Study of FOLFIRI Plus Bevacizumab in Colorectal Cancer Patients

NCT00354978 | Completed Phase 2 Results

• 1 other identifier: 2004-0614
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 2

Brief Summary

Objectives:

1. 1.To estimate progression-free survival (PFS) at 12 months in subjects with metastatic colorectal cancer who receive FOLFIRI \[folinic acid (leucovorin or LV), 5-Fluorouracil (5-FU), irinotecan) plus bevacizumab as first line treatment.
2. 2.To determine the objective response rate and the duration of objective response in this population.
3. 3.To assess overall survival (OS) in this population.
4. 4.To measure the effect of treatment on intratumoral blood volume and microvascular permeability by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in consenting patients in whom it is technically feasible.
5. 5.To correlate plasma proteomics with response.
6. 6.To assess the safety of this regimen.

Conditions

Colorectal Cancer

Keywords

Colorectal Cancer; FOLFIRI; Irinotecan; CPT-11; Leucovorin; LV; Folinic Acid; Fluorouracil; 5-FU; Adrucil; Efudex; Bevacizumab; Avastin; Anti-VEGF monoclonal antibody; rhuMAb-VEGF

Outcome Measures

Primary Outcomes (1)

• Median Progression-free Survival (PFS)

  PFS is defined as the duration of time from start of treatment to time of disease progression using Kaplan-Meier median PFS time.

  From baseline until first documented progression or death from any cause, whichever came first, assessed up to 75 months

Study Arms (1)

FOLFIRI plus Bevacizumab

EXPERIMENTAL

FOLFIRI \[folinic acid (leucovorin) 400 mg/m\^2 by vein (IV) Day 1; 5-FU 400 mg/m\^2 IV injection Day 1 immediately followed by 2.4 g/m\^2 IV over 46 hours over Days 1-3; Irinotecan 180 mg/m\^2 IV on Day 1\] + Bevacizumab 5 mg/kg over 90 minutes on Day 1 administered alone then 5 mg/kg IV on Day 1 of 14 day cycle.

Drug: 5-Fluorouracil; Drug: Bevacizumab; Drug: Leucovorin; Drug: Irinotecan

Interventions

5-Fluorouracil DRUG

400 mg/m\^2 injection by vein Day 1 of 14 day cycle immediately after completion of leucovorin infusion. 2.4 g/m\^2 by vein over 46 hours over Days 1-3 of 14 day cycle immediately after completion of 400 mg/m\^2 injection.

Also known as: F of FOLFIRI, 5-FU, Adrucil, Efudex

FOLFIRI plus Bevacizumab

Bevacizumab DRUG

5 mg/kg over 90 minutes on Day 1 of first 14 day cycle as initial dose, administered alone without other drugs. 5 mg/kg by vein on Day 1 of 14 day cycle.

Also known as: Avastin, Anti-VEGF monoclonal antibody, rhuMAb-VEGF

FOLFIRI plus Bevacizumab

Leucovorin DRUG

400 mg/m\^2 over 2-4 minutes by vein on Day 1 of 14 day cycle.

Also known as: FOL of FOLFIRI, LV, folinic acid

FOLFIRI plus Bevacizumab

Irinotecan DRUG

180 mg/m\^2 by vein over 90 minutes on Day 1 of 14 day cycle.

Also known as: IRI of FOLFIRI, CPT-11

FOLFIRI plus Bevacizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient must have histologically or cytologically confirmed colorectal adenocarcinoma with metastatic disease documented on diagnostic imaging studies.
• Patient must have measurable lesions as defined by modified Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Patients who agree to undergo the optional Dynamic contrast enhanced-magnetic resonance imaging (DCE-MRI) studies must have a metastatic liver lesion that is \> 2 cm.
• Patient has not previously received chemotherapy for metastatic disease.
• Patient may have received adjuvant therapy for primary colorectal cancer provided that at least 6 months have elapsed from the time the adjuvant therapy was concluded and recurrent disease was documented.
• Written informed consent obtained.
• Age greater than/equal to 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Patients must have adequate organ and marrow function as defined below: · Absolute neutrophil count (ANC) greater than/equal to 1,500/mm3; platelets greater than/equal to 100,000/ mm3; hemoglobin greater than/equal to 9 gm/dL (may be transfused to maintain or exceed this level); total bilirubin less than/equal to 1.5 within institutional upper limit of normal (IULN); aspartate aminotransferase (AST or SGOT)/alanine aminotransferase (ALT or SGPT) less than/equal to 2.5 times IULN, or less than/equal to 5 times IULN if known liver metastases; serum creatinine less than/equal to 1.5 times IULN
• Patients must have an International Normalized Ratio (INR) less than/equal to 1.5 and a Partial thromboplastin time (PTT) less than/equal to IULN
• Patients with history of hypertension must be well-controlled (blood pressure less than/equal to 150/100), on a stable regimen of anti-hypertensive therapy.

You may not qualify if:

• Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental therapeutic drug study other than this protocol.
• Prior full field radiotherapy less than/equal to 4 weeks or limited field radiotherapy less than/equal to 2 weeks prior to treatment.
• History or presence of central nervous system metastases.
• Female patients who are pregnant or lactating or men and women of reproductive potential not willing to employ an effective method of birth control during treatment and for 3 months after discontinuing study treatment.
• A history of prior treatment with bevacizumab or other agents targeting Vascular endothelial growth factor (VEGF).
• Known dihydropyrimidine dehydrogenase deficiency.
• Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to bevacizumab, irinotecan, 5-FU, or leucovorin.
• Serious non-healing wound, ulcer, or active bone fracture.
• Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to Day 0; anticipation of need for major surgical procedure during the course of the study.
• Fine needle aspirations or core biopsies within 7days prior to Day 0.
• For patients who agree to Optional DCE-MRI studies: Cardiac pacemaker, neurostimulator, metal implants other than those specifically approved as safe for use in MR scanners at the magnetic field strength used for these studies, claustrophobia, obesity (weight exceeding equipment limits).
• Current or recent use of full-dose warfarin (except as required to maintain patency of preexisting, permanent indwelling IV catheters) for subjects receiving warfarin, INR should be \< 1.5). Patients may have prophylactic use of low molecular weight heparin, however therapeutic use of heparin or low molecular weight heparin is not acceptable.
• Evidence of bleeding diathesis or coagulopathy.
• Patients with a history of another primary malignancy less than/equal to 5 years, with the exception of non-melanoma skin cancer, and carcinoma in situ of uterine cervix.
• History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to Day 0, unless affected area has been removed surgically.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Genentech, Inc.: collaborator
• Pfizer: collaborator

Study Sites (2)

Lyndon Baines Johnson General Hospital

Houston, Texas, 77030, United States

Location

UT MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• UT MD Anderson Cancer Center website

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Fluorouracil; Bevacizumab; Leucovorin; Irinotecan

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Camptothecin; Alkaloids

Results Point of Contact

• Title: Scott Kopetz, MD Associate Professor
• Organization: UT MD Anderson Cancer Center

mjlim@mdanderson.org

713-792-2828

Study Officials

• Scott Kopetz, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 18, 2006
• First Posted: July 20, 2006
• Study Start: January 1, 2005
• Primary Completion: March 1, 2011
• Study Completion: March 1, 2011
• Last Updated: October 21, 2011
• Results First Posted: October 21, 2011

Record last verified: 2011-09

Locations

US (2)