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

Metastatic Colorectal Cancer Clinical Trial

Official title:

Phase II Randomized Controlled Trial of FOLFOXIRI Compared to FOLFOX in First Line Treatment of Chemo-naive Metastatic Colorectal Cancer

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02128425
• Other study ID #: GIHSYSU06
• Status: Recruiting
• Phase: Phase 2
• First received: April 15, 2014
• Last updated: May 6, 2014
• Start date: April 2014
• Est. completion date: April 2018

Study information

• Verified date: April 2014
• Source: Sun Yat-sen University
• Contact: Yanhong Deng, M.D.
• Phone: 008613925106525
• Email: 13925106525[@]163.com
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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

Description:

Survival of patients with metastatic colorectal cancer is correlated with the proportion of patients who receive all the three active drugs , but not with the proportion of patients who receive any second-line therapy. A superior efficacy in PFS,ORR and OS of FOLFOXIRI has been reported with acceptable toxicity. Moreover,evidence suggests that continuous dosing metronomic chemotherapy may be more efficacious than interval-chemotherapy.

Therefore, a way to improve the outcome of metastatic colorectal cancer patients could be to administer a maintenance first-line regimen containing the three active agents.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 162
• Est. completion date: April 2018
• Est. primary completion date: February 2017
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• 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.

• Calculated creatinine clearance or 24 hour creatinine clearance = 50 mL/ min.

Exclusion Criteria:

• 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.

• Current or recent (within 4 weeks prior to starting study treatment) treatment of another investigational drug or participation in another investigational study.

• Continuous use of immunosuppressive agents (except the use of corticosteroids as anti-emetic prophylaxis/treatment).

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Colorectal Neoplasms
• Metastatic Colorectal Cancer

Intervention

Drug:
• FOLFOXIRI
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
• FOLFOX
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

Locations

Country	Name	City	State
China	Gastrointestinal Hospital, Sun Yat-sen University	Guangzhou	Guangdong

Sponsors (1)

Lead Sponsor	Collaborator
Sun Yat-sen University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Progression-free survival after re-introduction of chemotherapy (PFS2)		up to 24 months	No
Secondary	Response rate during re-introduction of chemotherapy	(CR + PR rate according to RECIST)	up to 12 months	No
Secondary	Early tumor shrinkage rate in 8 weeks after induction treatment		8 weeks	No
Secondary	Overall survival		up to 5 years	No
Secondary	toxicity and safety	Number of participants with adverse events as a measure of safety and tolerability according to NCI CTC 4.0	up to 24 months	Yes
Secondary	QLQ (QLQ C30) - scores according to EORTC QLQ-C30 scoring manual (Quality of life)		up to 36 months	No
Secondary	Translational research		up to 5 years	No