Study of Chemotherapy Combination With Autologous Cell Immunotherapy in the Recurrent and Metastatic Colorectal Cancer

Phase III Clinical Study of PD-1 Monoclonal Antibody-activated Autologous Peripheral Blood T-lymphocyte (PD1-T) Combined With XELOX and Bevacizumab in the First-line Treatment of Recurrent and Metastatic Colorectal Cancer

This study evaluates the effect and safty of PD-1 monoclonal antibody-activated autologous peripheral blood lymphocyte (PD1-T) combined with XELOX and bevacizumab in the first-line treatment of recurrent and metastatic colorectal cancer. Half of participants receive PD1-T combined with XELOX and bevacizumab, while the other half will receive XELOX and bevacizumab.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: Bevacizumab Injection [Avastin]; Drug: Oxaliplatin; Drug: Capecitabine; Biological: PD1-T cells

• Study Type: Interventional
• Enrollment (Estimated): 198
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Xiubao Ren, MD. PhD.; Phone Number: 3173 86-22-23340123; Email: liangcoh@163.com
• Study Contact Backup: Name: Liang Liu, MD.; Phone Number: 3172 86-22-23340123; Email: renxiubao@tjmuch.com

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 300060
      • Recruiting
      • Tianjin Medical University Cancer Institute and Hospital
      • Contact: Liang Liu, MD.; Phone Number: 3172 86-22-23340123; Email: liangcoh@163.com
      • Contact: Xiubao Ren, MD. PhD.; Phone Number: 3173 86-22-23340123; Email: renxiubao@tjmuch.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Subjects who must meet all the following criteria should be selected:

1. Agreeing to participate in this study and signing a written informed consent.
2. Male or female,from 18 to 75 years (including 18 and 75 years).
3. The life expectancy is longer than 3 months and can be followed up.
4. Patients with metastatic colorectal cancer whose condition has progressed after operation or could not receive radical surgery at initial treatment, will be confirmed by histological /cytological and imaging examinations. According to RECIST 1.1 standard, there will be at least one measurable lesion.
5. Bevacizumab, oxaliplatin and capecitabine were not used at least 6 months before the first administration of the drug in the patients with metastatic colorectal cancer whose condition has progressed after operation.
6. ECOG score will be 0 or 1 within 7 days before randomization.

7. Within 14 days before the start of treatment, the results of laboratory test of blood routine, liver, kidney function and hormone levels must be met the following criteria:

   White blood cells: more than 3.0 × 109/L; Platelets: more than 100 × 109/L; Neutrophils: more than 1.5 × 109/L; Hemoglobin: more than 80g/L; Serum glutamate pyruvate transaminase: less than 2.5 folds of the upper normal limit (ULN); Serum glutamic-oxal (o) acetic transaminase: less than 2.5 × ULN; Serum bilirubin: less than 1.25 × ULN; Serum creatinine: less than 1.25 × ULN. Cortisol and thyroid function will be in the normal range.

8. The toxicity and side effects of previous chemotherapy will must be alleviated to grade 1 or below (except hair loss).If the subjects received major surgical treatment or radiotherapy of > 30 Gy, they must recover from the toxicity or complications of these interventions, that is, they can be enrolled after 6 months.
9. Female subjects must take effective contraceptive measures throughout the study period; serum or urine pregnancy test results must be negative during screening and the whole study period.
10. Male subjects should take effective contraceptive measures from the beginning of treatment to within 6 months after the end of treatment.

Exclusion Criteria:

Subjects who meet any of the following criteria could not participate in this study:

1. Bevacizumab or oxaliplatin or capecitabine were used within 6 months before the first use of the study drug.
2. Patients received major surgery or local radiotherapy of more than 30 Gy within six months before the first use of the drug; received local radiofrequency, ablation, cryotherapy or radiotherapy of 30 Gy or less within one month before the first use of the drug; or received anti-tumor monoclonal antibody (mAb), chemotherapy and targeted small molecule therapy within one month before the first use of the drug. Patients with metastases who can undergo radical surgery.
3. Other malignant tumors needed treatment within five years.
4. Allogeneic tissue/organ transplantation.
5. Participating in research drug therapy within 4 weeks before the first administration of the trial.
6. Systemic glucocorticoid therapy or any other form of immunosuppressive therapy (except glucocorticoid preconditioned with docetaxel) is being administered within 3 days before the first administration of the experimental therapy.
7. Previous treatment with PD-1/PD-L1 antibodies.
8. Over the past two years, patients with active autoimmune diseases requiring systemic treatment, such as the use of corticosteroids, or immunosuppressants. Substitution therapy (such as thyroxine, insulin, or physiological corticosteroid replacement therapy for adrenal or pituitary dysfunction) is not a systemic treatment.
9. Having bleeding tendency, high risk of bleeding or coagulation dysfunction, having a history of thrombosis within 6 months and/or hemoptysis within 3 months; being treated with full oral and/or parenteral anticoagulants and thrombolysis agents (preventive use of anticoagulants is permitted); having used aspirin or other non-steroidal anti-inflammatory drugs that inhibit platelet function within 10 days; / MR imaging showed that the tumors surrounded or invaded the large vessel lumen.
10. Patients with congenital or acquired immunodeficiency (e.g. HIV-infected persons), active hepatitis B (HBV-DNA > 10^3 copies/ml) or hepatitis C (hepatitis C antibody positive), and HCV-RNA higher than the detection limit of the analytical method.
11. Poorly controlled hypertension (systolic pressure 150 mmHg and/or diastolic pressure 100 mmHg), previous hypertension crisis and hypertensive encephalopathy, and severe cerebrovascular diseases.
12. Non-healing wounds, active peptic ulcer, tracheoesophageal fistula, gastrointestinal perforation and abdominal abscess within 6 months.
13. Subjects with active central nervous system (CNS) metastases and/or cancerous meningitis.
14. Patients with active infections requiring systemic intravenous therapy.
15. Mental illness or other illnesses, such as uncontrollable heart disease or pulmonary disease, diabetes, etc.
16. Subjects who are known to be allergic to any of the constituents of the drug being studied.
17. Subjects with a recent history of drug abuse (including alcohol) within one year.
18. Compliance is poor and can not cooperate with clinical research.
19. Female subjects who are pregnant or breastfeeding, or who are expected to be pregnant during the trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; Bevacizumab & Oxaliplatin & Capecitabine & PD1-T cells Bevacizumab, 7.5mg/kg, intravenous infusion, d1; Oxaliplatin, 130mg/m2, intravenous infusion, d1; Capecitabine, 1g/m2, oral administration, d1-14; PD1-T cells, 1x10^10 (10 billion), intravenous infusion, d17; Q3W, 6 cycles. After 6 cycles, Bevacizumab, 7.5mg/kg, intravenous infusion, d1; Capecitabine, 1g/m2, oral administration, d1-14; Q3W, maintenance treatment.	Drug: Bevacizumab Injection [Avastin]; Bevacizumab injection; Other Names: Avastin; Drug: Oxaliplatin; Oxaliplatin injection; Drug: Capecitabine; Capecitabine oral agent; Biological: PD1-T cells; PD1-T cells injection; Other Names: PD-1 monoclonal antibody-activated peripheral blood T-lymphocyte
Active Comparator: Arm 2: Control; Bevacizumab & Oxaliplatin & Capecitabine Bevacizumab, 7.5mg/kg, intravenous infusion, d1; Oxaliplatin, 130mg/m2, intravenous infusion, d1; Capecitabine, 1g/m2, oral administration, d1-14; Q3W, 6 cycles. After 6 cycles, Bevacizumab, 7.5mg/kg, intravenous infusion, d1; Capecitabine, 1g/m2, oral administration, d1-14; Q3W, maintenance treatment.	Drug: Bevacizumab Injection [Avastin]; Bevacizumab injection; Other Names: Avastin; Drug: Oxaliplatin; Oxaliplatin injection; Drug: Capecitabine; Capecitabine oral agent

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	PFS will be calculated from initiation of treat- ment until first progression, and patients alive in stable state will be censored at the time of last contact.	3 years

Collaborators and Investigators

• Sponsor: Tianjin Medical University Cancer Institute and Hospital
• Investigators: Study Chair: Xiubao Ren, MD. PhD., Tianjin Medical University Cancer Institute and Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2019
• Primary Completion (Estimated): August 1, 2023
• Study Completion (Estimated): August 1, 2023

Study Registration Dates

• First Submitted: April 28, 2019
• First Submitted That Met QC Criteria: May 12, 2019
• First Posted (Actual): May 15, 2019

Study Record Updates

• Last Update Posted (Actual): August 1, 2023
• Last Update Submitted That Met QC Criteria: July 28, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: safety; effcet
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Capecitabine; Oxaliplatin; Bevacizumab
• Other Study ID Numbers: B2019-023-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No