Clinical trial NCT02503150: Trial of Antigen Pulsed Dendritic Cells (APDC) in Metastatic Colorectal Cancer
Official title: Phase III Trial of Antigen Pulsed Dendritic Cells (APDC) Combined With Chemotherapy in Metastatic Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Metastatic Colorectal Cancer
Keywords: Colorectal Cancer
Tumor Therapeutic Vaccine
Dendritic Cell
Lead sponsor: Second Military Medical University
Sponsor class: OTHER
Collaborators: name: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
name: Changhai Hospital
name: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
name: Fudan University
name: Shanghai Changzheng Hospital
name: Zhejiang Cancer Hospital
name: Chinese PLA General Hospital
name: Peking University Cancer Hospital & Institute
name: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine
name: RenJi Hospital
name: Second Affiliated Hospital, School of Medicine, Zhejiang University
name: First People's Hospital of Hangzhou
name: 307 Hospital of PLA
name: Huashan Hospital
name: Ruijin Hospital
name: Shanghai Haixin Biotechnology Co. Ltd
First posted: 2015-07-20
Enrollment: 480
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Progression Free Survival, PFS
timeFrame: Up to approximately six years
Secondary outcomes:
measure: Objective Response
timeFrame: Up to approximately six years
measure: Overall Survival, OS
timeFrame: Up to approximately six years
measure: Clinical benefit Rate
timeFrame: Up to approximately six years
measure: Quality of Life
timeFrame: Up to approximately six months
measure: Adverse Events
timeFrame: Up to approximately six years
Other outcomes:
Locations:
Study officials:
affiliation: Second Military Medical University
name: Xuetao Cao, M.D.,Ph.D.
role: STUDY_CHAIR
affiliation: Second Military Medical University
name: Tao Wan, Ph.D.
role: STUDY_DIRECTOR
affiliation: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
name: Yuankai Shi, M.D.,Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: