FOLFOXIRI Compared to FOLFOX in First Line Treatment of Metastatic Colorectal Cancer

NCT02128425 | Unknown Phase 2

• 1 other identifier: GIHSYSU06
• Study Type: interventional
• Target: 162
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to evaluate if the exposure to all the three active cytotoxic agents (FOLFOXIRI regimen) is superior in terms of progression-free survival to conventional chemotherapy with the FOLFOX regimen as first-line treatment of chemo-naive metastatic colorectal cancer patients. A second primary aim is to evaluate the response rate, safety and tolerability of the chemotherapy of FOLFOXIRI regimen in this patient population. Patients will be randomized to two therapy groups: Experimental arm A: Chemotherapy with FOLFOXIRI Standard arm B: Chemotherapy with FOLFOX

Conditions

Metastatic Colorectal Cancer

Keywords

Colorectal cancer; Metastatic colorectal cancer; FOLFOXIRI; FOLFOX; Oxaliplatin; irinotecan; Leucovorin; 5-FU

Outcome Measures

Primary Outcomes (1)

• Progression-free survival after induction and maintenance chemotherapy (PFS1)

  Progressions are evaluated every 8 weeks according to WHO criteria and reviewed by an independent panel at the end of follow up (36 months).

  up to 18 months

Secondary Outcomes (7)

• Progression-free survival after re-introduction of chemotherapy (PFS2)

  up to 24 months

• Response rate during re-introduction of chemotherapy

  up to 12 months

• Early tumor shrinkage rate in 8 weeks after induction treatment

  8 weeks

• Overall survival

  up to 5 years

• toxicity and safety

  up to 24 months

Study Arms (2)

FOLFOXIRI

EXPERIMENTAL

FOLFOXIRI

Drug: FOLFOXIRI

FOLFOX

ACTIVE COMPARATOR

FOLFOX

Drug: FOLFOX

Interventions

FOLFOXIRI DRUG

irinotecan\* 165 mg/m² + oxaliplatin 85 mg/m² + leucovorin 200 mg/m² + 5-FU 3200 mg/m² cont. inf. 46h all on day 1 of each 2 weeks cycle \*reduced in UGT1A1 7/7 patients

Also known as: Irinotecan, Oxaliplatin, Leucovorin, 5-Fluorouracil

FOLFOXIRI

FOLFOX DRUG

oxaliplatin 85 mg/m² + leucovorin 400 mg/m² +5-FU 400mg/m² bolus iv.+ 5-FU 2400 mg/m² cont. inf. 46h all on day 1 of each 2 weeks cycle

Also known as: Oxaliplatin, Leucovorin, 5-Fluorouracil

FOLFOX

Eligibility Criteria

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

You may qualify if:

• Signed informed consent obtained before any study specific procedures. -Subjects must be able to understand and willing to sign a written informed consent.
• Male or female subjects ≥ 18 years ≤ 75 years of age
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 2.(ECOG PS 0-2 for≥18 years ≤ 65 years of age ，ECOG PS 0-1 for \>65 years of age)
• Histological or cytological documentation of adenocarcinoma of the colon or rectum. All other histological types are excluded.
• There must be documentation by PET/CT scan, CT scan, MRI, or intraoperative palpation (at the time of resection of the primary colorectal tumor, if applicable) that the patient has evidence of metastases (Histologic confirmation of metastasis is not required.).
• At least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria measured within 4 weeks prior to registration.
• No previous chemotherapy or target therapy for metastatic disease (adjuvant chemotherapy for non-metastatic disease is allowed if terminated more than 6 months ago).
• In case of previous radiotherapy, at least one measurable lesion should be located outside the irradiated field.
• Adequate bone marrow, hepatic and renal function as assessed by the following laboratory requirements conducted within 7 days of starting study treatment:
• Leukocytes ≥ 3.0 x109/ L, absolute neutrophil count (ANC) ≥ 1.5 x109/ L, platelet count ≥ 100 x109/ L, hemoglobin (Hb) ≥9g/ dL.
• Total bilirubin ≤ 1.5 x the upper limit of normal (ULN).
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 5 x ULN.
• Alkaline phosphatase limit ≤ 5x ULN.
• Amylase and lipase ≤ 1.5 x the ULN.
• Serum creatinine ≤ 1.5 x the ULN.

You may not qualify if:

• Previous palliative chemotherapy for metastatic disease，previous adjuvant chemotherapy including irinotecan or oxaliplatin within 6 months before random assignment.
• Previous or concurrent cancer that is distinct in primary site or histology from colorectal cancer within 5 years prior to randomization.
• Life expectancy \> 12 weeks;
• Extended field radiotherapy within 4 weeks or limited field radiotherapy within 2 weeks prior to randomization. Subjects must have recovered from all therapy-related toxicities.
• Major surgical procedure, open biopsy, or significant traumatic injury within 4 weeks before start of study medication.
• Congestive heart failure ≤ New York Heart Association (NYHA) class 2.
• Significant cardiovascular disease including unstable angina or myocardial infarction within 6 months before initiating study treatment or a history of ventricular arrhythmia
• Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within the 6 months before start of study medication.
• Any evidence of active infection.
• History of interstitial pneumonitis or pulmonary fibrosis
• Pregnancy or lactation at the time of study entry.
• Known dihydropyrimidine dehydrogenase (DPD) deficiency
• Any illness or medical conditions that are unstable or could jeopardize the safety of the subjects and his/her compliance in the study.
• Active inflammatory bowel disease or other bowel disease causing chronic diarrhoea
• Subjects with known allergy to the study drugs or to any of its excipients.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Gastrointestinal Hospital, Sun Yat-sen University

Guangzhou, Guangdong, 510655, China

RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

FOLFOXIRI protocol; Irinotecan; Oxaliplatin; Leucovorin; Fluorouracil; Folfox protocol

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)

Camptothecin; Alkaloids; Heterocyclic Compounds; Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Yanhong Deng, M.D.

  Sixth Affiliated Hospital, Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yanhong Deng, M.D.

CONTACT

008613925106525; 13925106525@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D

Study Record Dates

• First Submitted: April 15, 2014
• First Posted: May 1, 2014
• Study Start: April 1, 2014
• Primary Completion: February 1, 2017
• Study Completion: April 1, 2018
• Last Updated: May 7, 2014

Record last verified: 2014-04

Locations

CN (1)