Trial of Antigen Pulsed Dendritic Cells (APDC) in Metastatic Colorectal Cancer

NCT ID: NCT02503150

Last Updated: 2015-07-30

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE3
• Total Enrollment: 480 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-07-31
• Study Completion Date: 2020-12-31

Brief Summary

This 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.

Detailed Description

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.

Conditions

Metastatic Colorectal Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

APDC + Chemotherapy

Patients in Arm APDC + Chemotherapy will receive APDC combined with chemotherapy.

Group Type: EXPERIMENTAL

APDC + Chemotherapy

Intervention Type: BIOLOGICAL

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).

Chemotherapy

Patients in Arm Chemotherapy will receive chemotherapy only.

Group Type: ACTIVE_COMPARATOR

Chemotherapy

Intervention Type: DRUG

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).

Interventions

APDC + Chemotherapy

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).

Intervention Type: BIOLOGICAL

Chemotherapy

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).

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Histologically confirmed adenocarcinoma of the colorectum with metastatic lesions and received no previous therapy for metastatic lesions;

2. Be able to undergo surgical resection to obtain at least 1cm3 tumor tissues;

3. The patients are from 18-75 years old regardless of gender;

4. An estimated life expectancy of more than 6 months with ECOG≤2;

5. 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;

6. 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);

7. Written informed consent.

Exclusion Criteria

1. 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;

2. Metastases lesions> 50% of liver volume;

3. Autoimmune diseases, organ transplantation requiring immunosuppressive therapy and patients requiring long-term systemic corticosteroid therapy;

4. History of other malignant diseases (except cured basal cell carcinoma and cervical carcinoma in situ) in the last 5 years;

5. 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);

6. Acute or chronic infectious diseases in active phase; severe uncontrolled infection, or other serious uncontrolled concomitant diseases;

7. Definite history of allergy or allergic constitutions;

8. Chemotherapy, radiotherapy or immunotherapy within four weeks;

9. Administration of other investigational drugs or procedures within four weeks.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

OTHER

Sponsor Role: collaborator

Changhai Hospital

OTHER

Sponsor Role: collaborator

Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

OTHER

Sponsor Role: collaborator

Fudan University

OTHER

Sponsor Role: collaborator

Shanghai Changzheng Hospital

OTHER

Sponsor Role: collaborator

Zhejiang Cancer Hospital

OTHER

Sponsor Role: collaborator

Chinese PLA General Hospital

OTHER

Sponsor Role: collaborator

Peking University Cancer Hospital & Institute

OTHER

Sponsor Role: collaborator

Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

OTHER

Sponsor Role: collaborator

RenJi Hospital

OTHER

Sponsor Role: collaborator

Second Affiliated Hospital, School of Medicine, Zhejiang University

OTHER

Sponsor Role: collaborator

First People's Hospital of Hangzhou

OTHER

Sponsor Role: collaborator

307 Hospital of PLA

OTHER

Sponsor Role: collaborator

Huashan Hospital

OTHER

Sponsor Role: collaborator

Ruijin Hospital

OTHER

Sponsor Role: collaborator

Shanghai Haixin Biotechnology Co. Ltd

UNKNOWN

Sponsor Role: collaborator

Second Military Medical University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Xuetao Cao, M.D.,Ph.D.

Role: STUDY_CHAIR

Second Military Medical University

Tao Wan, Ph.D.

Role: STUDY_DIRECTOR

Second Military Medical University

Yuankai Shi, M.D.,Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Central Contacts

Lan Bai, Mastor

Role: CONTACT

bailan@hisunbio.com

+86 18621696315

Ke Wang, Bachelor

Role: CONTACT

wangke@immunol.org

+86 13761172785

Other Identifiers

SMMU, Shanghai

Identifier Type: -

Identifier Source: org_study_id