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

Phase 3

• Conditions: Metastatic Colorectal Cancer
• Interventions: Drug: Chemotherapy; Biological: APDC + Chemotherapy

• Registration Number: NCT02503150
• Lead Sponsor: Second Military Medical University

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.

Study Timeline

• Status Verified: 2015-07
• Study Start: 2015-07
• Study First Submitted: 2015-07-16
• Study First Submitted QC: 2015-07-17
• Study First Posted: 2015-07-20
• Last Update Submitted: 2015-07-29
• Last Update Posted: 2015-07-30
• Primary Completion: 2019-12
• Study Completion: 2020-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 480

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Chemotherapy	Chemotherapy	Patients in Arm Chemotherapy will receive chemotherapy only.
APDC + Chemotherapy	APDC + Chemotherapy	Patients in Arm APDC + Chemotherapy will receive APDC combined with chemotherapy.

Primary Outcome Measures

Name	Time	Method
Progression Free Survival, PFS	Up to approximately six years	Time from the randomization date to the start of disease progression (progression assessed by investigator using Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1 guidelines) for metastatic colorectal cancer subjects.

Secondary Outcome Measures

Name	Time	Method
Overall Survival, OS	Up to approximately six years	From randomisation to the time of death of any cause.
Clinical benefit Rate	Up to approximately six years	From randomisation to confirmation of objective response
Adverse Events	Up to approximately six years	From randomisation to the end of follow-up
Quality of Life	Up to approximately six months	From randomisation to the end of all treatments (according to the EORTC QLQ-C30: European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire-C30)
Objective Response	Up to approximately six years	From randomisation to occurrence of objective response( complete regression (CR) and partial regression (PR) need to be confirmed 28 days after the occurrence)