NCT01640444

Brief Summary

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

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
240

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Jul 2012

Longer than P75 for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 13, 2012

Completed
18 days until next milestone

Study Start

First participant enrolled

July 1, 2012

Completed
12 days until next milestone

First Posted

Study publicly available on registry

July 13, 2012

Completed
6.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2018

Completed
Last Updated

April 11, 2019

Status Verified

August 1, 2018

Enrollment Period

6.3 years

First QC Date

June 13, 2012

Last Update Submit

April 10, 2019

Conditions

Colorectal Cancer Metastatic

Keywords

colorectal carcinomaBRAF and PIK3KFOLFIRI -Bevacizumab -Cetuximabcirculating tumor cells

Outcome Measures

Primary Outcomes (1)

  • progression free survival (PFS)

    5 years

Secondary Outcomes (6)

  • Overall survival (OS)

    5 years

  • Response rate (RR)

    5 years

  • Radical Resection (R0) surgery rate

    5 years

  • CTC count basal and correlate to PFS, OS, RR

    5 years

  • Adverse events

    5 years

  • +1 more secondary outcomes

Study Arms (2)

A

EXPERIMENTAL

FOLFIRI+bevacizumab

Drug: FOLFIRI + bevacizumab

B

EXPERIMENTAL

FOLFIRI + cetuximab

Drug: FOLFIRI + cetuximab

Interventions

FOLFIRI + bevacizumabDRUG

* 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).

A
FOLFIRI + cetuximabDRUG

* 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).

B

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patient's Informed consent in written.
  • Age between 18-70 years old.
  • ECOG 0-1.
  • Life expectancy of at least 3 months.
  • Histological confirmation of adenocarcinoma of the colon or rectum.
  • 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.
  • 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.

You may not qualify if:

  • Previous chemotherapy for metastatic disease.
  • Prior treatment with Bevacizumab, or 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 NCICTCAE.
  • Patients classified as fragile according to criteria listed in the protocol.
  • 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.
  • 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.
  • +14 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Spanish Cooperative Group for Digestive Tumour Therapy

Madrid, 28046, Spain

Location

Related Publications (3)

  • Valladares-Ayerbes M, Toledano-Fonseca M, Grana B, Jimenez-Fonseca P, Pulido-Cortijo G, Gil S, Sastre J, Salud A, Rivera F, Salgado M, Garcia-Alfonso P, Lopez Lopez R, Guillen-Ponce C, Rodriguez-Ariza A, Vieitez JM, Diaz-Rubio E, Aranda E; Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD). Associations of blood RNA biomarkers and circulating tumour cells in patients with previously untreated metastatic colorectal cancer. BMC Cancer. 2025 Apr 21;25(1):743. doi: 10.1186/s12885-025-14098-9.

    PMID: 40259317DERIVED

  • Jimenez-Fonseca P, Sastre J, Garcia-Alfonso P, Gomez-Espana MA, Salud A, Gil S, Rivera F, Reina JJ, Quintero G, Valladares-Ayerbes M, Safont MJ, La Casta A, Robles-Diaz L, Garcia-Paredes B, Lopez Lopez R, Guillot M, Gallego J, Alonso-Orduna V, Diaz-Rubio E, Aranda E; Spanish Cooperative Group for the Treatment of Digestive Tumors (TTD). Association of Circulating Tumor Cells and Tumor Molecular Profile With Clinical Outcomes in Patients With Previously Untreated Metastatic Colorectal Cancer: A Pooled Analysis of the Phase III VISNU-1 and Phase II VISNU-2 Randomized Trials. Clin Colorectal Cancer. 2023 Jun;22(2):222-230. doi: 10.1016/j.clcc.2023.02.004. Epub 2023 Feb 21.

    PMID: 36944559DERIVED

  • Sastre J, Orden V, Martinez A, Bando I, Balbin M, Bellosillo B, Palanca S, Peligros Gomez MI, Mediero B, Llovet P, Moral VM, Vieitez JM, Garcia-Alfonso P, Calle SG, Ortiz-Morales MJ, Salud A, Quintero G, Lopez C, Diaz-Rubio E, Aranda E; Spanish Cooperative Group for the Treatment of Digestive Tumors (TTD). Association Between Baseline Circulating Tumor Cells, Molecular Tumor Profiling, and Clinical Characteristics in a Large Cohort of Chemo-naive Metastatic Colorectal Cancer Patients Prospectively Collected. Clin Colorectal Cancer. 2020 Sep;19(3):e110-e116. doi: 10.1016/j.clcc.2020.02.014. Epub 2020 Mar 6.

    PMID: 32278676DERIVED

Related Links

MeSH Terms

Conditions

Colorectal NeoplasmsHereditary Sensory and Autonomic NeuropathiesNeoplastic Cells, Circulating

Interventions

BevacizumabCetuximab

Condition Hierarchy (Ancestors)

Intestinal NeoplasmsGastrointestinal NeoplasmsDigestive System NeoplasmsNeoplasms by SiteNeoplasmsDigestive System DiseasesGastrointestinal DiseasesColonic DiseasesIntestinal DiseasesRectal DiseasesNervous System MalformationsNervous System DiseasesHeredodegenerative Disorders, Nervous SystemNeurodegenerative DiseasesPolyneuropathiesPeripheral Nervous System DiseasesNeuromuscular DiseasesCongenital AbnormalitiesCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesGenetic Diseases, InbornNeoplasm MetastasisNeoplastic ProcessesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Officials

  • Eduardo Díaz-Rubio, MD-PhD

    Hospital San Carlos, Madrid

    STUDY CHAIR

  • Enrique Aranda, MD-PhD

    Hospital Reina Sofía

    STUDY CHAIR

  • Javier Sastre, MD-PhD

    Hospital San Carlos, Madrid

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 13, 2012

First Posted

July 13, 2012

Study Start

July 1, 2012

Primary Completion

November 1, 2018

Study Completion

November 1, 2018

Last Updated

April 11, 2019

Record last verified: 2018-08

Locations

ES(1)