle is 21 days) ]
    Change of T cell receptor repertoire and T cell clones in peripheral blood

  6. Expression of PD-1, ki-67 on T cell [ Time Frame: At the end of 6 cycles of Toripalimab (each cycle is 21 days) ]
    Change of expression of PD-1, ki-67 on T cell

  7. Expression of PD-L1 on Exosomes in peripheral blood [ Time Frame: At the end of 6 cycles of Toripalimab (each cycle is 21 days) ]
    Change of expression of PD-L1 on Exosomes in peripheral blood

  8. Expression of PD-L1 on circulation tumor cell [ Time Frame: At the end of 6 cycles of Toripalimab (each cycle is 21 days) ]
    Change of expression of PD-L1 on circulation tumor cell



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.


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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age:18-75 years old , Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
  2. Histologically confirmed CRC , metastatic CRC , subjects have received first-line systemic therapy for more than 3 months and achieved PR/SD, the interval between last systemic therapy and SBRT is≥4 weeks
  3. The primary site has been controlled by surgery
  4. Patient has at least 1 lesion of measurable metastatic disease by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and iRECIST , and who can achieve the status of non evidence of disease after local ablative therapy. The number of lesion is ≤ 5, the maximum diameter of the lesion is ≤5cm ,
  5. All metastatic lesions are amenable to SBRT with BED≥80Gy in 3 to 5 fractions;
  6. Have a life expectancy of at least 6 months
  7. Adequate organ function, as defined by the following:

    Hemoglobin ≥ 100 g/L; White blood cell count (WBC) ≥3.5×109/L , Absolute neutrophil count (ANC) ≥ 1.5×109/L; Platelets ≥75×109/L; Serum creatinine ≤ 1.0 x institutional upper limit of normal (ULN) ; Blood Urea Nitrogen(BUN) ≤ 1.0 x institutional (ULN) Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 1.5 x institutional ULN ALkaline Phosphatase (ALP) ≤ 1.5 x institutional ULN Serum total bilirubin (TBIL) ≤1.5 x institutional ULN Urine protein is negative , Coagulation function is normal

  8. patients and his/her mate must agree to follow instructions for method(s) of contraception for the duration of treatment with study drug;
  9. Patient must have the ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

  1. Serious autoimmune disease at the discretion of the treating attending,subjects with leukodermia,allergic asthma syndrome will not be excluded from the study.
  2. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
  3. Has evidence of interstitial lung disease or active, non-infectious pneumonitis requiring systemic steroids.
  4. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to study Day 1 of the trial treatment.
  5. Has a known additional malignancy,subjects with basal cell carcinoma (BCC), squamous cell carcinoma of skin and carcinoma in situ of cervix will not be excluded from the study.
  6. Has received a vaccine within 30 days prior to study Day 1 of the trial treatment or will receive a vaccine after the trial treatment; active HBV,HCV infection
  7. Has received systemic therapy within 4 weeks prior to study Day 1 of the trial treatment or who has not recovered from adverse events due to a previously administered agent.

    Note: Subjects with ≤ Grade 2 neuropathy or myelosuppression are an exception to this criterion and may qualify for the study.

  8. Any underlying medical or psychiatric condition: partial endocrine organ deficiencies , serious cardiac,pulmonary,renal disease,active infectious disease.
  9. Active diverticulitis, intra-abdominal abscess, Gastrointestinal (GI) obstruction, abdominal carcinomatosis , frequent diarrhea or other known risk factors for bowel perforation.

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): NCT03927898


Contacts
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Contact: Jing Jin, M.D +86-1087787568 jingjin1025@163.com
Contact: Jianyang Wang, M.D. +86-1087788122 pkucell@163.com

Locations
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China, Beijing
Department of Radiation Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College Recruiting
Beijing, Beijing, China, 100021
Contact: Wenyang Liu, MD       liuwenyang26@163.com   
Department of Radiation Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College Recruiting
Beijing, Beijing, China, 100021
Contact: Jianyang Wang, MD    +86-13810095191    pkucell@163.com   
Contact: Jing Jin, MD    +86-10-87788122    jingjin1025@163.com   
China
Department of Radiation Oncology, Cancer Institute and Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College Recruiting
Beijing, China, 100021
Contact: Jing Jin, MD    +8613601365130    jingjin1025@163.com   
Sponsors and Collaborators
Chinese Academy of Medical Sciences
Shanghai Junshi Bioscience Co., Ltd.
Publications:

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Responsible Party: Jing Jin, M.D., Professor of Dept.of Radiation Oncology, Chinese Academy of Medical Sciences
ClinicalTrials.gov Identifier: NCT03927898    
Other Study ID Numbers: 18-223/1781
First Posted: April 25, 2019    Key Record Dates
Last Update Posted: April 25, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases