Multi-Line Therapy Trial in Unresectable Metastatic Colorectal Cancer.

• Conditions: nresectable Wild-Type KRAS Metastatic Colorectal Cancer; MedDRA version: 16.0Level: LLTClassification code 10052362Term: Metastatic colorectal cancerSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2013-001928-19-FR
• Lead Sponsor: GERCOR

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-05-22
• Last Update Posted: 27 January 2014

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 474

Inclusion Criteria

1. Signed and dated informed consent, and willing and able to comply with protocol requirements,
2. Histologically proven adenocarcinoma of the colon and/or rectum,
3. Wild-type KRAS tumor (local assessment, performed either on primary tumor or metastasis),
4. Metastatic disease confirmed,
5. No prior therapy for metastatic disease (in case of previous adjuvant therapy, interval from end of chemotherapy and relapse must be >6 months for fluoropyrimidine alone or >12 months for oxaliplatin-based, bevacizumab-based, or cetuximab-based therapy),
6. Duly documented unresectable metastatic disease, ie not suitable for complete carcinological surgical resection at inclusion [NB: patients with unresectable disease at study entry but with any potential of salvage surgery after induction therapy are eligible],
7. At least one measurable or evaluable lesion as assessed by CT-scan or MRI (Magnetic Resonance Imaging) according to RECIST v1.1,
8. Age =18 years,
9. ECOG Performance status (PS) 0-2,
10. Hematological status: neutrophils (ANC) =1.5x109/L; platelets =100x109/L; haemoglobin =9g/dL,
11. Adequate renal function: serum creatinine level <150µM,
12. Adequate liver function: serum bilirubin =1.5 x upper normal limit (ULN), alkaline phosphatase <5xULN,
13. Proteinuria <2+ (dipstick urinalysis) or =1g/24hour,
14. Baseline evaluations performed before randomization when the KRAS WT status is known: clinical and blood evaluations no more than 2 weeks (14 days) prior to randomization, tumor assessment (CT-scan or MRI, evaluation of non-measurable lesions) no more than 3 weeks (21 days) prior to randomization,
15. Female patients must commit to using reliable and appropriate methods of contraception during the trial and until at least six months after the end of study treatment (when applicable). Male patients with a partner of childbearing potential must agree to use contraception in addition to having their partner use another contraceptive method during the trial and until at least 6 months after the end of the study treatment,
16. Registration in a national health care system (CMU included for France).

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 237
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 237

Exclusion Criteria

1. History or evidence upon physical examination of CNS metastasis (e.g. non irradiated CNS metastasis, seizure not controlled with standard medical therapy), unless adequately treated,
2. Exclusive bone metastasis,
3. Uncontrolled hypercalcemia,
4. Pre-existing permanent neuropathy (NCI grade =2),
5. Uncontrolled hypertension (defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure >100 mmHg), or history of hypertensive crisis, or hypertensive encephalopathy,
6. Concomitant unplanned antitumor therapy (e.g. chemotherapy, molecular targeted therapy, immunotherapy),
7. Treatment with any investigational medicinal product within 28 days prior to study entry,
8. Other serious and uncontrolled non-malignant disease,
9. Gilbert’s syndrome,
10. Other concomitant or previous malignancy, except: i/ adequately treated in-situ carcinoma of the uterine cervix, ii/ basal or squamous cell carcinoma of the skin, iii/ cancer in complete remission for >5 years,
11. Major surgery (open biopsy, surgical resection, wound revision or any other major surgery involving entry into body cavity) or significant traumatic injury within the last 28 days prior to randomization, and/or minor surgical procedure including placement of a vascular device within 2 days of first study treatment,
12. Pregnant or breastfeeding women,
13. Patients with known allergy/hypersensitivity to any component of study drugs,
14. History of arterial thrombo and/or embolic event (e.g. myocardial infarction, stroke,…) within 6 months prior to randomization,
15. Total bowel obstruction,
16.History of abdominal fistula, GI perforation, intra-abdominal abscess or active GI bleeding within 6 months prior to randomization,
17. Serious, non-healing wound, active ulcer or untreated bone fracture,
18. History or evidence of inherited bleeding diathesis or significant coagulopathy at risk of bleeding,
19. Current or recent (within 10 days of randomization) use of aspirin (>325 mg/d), clopidogrel (>75 mg/d) or use of oral anticoagulants or thrombolytic agents.

Study & Design

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