The Efficacy of JS001 Combined With Chemotherapy in Patients With Locally Advanced Colon Cancer

NCT03985891 | Recruiting Phase 1 DMC

• 1 other identifier: JSFOL--CC. V1.0
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Colon cancer is one of the most lethal malignancies, and colorectal cancer ranks the fifth leading cause of tumor-related mortality in China. FOLFOX is the recommended adjuvant/ neoadjuvant treatment for advanced colon cancer. JS001, as the first Chinese produced anti-PD-1 monoclonal antibody, has been approved by CFDA. This study aims to assess the safety and efficacy of JS001 in combination with FOLFOX as adjuvant/neoadjuvant treatment for patients with locally advanced colon cancer.

Conditions

Colonic Neoplasms; Chemotherapy Effect

Keywords

Colon cancer; PD-1; Chemotherapy

Outcome Measures

Primary Outcomes (3)

• pCR rate

  Pathologic complete response rate

  From the initiation date of first cycle to the date of operation, up to 5 months (each cycle is 2 weeks)

• rCR rate

  Radiographic complete response rate

  From the initiation date of first cycle to the date of operation, up to 5 months (each cycle is 2 weeks)

• ORR

  Immunotherapy overall response rate

  From the initiation date of first cycle to the date of operation, up to 5 months (each cycle is 2 weeks)

Secondary Outcomes (2)

• DFS

  From the initiation date of first cycle to the date of first documented progression, loss to follow up or death from any causes, whichever came first, up to 5 years (each cycle is 2 weeks)

• OS

  From the initiation date of first cycle to the date of death from any causes or loss to follow up, whichever came first, up to 5 years (each cycle is 2 weeks)

Study Arms (2)

JS001 in combination with Folfox

EXPERIMENTAL

Patients who meet the enrollment criteria will receive Folfox(Oxaliplatin 85mg/m2 iv Day1; Leucovorin 400mg/m2 iv Day1; 5-FU 400mg/m2 iv bolus on Day1, then1200mg/m2/d x 2days(total 2400mg/m2 over 46-48 hours) iv continuous infusion repeat every 2 weeks) in combination with JS001 (3mg/kg, Q2W). Patients will receive 6 cycles treatment in pre-operation and same cycles after operation.

Drug: Anti-PD-1 Monoclonal Antibody JS001; Drug: Chemotherapy

Folfox

ACTIVE COMPARATOR

Patients who meet the enrollment criteria will receive Folfox(Oxaliplatin 85mg/m2 iv Day1; Leucovorin 400mg/m2 iv Day1; 5-FU 400mg/m2 iv bolus on Day1, then1200mg/m2/d x 2days(total 2400mg/m2 over 46-48 hours) iv continuous infusion repeat every 2 weeks). Patients need to receive 6 cycles treatment in pre-operation and same cycles after operation.

Drug: Chemotherapy

Interventions

Anti-PD-1 Monoclonal Antibody JS001 DRUG

Anti-PD-1 monoclonal antibody combined with chemotherapy in patients with locally advanced colon cancer (perioperative treatment)

Also known as: Toripalimab

JS001 in combination with Folfox

Chemotherapy DRUG

Folfox

Also known as: Folfox

Folfox; JS001 in combination with Folfox

Eligibility Criteria

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

You may qualify if:

• Locally advanced colon cancer patients diagnosed by pathologic biopsy，and the patients have defined indications for neoadjuvant chemotherapy by MDT group.
• Patients may be available to undergo surgery.
• Patient has at least 1 measurable lesions according to RECIST version 1.1;
• Males and females aged ≥18 years.
• ECOG score 0-1; Estimate life ≥1 year.
• The main organs and bone marrow function are basically normal:
• (1) Blood test White blood cell count (WBC)≥2000/mm\^ 3; Absolute neutrophil count (ANC)≥1000/mm\^ 3; Blood platelet count ≥100000/mm\^ 3; Hemoglobin ≥9g/d; Serum creatine ≤ 2.0mg/dL; (2) Liver function Serum total bilirubin (TBIL) is within the normal range (normal range specified by the institution; Total bilirubin of Gilbert syndrome \<3.0mg/dL); Serum Aspartate Transaminase (AST), serum Alanine Aminotransferase Transaminase (ALT) and alkaline phosphatase (ALP) ≤ 2.5 \* upper limit of normal (ULN); International normalized ratio (INR) ≤1.5(or the patient is taking Warfarin for a long time, INR=2-3), and prothrombin time (PTT) ≤ULN (3) Pulmonary function Carbon Monoxide Diffusing Capacity (DLCO) ≥70% predictive OR; DLCO\<70% and ≥55% , and the maximal oxygen consumption VO2 max ≥10L/min/Kg (cardiopulmonary assessment) or 6 minute walk experiment ≥500 meters; Patients with DLCO \<55% are not included in this study; Pulse oximetry at rest or walking ≥92% (4) Cardiac function Baseline ECG showes no PR interval prolongation or atrioventricular block; 7. Patient and his/her mate must agree to follow instructions for method of contraception for the duration of the study period and within 6 months of the end of the study (eg. Intrauterine device, birth control pills or condoms); Serum or urine pregnancy test is negative within 7days prior to study enrollment and must be non-lactating; 8. Patients voluntarily joined the study, signed informed consent document, and were well compliant and able to be followed up with testers.

You may not qualify if:

• Any previous active autoimmune disease (including any history of inflammatory bowel disease), or history of diseases to be treated with systemic steroids or immunosuppressive drugs(except for vitiligo patients）；
• Use vaccines against infectious diseases (such as flu, chickenpox, etc.) within 4 weeks (28 days) of starting the study treatment;
• Active systemic infection requiring treatment, positive detection of hepatitis B surface antigen or hepatitis C ribonucleic acid (RNA);
• A known positive history or positive test result of human immunodeficiency virus or acquired immunodeficiency syndrome (AIDS);
• Patients with any severe and/or uncontrolled diseases, such as (1)unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months before randomization, severe uncontrolled arrhythmia；Patients with unsatisfactory blood pressure control (systolic blood pressure \>140mmHg,diastolic blood pressure\>90mmHg); (2) active or uncontrolled severe infection; (3) liver diseases such as cirrhosis, (4) decompensated liver disease, chronic active hepatitis; poor diabetes control (fasting blood glucose (FBG)\> 10mmol/L); (5) urinary routine indicates urinary protein\>or=++, and confirmed 24-hour urine protein quantitative \>1.0g; (6) having a history of psychotropic substance abuse and being unable to quit or have mental disorders;
• Pevious treatment with any anti-tumor treatment, including but not limited to chemotherapy, radiotherapy, immunotherapy (such as anti-PD-1, anti-PD-L1, anti-PD-L2 or anti-CTLA-4 antibodies or any other antibodies that target the T cell co-regulatory pathway), etc; Tumor-related therapies or online anticancer drugs are currently being used; Anticoagulant is currently in use; Received major surgery in the past 3weeks;
• Studies with previous malignancies, unless complete remission is achieved at least 2 years prior to the start of the study and no other treatment (subjects with basal cell carcinoma of skin and carcinoma in situ of cervix will not be excluded from the study);
• History of previous interstitial lung disease, drug-induced interstitial lung disease, radiation pneumonitis, symptomatic interstitial lung disease, or evidence of any activepneumonia found on chest CT scans within 4 weeks prior to the first study drug treatment.
• Immunosuppressive drugs were used within 2weeks prior to the first study drug treatment, excluding topical glucocorticoids, systemic glucocorticoids ≤ 10mg/day of prednisone or equivalent doses of other glucocorticoids;
• Pregnant or lactating female;
• Prisoners who are illegally imprisoned or compulsory for non-mental illness or physical (eg infectious disease) illness;
• Patients with bleeding tendency (such as active gastrointestinal ulcers) or treatment with anticoagulants or vitamin K antagonists such as warfarin, heparin or the like;
• A history of allergic reactions to the interventions;
• According to the investigator's judgment, there are serious concomitant diseases that endanger the safety of the patient or affect the patient's completion of the study;
• \. Has received a vaccine within 30 days prior to the study.

Sponsors & Collaborators

• Xiangya Hospital of Central South University: lead

Study Sites (1)

Shan Zeng

Changsha, Hunan, 410008, China

RECRUITING

MeSH Terms

Conditions

Colonic Neoplasms

Interventions

toripalimab; Drug Therapy; Folfox protocol

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Shan Zeng, Ph.D, MD.

  Xiangya Hospital of Central South University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shan Zeng, Ph.D, MD.

CONTACT

(86)-731-84327633; zengshan2000@csu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director，Chief Physician & Professor

Study Record Dates

• First Submitted: June 6, 2019
• First Posted: June 14, 2019
• Study Start: December 16, 2020
• Primary Completion: June 1, 2025
• Study Completion: June 1, 2026
• Last Updated: December 17, 2020

Record last verified: 2020-12

Locations

CN (1)