Phase III study of an optimized chemotherapy + Avastin strategy +/- Tarceva in metastatic colorectal cancer. - Dream

• Conditions: Metastatic Colorectal Cancer; MedDRA version: 9.1Level: LLTClassification code 10052362Term: Metastatic colorectal cancer

• Registration Number: EUCTR2007-002797-56-AT
• Lead Sponsor: Gercor

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2007-07-23
• Last Update Posted: 10 July 2015

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 650

Inclusion Criteria

-Signed informed consent prior to inclusion.
-Histologically proven adenocarcinoma of colon or rectum.
-Metastatic disease confirmed.
-Duly documented inoperable metastatic disease, i.e. non suitable for complete carcinological surgical resection.
-No previous chemotherapy and/or immunotherapy for metastatic disease.
-In case of previous adjuvant chemotherapy, progression-free interval from end of previous adjuvant chemotherapy > 6 months (2 years if oxaliplatin or CPT11 received as adjuvant therapy)
-Measurable lesion as assessed by CT scan or MRI (Magnetic Resonance Imaging) in at least one dimension (longest diameter to be recorded) as 20mm with conventional CT scan or as 10 mm with spiral CT scan or non measurable lesions (all other lesions, including small lesions [<20mm conventional CT scan or <10mm spiral CT scan]).
-Age 18 years - 80 years.
-WHO (ECOG) performance status 0-2 (Appendix 5).
-Hematological status:
Neutrophils >= 1,5 109/L
Platelets >= 100 109/L
Haemoglobin > 9 g/dL (may be transfused to maintain or exceed this level)
-International Normalized Ratio (INR) <= 1.5; aPTT <1.5 x UNL (EXEMPTION: patients on full anticoagulation due to VTE must have an in-range INR (usually between 2 and 3). Any anticoagulation therapy must be at stable dosing prior to treatment start.)
-Renal function:
Serum creatinine: < 150 µmol/l.
Calculated creatinine clearance >30ml/min (dosage modification for
Capecitabine if creatinine clearance is < 30-50 ml/min)
- Proteinuria at baseline: Urine dipstick of proteinuria <2+. Patients discovered to have >=2+ proteinuria on dipstick urinalysis at baseline, should undergo a 24-hour urine collection and must demonstrate <= 1 g of protein/24 hr.
-Hepatic function:
Total bilirubin < 1.5 x upper normal limit (UNL)
Alkaline phosphatase: < 3 x ULN (<5 x ULN if liver metastasis)
-Neurologic status: no peripheral sensory neuropathy (NCI grade 0).
-Regular follow up feasible. A registered patient must be treated and followed at the participating center.
-Baseline evaluations performed before randomization: clinical and blood evaluations no more than 2 weeks prior to planned first course; tumoral assessment (chest X ray, CT scan or MRI, evaluation of non measurable disease) no more than 21 days prior to planned first course.
-First course of treatment planned less than 7 days after inclusion.
-In pre-menopausal women and women <2 years after the onset of menopause, a negative serum pregnancy test within 7 days before starting study treatment; or a negative serum pregnancy test within 28 days before starting study treatment, confirmed by a negative urine pregnancy test within 7 days prior to starting study treatment.
Fertile women and men of childbearing potential (<2 years after last menstruation in women) must use effective means of contraception (oral contraceptives, intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly or surgically sterilisation).

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

Exclusion Criteria

-Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to study treatment start, not fully healed wounds, or anticipation of the need for major surgical procedure during the course of the study. CVAD for chemotherapy administration must be inserted at least 2 days prior to treatment start
-Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to treatment start.
-LDH not done
-Both history of severe arterial thromboembolic events (MI, stroke) and age >65 years
-Baseline diarrhea grade >1
-Total or partial bowel obstruction.
-Pregnant or breast-feeding women.
-Duly documented metastatic stage suitable for immediate surgery.
-Previous palliative chemotherapy and/or immunotherapy for metastatic stage.
-History or evidence upon physical examination of CNS disease unless adequately treated (e.g., non irradiated CNS metastasis, seizure not controlled with standard medical therapy or history of stroke).
-Exclusive bone metastasis.
-Uncontrolled hypercalcemia.
-Other concomitant or previous malignancy, except adequately treated in situ carcinoma of the uterine cervix or basal or squamous cell carcinoma of the skin or cancer in complete remission for < 5 years.
-Concomitant antitumoral treatment.
-Participation in another clinical trial with any investigational drug within 30 days prior to inclusion.
-Symptomatic ascitis or pleural effusion not evacuated prior to entry into the study.
-Peripheral neuropathy (NCI CTC >= grade 1).
-Other serious non malignant disease:
•Pre-existing lung disease (in particular COLD, pleural effusion, lymphangitis carcinomatosis and intersticial syndrome)
•Clinically significant (i.e. active) cardiovascular disease for example cerebrovascular accidents (= 6 months prior to inclusion), myocardial infarction (within 1 year prior to inclusion), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication
•Uncontrolled hypertension (defined as systolic blood pressure > 150 mm Hg and/or diastolic blood pressure > 100 mm Hg) or prior history of hypertensive crisis or hypertensive encephalopathy.
•Evidence of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or patient at high risk from treatment complications
-Chronic, daily treatment with aspirin (>325mg/day)
-Evidence of bleeding diathesis or significant coagulopathy
-Serious, non-healing wound, ulcer, or untreated bone fracture
-Patients with known allergy to any excipients of study drugs.
-Any significant ophthalmological abnormality, especially severe dry eye syndrome, keratoconjunctivitis sicca, Sjögren syndrome, severe exposure keratitis or any other disorder likely to increase the risk of corneal epithelial lesions. The use of contact lenses is not recommended during the study.

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: To show superiority in Progression Free Survival (PFS) from the date of randomization with Avastin plusTarceva compared to Avastin alone.<br>;Secondary Objective: Overall survival (OS), Progression-free survival from the date of registration,<br>Response rate,<br>Chemotherapy-free interval,<br>Salvage surgery rate,<br>Tolerance and quality of life,<br>Pharmacogenetic, Pharmacoeconomics,<br>And correlation between K-Ras status and efficacy<br><br>Safety: <br>Adverse Events and Laboratory tests, graded according to the NCI CTCAE v3.0.<br>;Primary end point(s): To show superiority in Progression Free Survival (PFS) from the date of randomization with Avastin plusTarceva compared to Avastin alone.<br>