- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01640405
Study of 5-Fluorouracil/Leucovorin/Oxaliplatin (FOLFOX) + Bevacizumab Versus 5-Fluorouracil/Leucovorin/Oxaliplatin/Irinotecan (FOLFOXIRI) + Bevacizumab as First Line Treatment of Patients With Metastatic Colorectal Cancer Not Previously Treated and With Three or More Circulating Tumoral Cells (VISNU-1)
April 10, 2019 updated by: Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)
Phase III, Randomized Clinical Trial to Evaluate FOLFOX + Bevacizumab Versus FOLFOXIRI + Bevacizumab as First Line Treatment of Patients With Metastatic Colorectal Cancer Not Previously Treated and With Three or More Circulating Tumoral Cells.
The purpose of the study is to evaluate FOLFOX + bevacizumab versus FOLFOXIRI + bevacizumab as first line treatment of patients with metastatic colorectal cancer not previously treated and with three or more circulating tumoral cells.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
350
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Madrid, Spain, 28046
- Spanish Cooperative Group for Digestive Tumour Therapy
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 70 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Patient's Informed consent in written.
- Age between 18 and 70 years old.
- Eastern Cooperative Oncology group performance status (ECOG) 0-1.
- Life expectancy of at least 3 months.
- Histological confirmation of adenocarcinoma of the colon or rectum.
- To be included in the study patients should present > or equal 3 CTC in peripheral blood.
- Measurable metastatic stage IV disease with at least 1 measurable metastatic lesion following Response Evaluation Criteria In Solid Tumors (RECIST) criteria v 1.1 (non suitable for radical surgery at the inclusion time).
- Prior radiotherapy is allowed but must be completed at least 4 weeks before randomization (if applicable).
- Adequate bone marrow, liver and renal function.
- Women of childbearing potential must have a negative serum or urine pregnancy test. Postmenopausal women must have been amenorrheic for at least 12 months.Both men and women participating in this study must use adequate contraception.
- Subject must have the ability, in the opinion of the investigator, to comply with all the study procedures and follow-up examinations.
Exclusion Criteria:
- Previous chemotherapy for metastatic disease.
- Prior treatment with Bevacizumab, or Epidermal Growth Factor Reception (EGFR) inhibitors
- Any anticancer treatment (chemotherapy, hormonal treatment, radiation treatment, surgery , immunotherapy, biologic therapy or tumour embolization) within 4 weeks before randomization.
- Use of any investigational drug within 4 weeks before start the treatment
- Clinical or radiographic evidence of brain metastasis.
- Uncontrolled hypertension (systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg on repeated measurement) despite optimal medical management.
- Previous history of hypertensive encephalopathy or hypertensive crises.
- Current or history of peripheral neuropathy > or equal to 1 National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE).
- Patients classified as fragile according to criteria listed in the protocol.
- Significant cardiovascular disease (e.g. cerebrovascular accident (CVA), myocardial infarction, within 6 months before randomization). Unstable angina, congestive heart failure New York Heart Association (NYHA) ≥ class II, arrhythmia that requires treatment within 3 months before randomization.
- Significant vascular disease (e.g. aortic aneurism requiring surgical intervention, pulmonary embolic, peripheral arterial thrombosis) within 6 months before randomization.
- Previous history of significant haemorrhage /severe, within 1 month before randomization.
- Major surgery, open surgical biopsy or significant traumatic injury within 4 weeks before randomization.
- Large bore needle biopsy of a major organ within 14 days before randomization. Placement of central venous access port > or equal to 7 days before randomization is permitted
- Evidence or history of bleeding diathesis or coagulopathy.
- International Normalized Ratio (INR) > 1.5 within 14 days prior to starting study treatment. EXEMPTION: patients on full anticoagulation must have an in-range INR [usually between 2-3]. Any anticoagulation therapy must be at stable dosing prior to enrollment.
- History of previous abdominal fistula or gastrointestinal perforation within 6 months before randomization.
- Serious non-healing wound, ulcer or bone fracture.
- Acute or sub-acute of intestinal occlusion or history of intestinal inflammatory disease.
- History of uncontrolled convulsive crises.
- History of pulmonary fibrosis, acute lung disease or interstitial pneumonia.
- Chronic, actual o recent use (10 days prior first drug administration) of acetylsalicylic acic (aspirin) > 325 mg/day or clopidogrel (75mg/day) or other treatments that can cause gastrointestinal ulcer (low-dose aspirin is permitted < or equal to 325 mg/day).
- Urinary protein excretion > or equal to 2+ (dipstick). If > or equal 2 g proteinuria is detected with dipstick, a 24-hour period urine test will be performed and the result should be < or equal to 1 g/24 hours to permit the inclusion of the patient in the clinical trial.
- Known human immunodeficiency virus infection or chronic hepatitis B or C infection or other uncontrolled, severe concurrent infection .
- Current infection > or equal to Grade 2 (NCI-CTCAE).
- Any previous or concurrent cancer different to colorectal carcinoma within 5 years before to start the treatment. Subjects with successfully treated, non-invasive cancers, including cervical cancer in situ, basal cell carcinoma will be allowed to participate in the clinical trial. Or those cancer treated with curative intention without disease evidence in the last 5 years at least.
- Known or suspected allergy or hypersensitivity to any component of Bevacizumab, oxaliplatin, irinotecan, or 5-FU/LV.
- Any medical, psychological, or social condition that may interfere with the subject's participation in the study or evaluation of the study results.
- Any psychological, familial or geographic situation that interferes in the adequate follow.up and adherence to the study protocol.
- Women who are pregnant or breast-feeding.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Control
modified FOLFOX6 + bevacizumab
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Experimental: Experimental
FOLFOXIRI+bevacizumab
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Progression free survival (PFS)
Time Frame: 5 years
|
5 years
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Overall survival (OS)
Time Frame: 5 years
|
5 years
|
Adverse events
Time Frame: 5 years
|
5 years
|
Response rate (RR)
Time Frame: 5 years
|
5 years
|
Radical Resection (R0) surgery rate
Time Frame: 5 years
|
5 years
|
Circulating Tumour Cells (CTC) count basal and correlate to PFS, OS, RR
Time Frame: 5 years
|
5 years
|
Correlation of RAS, BRAF and PI3K mutations and clinical anti-tumour activity outcome ( PFS, OS, RR)
Time Frame: 5 years
|
5 years
|
Correlation of molecular status of bio markers related to the cellular and tumoral reproduction and/or mode of action and clinical anti-tumour activity outcome ( PFS, OS, RR)
Time Frame: 5 years
|
5 years
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
July 1, 2012
Primary Completion (Actual)
November 1, 2018
Study Completion (Actual)
November 1, 2018
Study Registration Dates
First Submitted
June 13, 2012
First Submitted That Met QC Criteria
July 12, 2012
First Posted (Estimate)
July 13, 2012
Study Record Updates
Last Update Posted (Actual)
April 11, 2019
Last Update Submitted That Met QC Criteria
April 10, 2019
Last Verified
April 1, 2019
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms
- Neoplasms by Site
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Colonic Diseases
- Intestinal Diseases
- Intestinal Neoplasms
- Rectal Diseases
- Colorectal Neoplasms
- Physiological Effects of Drugs
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Bevacizumab
Other Study ID Numbers
- TTD-12-01
- 2012-000846-37 (EudraCT Number)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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