Influence of BRAF and PIK3K Status on the Efficacy of 5-Fluorouracil/Leucovorin/Oxaliplatin (FOLFIRI) Plus Bevacizumab or Cetuximab in Patients With RAS Wild-type Metastatic Colorectal Carcinoma and < 3 Circulating Tumor Cells (CTC) (VISNU-2)

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Spanish Cooperative Group for Digestive Tumour Therapy (TTD)
Sponsor:
Collaborator:
Roche Pharma AG
Information provided by (Responsible Party):
Spanish Cooperative Group for Digestive Tumour Therapy (TTD)
ClinicalTrials.gov Identifier:
NCT01640444
First received: June 13, 2012
Last updated: March 26, 2014
Last verified: March 2014
  Purpose

The purpose of the study is to explore the influence of BRAF and PIK3K status on the efficacy of FOLFIRI plus Bevacizumab or Cetuximab, as first line therapy of patients with RAS wild-type metastatic colorectal carcinoma and < 3 circulating tumor cells


Condition Intervention Phase
Colorectal Cancer Metastatic
Drug: FOLFIRI + bevacizumab
Drug: FOLFIRI + cetuximab
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Phase II Study to Explore the Influence of BRAF and PIK3K Status on the Efficacy of FOLFIRI Plus Bevacizumab or Cetuximab, as First Line Therapy of Patients With RAS Wild-type Metastatic Colorectal Carcinoma and < 3 Circulating Tumor Cells

Resource links provided by NLM:


Further study details as provided by Spanish Cooperative Group for Digestive Tumour Therapy (TTD):

Primary Outcome Measures:
  • progression free survival (PFS) [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival (OS) [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Response rate (RR) [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Radical Resection (R0) surgery rate [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • CTC count basal and correlate to PFS, OS, RR [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • Adverse events [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 240
Study Start Date: July 2012
Estimated Study Completion Date: June 2017
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
FOLFIRI+bevacizumab
Drug: FOLFIRI + bevacizumab
  • Bevacizumab 5 mg/kg iv, followed by
  • Irinotecan 180 mg/m2 iv administered over a period of 30-90 minutes, followed by
  • Leucovorin (LV) 400 mg/m2 iv administered over a period of 2 hours, followed by
  • 5-FU 400 mg/m2 iv bolus, followed by
  • 5-FU 2,400 mg/m2 for 46 h continuous infusion. This treatment will start on day 1 and will be repeated every 2 weeks (1 cycle).
Experimental: B
FOLFIRI + cetuximab
Drug: FOLFIRI + cetuximab
  • Cetuximab in an initial 120-minute infusion on day 1 of 400 mg/m2, followed by 60-minute infusions of cetuximab at a dose of 250 mg/m2, once weekly
  • FOLFIRI:

    • Irinotecan 180 mg/m2 iv administered over a period of 30-90 minutes, followed by
    • Leucovorin (LV) 400 mg/m2 iv administered over a period of 2 hours, followed by
    • 5-FU 400 mg/m2 iv bolus, followed by
    • 5-FU 2,400 mg/m2 for 46 h continuous infusion FOLFIRI will be given after the cetuximab infusion on day 1 of each period (every 2 weeks: 1 cycle).

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patient's Informed consent in written.
  2. Age between 18-70 years old.
  3. ECOG 0-1.
  4. Life expectancy of at least 3 months.
  5. Histological confirmation of adenocarcinoma of the colon or rectum.
  6. Sample of tumour tissue available for evaluation of genes RAS, BRAF and PI3K. To be included in the study patients should present < 3 CTC in peripheral blood and RAS wild-type present in the sample of tumor tissue.
  7. Measurable metastatic stage IV disease with at least 1 measurable metastatic lesion following RECIST criteria v 1.1 (non suitable for radical surgery at the inclusion time).
  8. Prior radiotherapy is allowed but must be completed at least 4 weeks before randomization (if applicable).
  9. Adequate bone marrow, liver and renal function.
  10. 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.
  11. Subject must have the ability, in the opinion of the investigator, to comply with all the study procedures and follow-up examinations.

Exclusion Criteria:

  1. Previous chemotherapy for metastatic disease.
  2. Prior treatment with Bevacizumab, or EGFR inhibitors
  3. Any anticancer treatment (chemotherapy, hormonal treatment, radiation treatment, surgery , immunotherapy, biologic therapy or tumour embolization) within 4 weeks before randomization.
  4. Use of any investigational drug within 4 weeks before start the treatment.
  5. Clinical or radiographic evidence of brain metastasis.
  6. Uncontrolled hypertension (systolic blood pressure >150 mmHg and/or diastolic blood pressure >100 mmHg on repeated measurement) despite optimal medical management.
  7. Previous history of hypertensive encephalopathy or hypertensive crises.
  8. Current or history of peripheral neuropathy > or equal to 1 NCICTCAE.
  9. Patients classified as fragile according to criteria listed in the protocol.
  10. Significant cardiovascular disease (e.g. AVC, 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.
  11. Significant vascular disease (e.g. aortic aneurism requiring surgical intervention, pulmonary embolic, peripheral arterial thrombosis) within 6 months before randomization.
  12. Previous history of significant haemorrhage /severe, within 1 month before randomization.
  13. Major surgery, open surgical biopsy or significant traumatic injury within 4 weeks before randomization.
  14. 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.
  15. Evidence or history of bleeding diathesis or coagulopathy.
  16. 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 enrolment.
  17. History of previous abdominal fistula or gastrointestinal perforation within 6 months before randomization.
  18. Serious non-healing wound, ulcer or bone fracture.
  19. Acute or sub-acute of intestinal occlusion or history of intestinal inflammatory disease.
  20. History of uncontrolled convulsive crises.
  21. History of pulmonary fibrosis, acute lung disease or interstitial pneumonia.
  22. 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).
  23. 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
  24. Known human immunodeficiency virus infection or chronic hepatitis B or C infection or other uncontrolled, severe concurrent infection .
  25. Current infection > or equal to Grade 2 (NCI-CTCAE).
  26. 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
  27. Known or suspected allergy or hypersensitivity to any component of bevacizumab, cetuximab, irinotecan, or 5-FU/LV.
  28. Any medical, psychological, or social condition that may interfere with the subject's participation in the study or evaluation of the study results.
  29. Any psychological, familial or geographic situation that interferes in the adequate follow-up and adherence to the study protocol.
  30. Women who are pregnant or breast-feeding.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01640444

Contacts
Contact: Inmaculada Ruiz de Mena, PhD 00 34 91 378 82 75 ttd@ttdroup.org

Locations
Spain
Spanish Cooperative Group for Digestive Tumour Therapy Recruiting
Madrid, Spain, 28046
Contact: Inmaculada Ruiz de Mena, PhD    00 34 91 378 82 75    ttd@ttdgroup.org   
Sponsors and Collaborators
Spanish Cooperative Group for Digestive Tumour Therapy (TTD)
Roche Pharma AG
Investigators
Study Chair: Eduardo Díaz-Rubio, MD-PhD Hospital Clínico San Carlos
Study Chair: Enrique Aranda, MD-PhD Hospital Reina Sofía
Study Chair: Javier Sastre, MD-PhD Hospital Clínico San Carlos
  More Information

Additional Information:
No publications provided

Responsible Party: Spanish Cooperative Group for Digestive Tumour Therapy (TTD)
ClinicalTrials.gov Identifier: NCT01640444     History of Changes
Other Study ID Numbers: TTD-12-02, 2012-000840-90
Study First Received: June 13, 2012
Last Updated: March 26, 2014
Health Authority: Spain: Ministry of Health

Keywords provided by Spanish Cooperative Group for Digestive Tumour Therapy (TTD):
colorectal carcinoma
BRAF and PIK3K
FOLFIRI -Bevacizumab -Cetuximab
circulating tumor cells

Additional relevant MeSH terms:
Carcinoma
Colorectal Neoplasms
Neoplastic Cells, Circulating
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Neoplasm Metastasis
Neoplastic Processes
Pathologic Processes
Leucovorin
Bevacizumab
Cetuximab
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Inhibitors

ClinicalTrials.gov processed this record on July 22, 2014