Title
Trial of Antigen Pulsed Dendritic Cells (APDC) in Metastatic Colorectal Cancer
Phase III Trial of Antigen Pulsed Dendritic Cells (APDC) Combined With Chemotherapy in Metastatic Colorectal Cancer
Phase
Phase 3Lead Sponsor
People's Liberation Army of ChinaStudy Type
InterventionalStatus
Unknown statusIndication/Condition
Metastatic Colorectal CancerIntervention/Treatment
fluorouracil leucovorin antigen pulsed dendritic cells oxaliplatin ...Study Participants
480This trial is to compare the efficacy and safety of modified FOLFOX6 [mFOLFOX6, a specific chemotherapy regimen of Oxaliplatin ,5-Fluorouracil and Leucovorin] chemotherapy plus Antigen Pulsed Dendritic Cells (APDC，a kind of autologous tumor lysates pulsed human dendritic cells vaccine) with modified chemotherapy alone in patients with metastatic colorectal cancer.
Metastatic colorectal cancer (CRC) patients will be randomly assigned (3:1) to receive either modified FOLFOX6 [mFOLFOX6] chemotherapy combined with Antigen Pulsed Dendritic Cells (Arm APDC + Chemotherapy), or chemotherapy alone (Arm Chemotherapy). Each patient recruited in the study will receive maximum 12 cycles of (14 days/cycle) mFOLFOX6 chemotherapy. Patients in Arm APDC + Chemotherapy will receive APDC vaccination in addition to chemotherapy in the cycle 1-3 and 7-9, and in cycle 4-6 and 10-12 receive only chemotherapy. APDC + Chemotherapy or Chemotherapy will be stopped in case of disease progression, intolerable toxicities, or patient withdrawal with the consent. After 12 cycles, patients in Arm APDC + Chemotherapy will receive 5-Fluorouracil treatment plus every 3 months APDC therapy and patients in Arm Chemotherapy will receive only 5-Fluorouracil treatment. PFS, ORR and OS will be assessed, and toxicity and immunologic effects will be monitored.
Patients in Arm APDC+Chemotherapy receive maximum 12 cycles (14days/cycle) mFOLFOX6 chemotherapy. Each cycle chemotherapy consist of Oxaliplatin at 85mg/ m2 infused for 2 hours only on day 1,and Leucovorin at 400 mg/m2 was administered intravenously for 2 hours, followed by continuous intravenous administration of 5-Fluorouracil at 400 mg/m2 (2.4g/m2 for 46 hours).On day 8 of cycle1-3 and 7-9, patients also receive APDC vaccine infusion in 100ml saline. After 12 cycles, patients in Arm APDC+chemotherapy will receive 5-Fluorouracil /Leucovorin (Leucovorin at 400 mg/m2/day administered intravenously for 2 hours, intravenous bolus of 5-Fluorouracil at 400 mg/m2 , followed by continuous intravenous administration of 5-Fluorouracil at 1200 mg/m2/d for 2 days, repeated every 2 weeks) plus APDC therapy (once every 3 months). Treatments will continue unless disease progression, intolerable toxicity or patients withdrawal).
Patients in Arm Chemotherapy receive maximum 12cycles (14days/cycle) mFOLFOX6 chemotherapy. Each cycle chemotherapy consist of Oxaliplatin at 85mg/ m2 infused for 2 hours only on day 1, and Leucovorin at 400 mg/m2 was administered intravenously for 2 hours, followed by continuous intravenous administration of 5-Fluorouracil at 400 mg/m2 (2.4g/m2 for 46 hours). After 12 cycles, patients in Arm chemotherapy will receive only 5-Fluorouracil /Leucovorin (Leucovorin at 400 mg/m2/day administered intravenously for 2 hours, intravenous bolus of 5-Fluorouracil at 400 mg/m2 , followed by continuous intravenous administration of 5-Fluorouracil at 1200 mg/m2/d for 2 days, repeated every 2 weeks). Treatments will continue unless disease progression, intolerable toxicity or patients withdrawal).
Patients in Arm APDC + Chemotherapy will receive APDC combined with chemotherapy.
Patients in Arm Chemotherapy will receive chemotherapy only.
Inclusion Criteria: Histologically confirmed adenocarcinoma of the colorectum with metastatic lesions and received no previous therapy for metastatic lesions; Be able to undergo surgical resection to obtain at least 1cm3 tumor tissues; The patients are from 18-75 years old regardless of gender; An estimated life expectancy of more than 6 months with ECOG≤2; Adequate hepatic, renal, and bone marrow functions: neutrophilic granulocyte≥1.5×109/L, Hb(hemoglobin)≥90g/L, PLT(platelets)≥100×109/L, serum Cr(creatinine)≤1.5-time upper normal limit, serum TBIL(total bilirubin)≤1.5-time upper normal limit, both serum ALT and AST(alanine aminotransferase and aspartate aminotransferase)≤2.5-time upper normal limit, hepatic metastases CRC patients' serum ALT/AST≤5-time upper normal limit; At least one measurable lesion after surgical resection (According to the standard of RECIST1.1 version: Response Evaluation Criteria in Solid Tumors 1.1 version); Written informed consent. Exclusion Criteria: Severe (ie, active) heart disease, such as coronary heart disease symptoms, the New York Heart Association (NYHA) II-class or more serious congestive heart failure or severe arrhythmia requiring medication intervention, or history of myocardial infarction within the last 12 months; severe pulmonary dysfunction; peripheral neuropathy; unstable hypertension; Metastases lesions> 50% of liver volume; Autoimmune diseases, organ transplantation requiring immunosuppressive therapy and patients requiring long-term systemic corticosteroid therapy; History of other malignant diseases (except cured basal cell carcinoma and cervical carcinoma in situ) in the last 5 years; Pregnant or lactating women (women at childbearing age in the baseline pregnancy test positive or pregnancy test not examined. Menopausal women have menopause at least 12 months); Acute or chronic infectious diseases in active phase; severe uncontrolled infection, or other serious uncontrolled concomitant diseases; Definite history of allergy or allergic constitutions; Chemotherapy, radiotherapy or immunotherapy within four weeks; Administration of other investigational drugs or procedures within four weeks.
