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

NCT03950154 | Unknown Phase 3 DMC

• 1 other identifier: B2019-023-01
• Study Type: interventional
• Target: 198
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Colorectal Cancer

Keywords

effcet; safety

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (2)

Arm 1

EXPERIMENTAL

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]; Drug: Oxaliplatin; Drug: Capecitabine; Biological: PD1-T cells

Arm 2: Control

ACTIVE COMPARATOR

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]; Drug: Oxaliplatin; Drug: Capecitabine

Interventions

Bevacizumab Injection [Avastin] DRUG

Bevacizumab injection

Also known as: Avastin

Arm 1; Arm 2: Control

Oxaliplatin DRUG

Oxaliplatin injection

Arm 1; Arm 2: Control

Capecitabine DRUG

Capecitabine oral agent

Arm 1; Arm 2: Control

PD1-T cells BIOLOGICAL

PD1-T cells injection

Also known as: PD-1 monoclonal antibody-activated peripheral blood T-lymphocyte

Arm 1

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects who must meet all the following criteria should be selected:
• Agreeing to participate in this study and signing a written informed consent.
• Male or female,from 18 to 75 years (including 18 and 75 years).
• The life expectancy is longer than 3 months and can be followed up.
• 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.
• 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.
• ECOG score will be 0 or 1 within 7 days before randomization.
• 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.
• 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.
• 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.
• Male subjects should take effective contraceptive measures from the beginning of treatment to within 6 months after the end of treatment.

You may not qualify if:

• Subjects who meet any of the following criteria could not participate in this study:
• Bevacizumab or oxaliplatin or capecitabine were used within 6 months before the first use of the study drug.
• 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.
• Other malignant tumors needed treatment within five years.
• Allogeneic tissue/organ transplantation.
• Participating in research drug therapy within 4 weeks before the first administration of the trial.
• 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.
• Previous treatment with PD-1/PD-L1 antibodies.
• 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.
• 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.
• 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.
• Poorly controlled hypertension (systolic pressure 150 mmHg and/or diastolic pressure 100 mmHg), previous hypertension crisis and hypertensive encephalopathy, and severe cerebrovascular diseases.
• Non-healing wounds, active peptic ulcer, tracheoesophageal fistula, gastrointestinal perforation and abdominal abscess within 6 months.
• Subjects with active central nervous system (CNS) metastases and/or cancerous meningitis.
• Patients with active infections requiring systemic intravenous therapy.

Sponsors & Collaborators

• Tianjin Medical University Cancer Institute and Hospital: lead

Study Sites (1)

Tianjin Medical University Cancer Institute and Hospital

Tianjin, Tianjin Municipality, 300060, China

RECRUITING

Related Publications (1)

• Pan QZ, Zhao JJ, Liu L, Zhang DS, Wang LP, Hu WW, Weng DS, Xu X, Li YZ, Tang Y, Zhang WH, Li JY, Zheng X, Wang QJ, Li YQ, Xiang T, Zhou L, Yang SN, Wu C, Huang RX, He J, Du WJ, Chen LJ, Wu YN, Xu B, Shen Q, Zhang Y, Jiang JT, Ren XB, Xia JC. XELOX (capecitabine plus oxaliplatin) plus bevacizumab (anti-VEGF-A antibody) with or without adoptive cell immunotherapy in the treatment of patients with previously untreated metastatic colorectal cancer: a multicenter, open-label, randomized, controlled, phase 3 trial. Signal Transduct Target Ther. 2024 Apr 3;9(1):79. doi: 10.1038/s41392-024-01788-2.

  PMID: 38565886 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Bevacizumab; Oxaliplatin; Capecitabine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Organic Chemicals; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Xiubao Ren, MD. PhD.

  Tianjin Medical University Cancer Institute and Hospital

  STUDY CHAIR

Central Study Contacts

Xiubao Ren, MD. PhD.

CONTACT

86-22-23340123; liangcoh@163.com

Liang Liu, MD.

CONTACT

86-22-23340123; renxiubao@tjmuch.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 28, 2019
• First Posted: May 15, 2019
• Study Start: June 1, 2019
• Primary Completion: August 1, 2023
• Study Completion: August 1, 2023
• Last Updated: August 1, 2023

Record last verified: 2023-07

Locations

CN (1)