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A trial comparing 2 chemotherapies with personalized treatment with new drugs in patients with colorectal cancer

Conditions
metastatic unresectable colorectal cancer (mCRC) .
MedDRA version: 17.0Level: LLTClassification code 10052362Term: Metastatic colorectal cancerSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]
Registration Number
EUCTR2014-000543-33-BE
Lead Sponsor
Antwerp University Hospital
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Authorised-recruitment may be ongoing or finished
Sex
All
Target Recruitment
Not specified
Inclusion Criteria

- Patients with histological confirmed diagnosis of metastatic CRC
- Confirmed Ras WT status by central laboratory in UZA
- At least one measurable lesion according to RECIST version 1.1
- Evaluation of tumor disease according to RECIST by investigator, 4 weeks or less prior inclusion.
- No major surgery within 4 weeks prior to inclusion
- Wound healing completed
- Age =18 years
- Life expectancy > 3 months
- ECOG = 2
- Neutrophils = 1.500/µl
- Platelets = 100.000µl
- Hemoglobin > 9 g/dl
- Creatinine clearance > 30 ml/min, serum creatinine < 1.25 x upper normal limit
- Serum bilirubin < 1.25x upper normal limit, AST / ALT < 2.5 x ULN
- In case of liver metastasis, serum bilirubin < 1.5 x upper normal limit, AST/ALT < 5 x ULN
- Signed written informed consent
- Fertile women (< 2 years after last menstruation) and men of childbearing potential must use effective means of contraception (oral contraceptives, intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly or surgically sterile)
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 175
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 175

Exclusion Criteria

- Current and/or previous treatment with any other investigational agent or other biological agent (e.g. cetuximab).
- Participation in another clinical trial within 30 days prior to entering this study
Other conditions
- Inadequately controlled hypertension (defined as systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg)
- Prior history of hypertensive crisis or hypertensive encephalopathy
- NYHA Class II or greater CHF
- History of myocardial infarction or unstable angina within 6 months prior to Day 1
- Known CNS disease, except for treated brain metastasis (treated brain metastases are defined as having no evidence of progression or hemorrhage after treatment and no ongoing requirement fo dexamethasone, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period. Anticonvulsants (stable dose) are allowed. Treatment for brain metastases may include whole brain radiotherapy (WBRT), radio surgery (RS; Gamma Knife; LINAC; or equivalent) or a combination as deemed appropriate by the treating physician. Patients with CNS metastases treated by neurosurgical resection or brain biopsy performed within 3 months of start of study therapy will be excluded).
- Significant vascular disease (e.g. aortic aneurysm requiring surgical intervention, pulmonary embolism or recent peripheral arterial thrombosis) within 6 months prior start of study treatment.
- History of haemoptysis (= ½ teaspoon of bright red blood per episode) within 1 month prior to start of study treatment
- Evidence of bleeding diathesis or significant coagulopathy (in absence of therapeutic anticoagulation)
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to start of study therapy, or anticipation of need for major surgical procedure during the course of the study
- Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior start of study therapy.
- History of interstitial lung disease (eg, pneumonitis or pulmonary fibrosis) or evidence of interstitial lung disease on baseline CT scan.
- History of abdominal fistula or gastrointestinal perforation within 6 months prior to start of study therapy.
- Serious, non healing wound, active ulcer, or untreated bone fracture
- History or evidence upon physical/neurological
- Known hypersensitivity to any of the study drugs
- Acute intra abdominal inflammatory process
- 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
- Patients with contraindication for oxaliplatin containing chemotherapy (e.g. patients with serious polyneuropathy > grade 1)
- Previous radiotherapy: Patients must have recovered from any radiotherapy toxicity prior to enrolment
- Life expectancy less than 3 months
- 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
NameTimeMethod
Main Objective: - To assess Pogression Free Survival (PFS) of treatment;Secondary Objective: - To assess OS<br>- To evaluate Response Rate (RR) (RECIST version 1.1)<br>- To evaluate Duration of Response (DOR)<br>- To evaluate Time to Progression (TTP)<br>- To evaluate Time to Response (TTR)<br>- To evaluate Resection Rate?<br>- To evaluate the Safety profile of both combinations<br>- To study the relationship between the levels of proangiogenic cytokines / biomarkers and<br>outcome, PFS, OS.<br>- Health economic evaluation -To evaluate Quality of Life;Primary end point(s): Progression-free survival (PFS) rate at 1 years after randomisation ;Timepoint(s) of evaluation of this end point: 1 years after randomisation
Secondary Outcome Measures
NameTimeMethod
Secondary end point(s): - To evaluate Response Rate (RR) (RECIST version 1.1)<br>- To evaluate Resection Rate?<br>- To evaluate the Safety profile of both combinations<br>- To asses Overall Survival;Timepoint(s) of evaluation of this end point: after end of chemotherapy (3 month) in both arms <br>
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