Clinical trial to evaluate the efficacy of 5FU/LV, Oxaliplatin and Bevacizumab with or without Irinotecan in first-line treatment for metastatic colorectal cancer.

Phase 1

• Conditions: nresectable stage IV (UICC) colorectal cancer (primary tumor may be present); MedDRA version: 19.1Level: PTClassification code 10010035Term: Colorectal cancer stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2010-022162-27-DE
• Lead Sponsor: Martin-Luther-Universität Halle-Wittenberg

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-04-08
• Last Update Posted: 4 December 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 250

Inclusion Criteria

1) Patients with histologically confirmed diagnosis of unresectable stage IV (UICC) colorectal cancer (primary tumor may be present)
2) Patients with at least one measurable lesion, with size > 1 cm (RECIST v1.1)
3) ECOG Performance status = 2
4) Life expectancy > 3 months
5) Age = 18 years.
6) Haematologic function as follows: ANC = 1.5 x 109/L, platelets = 100 x109/L, hemoglobin = 9 g/dl or 5.59 mmol/l
7) INR <1.5 within 7 days prior to starting study treatment. aPTT < 1.5 x ULN within 7 days prior to starting study treatment.
8) Adequate liver function as measured by serum transaminases (AST & ALT) =< 2.5 x ULN (in case of liver metastases < 5 x ULN) and total bilirubin £ 1.5 x ULN
9) Adequate renal function: Serum creatinine =< 1.5 x ULN
10) Signed, written informed consent
11) At least 6 months after completion of adjuvant chemotherapy

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 250
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 25

Exclusion Criteria

1) Treatment with any other investigational agent, or participation in another clinical trial within 30 days prior to entering this study.
2) Prior systemic or local treatment of metastatic disease.
3) Prior adjuvant or neo-adjuvant chemotherapy/radiotherapy completed less than 6 months prior to study entry.
4) Pre History or evidence upon physical/neurological examination of CNS disease (unrelated to cancer) (unless adequately treated with standard medical therapy) e.g. uncontrolled seizures.
5) Fertile women (< 1 year after last menstruation) and men of childbearing potential unwilling or unable to use effective means of contraception.
6) Pregnancy or lactation.
7) Positive serum pregnancy test within 7 days of starting study treatment in pre-menopausal women and women < 1 year after the onset of menopause.
8) Other malignancies within the last 2 years prior to treatment start except metastatic colorectal cancer (patients with curatively treated basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix are eligible).
9) Peripheral neuropathy NCI CTCAE-grade = 1
10) Known DPD-insufficiency.
11) Active inflammatory bowel disease or other bowel disease causing chronic diarrhea (defined as > 4 loose stools per day)
12) History of interstitial lung disease, haemoptoe or evidence of interstitial lung disease on baseline chest X-ray or CT scan.
13) Serious, non-healing wound, ulcer or bone fracture.
14) Thrombosis or severe bleeding within 6 months prior to entry into the study (except for bleeding of the tumor before its surgical resection) and no evidence of bleeding diathesis or coagulopathy.
15) Urine dipstick for proteinuria = 2+. If urine dipstick is = 2+, 24-hour urine must demonstrate =< 1 g of protein in 24 hours for patient to be eligible.
16) Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to treatment.
17) Clinically significant cardiovascular disease, for example CVA, myocardial infarction, unstable angina, NYHA Class II CHF, arrhythmia requiring medication, or uncontrolled hypertension.
18) Evidence of any other disease, metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or puts the patient at high risk for treatment-related complications.
19) Known hypersensitivity or contraindication to the drugs used in the trial (eg: 5-FU, folinic acid/ leucovorin, capecitabine, oxaliplatin, bevacizumab, irinotecan)
20) Concomitant treatment with ASS > 325 mg or NSAIDs, known to inhibit platelet function, sorivudin or analog compounds or preparations of St. John’s wort
21) Inability or unwillingness to comply with the protocol

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of this study is to evaluate the efficacy of 5-Fluorouracil (5-FU), oxaliplatin and irinotecan (FOLFOXIRI-Regimen) with bevacizumab versus 5-FU and oxaliplatin (FOLFOX-Regimen) with bevacizumab in patients with metastatic colorectal cancer.;Secondary Objective: Secondary objectives are safety and tolerability of the treatment as well as the progression free survival, overall survival, secondary resection rate, quality of life and the prognostic value of and the allocation to the clinical classification of patients.;Primary end point(s): Efficacy of the four drug combination shown by Progression Free Survival Rate at 9 months. The Progression Free Survival Rate at 9 months will be determined by the proportion of patients being alive without progressive disease 9 months after randomization.;Timepoint(s) of evaluation of this end point: 2014