Second-Line Combination Chemotherapy With or Without Bevacizumab in Treating Patients With Metastatic Colorectal Cancer Who Have Received First-Line Chemotherapy and Bevacizumab

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2009 by Gruppo Oncologico del Nord-Ovest.
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by (Responsible Party):
Gruppo Oncologico del Nord-Ovest
ClinicalTrials.gov Identifier:
NCT00720512
First received: July 19, 2008
Last updated: October 12, 2012
Last verified: July 2009
  Purpose

RATIONALE: Drugs used in chemotherapy, such as irinotecan, oxaliplatin, leucovorin, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. It is not yet known whether combination chemotherapy is more effective with or without bevacizumab in treating metastatic colorectal cancer.

PURPOSE: This randomized phase III trial is studying second-line combination chemotherapy to see how well it works compared with or without bevacizumab in treating patients with metastatic colorectal cancer who have received first-line chemotherapy and bevacizumab.


Condition Intervention Phase
Colorectal Cancer
Biological: bevacizumab
Drug: fluorouracil
Drug: irinotecan hydrochloride
Drug: leucovorin calcium
Drug: oxaliplatin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: AN OPEN-LABEL, MULTICENTER, RANDOMIZED PHASE III STUDY OF SECOND-LINE CHEMOTHERAPY WITH OR WITHOUT BEVACIZUMAB IN METASTATIC COLORECTAL CANCER PATIENTS WHO HAVE RECEIVED FIRST-LINE CHEMOTHERAPY PLUS BEVACIZUMAB.

Resource links provided by NLM:


Further study details as provided by Gruppo Oncologico del Nord-Ovest:

Primary Outcome Measures:
  • Progression-free survival [ Time Frame: last progression of the last patient ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Time Frame: the end of the stady ] [ Designated as safety issue: No ]
  • Response rate [ Time Frame: last visit of the last patient ] [ Designated as safety issue: No ]
  • Safety [ Time Frame: the end of the study ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 262
Study Start Date: June 2008
Estimated Study Completion Date: March 2014
Estimated Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm I
Patients receive either irinotecan hydrochloride over 1 hour or oxaliplatin over 1 hour on day 1. Patients also receive leucovorin calcium IV over 2 hours and fluorouracil IV over 46 hours continuously beginning on day 1. Treatment repeats every 2 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Drug: fluorouracil
Given IV
Drug: irinotecan hydrochloride
Given IV
Drug: leucovorin calcium
Given IV
Drug: oxaliplatin
Given IV
Experimental: Arm II
Patients receive combination chemotherapy as in arm I and bevacizumab IV on day 1. Treatment repeats every 2 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.
Biological: bevacizumab
Given IV
Drug: fluorouracil
Given IV
Drug: irinotecan hydrochloride
Given IV
Drug: leucovorin calcium
Given IV
Drug: oxaliplatin
Given IV

Detailed Description:

OBJECTIVES:

Primary

  • To compare the progression-free survival of second-line chemotherapy with or without bevacizumab in patients with metastatic colorectal cancer who have received first-line chemotherapy with bevacizumab.

Secondary

  • To compare the overall survival, response rate, and safety profile of second-line chemotherapy of these regimens in these patients.
  • To conduct pharmacogenomics assessment of candidate variants in the VEGF gene and evaluate their association with progression-free survival and other study outcomes.

OUTLINE: This is a multicenter study. Patients are stratified according to participating center, ECOG performance status (0 vs 1-2), disease-free interval from the last administration of first-line chemotherapy for metastatic disease (≤ 3 months vs > 3 months), and type of second-line chemotherapy (irinotecan hydrochloride, leucovorin calcium, and fluorouracil [FOLFIRI] vs oxaliplatin, leucovorin calcium, and fluorouracil [mFOLFOX-6]). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive either irinotecan hydrochloride over 1 hour or oxaliplatin over 1 hour on day 1. Patients also receive leucovorin calcium IV over 2 hours and fluorouracil IV over 46 hours continuously beginning on day 1.
  • Arm II: Patients receive combination chemotherapy as in arm I and bevacizumab IV on day 1.

Treatment in both arms repeats every 2 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Existing formalin-fixed paraffin-embedded tumor tissue samples are assessed for pharmacogenomics and markers predictive of response, resistance to, or toxicity from bevacizumab. Samples are analyzed via RT-PCR, array comparative genomic hybridization, fluorescence in situ hybridization, sequencing of candidate genes, and immunohistochemistry.

After completion of study treatment, patients are followed for 1 year.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed colorectal adenocarcinoma

    • Metastatic or unresectable disease
  • Progressive disease based on the following criteria:

    • Progression during or after first-line chemotherapy for metastatic disease, including any of the following:

      • Fluoropyrimidine-based monotherapy with bevacizumab
      • Fluoropyrimidine and irinotecan hydrochloride-based doublet with bevacizumab
      • Fluoropyrimidine and oxaliplatin-based doublet with bevacizumab
    • Progression after more than 3 months from the last administration of first-line chemotherapy for metastatic disease with a fluoropyrimidine, irinotecan hydrochloride, and oxaliplatin triplet (FOLFOXIRI) with bevacizumab to which the patient had previously responded
  • Measurable disease, as assessed by RECIST criteria
  • No prior or concurrent CNS metastasis

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Life expectancy > 3 months
  • ANC ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Hemoglobin ≥ 9 g/dL
  • INR ≤ 1.5 times upper limit of normal (ULN)
  • aPTT ≤ 1.5 ULN
  • Serum bilirubin ≤ 1.5 times ULN
  • AST and ALT ≤ 2.5 times ULN (< 5 times ULN if liver metastases present)
  • Alkaline phosphatase ≤ 2.5 times ULN (< 5 times ULN if liver metastases present)
  • Serum creatinine ≤ 1.5 times ULN
  • Proteinuria < 2+ OR protein ≤ 1g by 24-hour urine
  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • No bowel obstruction or subobstruction
  • No history of inflammatory enteropathy
  • No prior extensive intestinal resection (i.e., > hemicolectomy or extensive small intestine resection with chronic diarrhea)
  • No symptomatic peripheral neuropathy > grade 2
  • No active uncontrolled infection
  • No active disseminated intravascular coagulation
  • No prior or concurrent malignancy, except for curatively treated basal cell and squamous cell carcinoma of the skin, or in situ carcinoma of the cervix
  • No clinically significant cardiovascular disease, including any of the following:

    • Cerebrovascular accident within the past 6 months
    • Myocardial infarction within the past 6 months
    • Unstable angina
    • NYHA class II-IV chronic heart failure
    • Uncontrolled arrhythmia
  • No uncontrolled hypertension
  • No thromboembolic or hemorrhagic events within the past 6 months
  • No evidence of bleeding diathesis or coagulopathy
  • No serious, non healing wound/ulcer or serious bone fracture
  • No significant traumatic injury within the past 28 days

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • At least 6 weeks since prior radiotherapy
  • At least 4 weeks since prior surgery
  • No prior first-line chemotherapy for metastatic disease without bevacizumab
  • No prior cetuximab or other investigational agents
  • More than 28 days since prior open biopsy
  • More than 28 days since prior and no concurrent major surgical procedure
  • No concurrent therapeutic anticoagulation, antiplatelet agents, or NSAID with anti-platelet activity

    • Acetylsalicylic acid ≤ 325 mg/day allowed
  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: NCT00720512

Locations
Italy
Universita Politecnica Delle Marche
Ancona, Italy, 60100
Azienda Usl 8 Arezzo
Arezzo, Italy, 52100
Ospedale degli Infermi - ASL 12
Biella, Italy, 13900
A. Perrino Hospital
Brindisi, Italy, 72100
Azienda Ospedaliera S. Elia
Caltanissetta, Italy, 93100
Ospedale Santa Croce
Cuneo, Italy, 12100
Ospedale San Giuseppe
Empoli, Italy, 50053
Ospedale E. Profili
Fabriano, Italy, 60044
Ospedale Civile S. Croce
Fano, Italy, 61032
Azienda Ospedaliero Careggi
Florence, Italy, 50139
Azienda Ospedaliera di Firenze
Florence, Italy, 50011
Istituto Nazionale per la Ricerca sul Cancro
Genoa, Italy, 16132
Ospendale S. Andrea EST
La Spezia, Italy, 19100
Azienda Ospedaliera Vito Fazzi
Lecce, Italy, 73100
Azienda USL12 Versilia
Lido di Camaiore, Italy, 55043
Ospedale Campo Di Marte Lucca
Lucca, Italy, 55100
Azienda Ospedaliera Maggiore Della Carita
Novara, Italy, 28100
Azienda Ospedaliera Pisana
Pisa, Italy, 56126
Arcispedale S. Maria Nuova
Reggio Emilia, Italy, 42100
Dipartimento Oncologico
Siena, Italy, 53100
Azienda Ospedaliera Universitaria Senese
Siena, Italy, 53100
Sponsors and Collaborators
Gruppo Oncologico del Nord-Ovest
Investigators
Principal Investigator: Alfredo Falcone, MD Presidio Ospedaliero di Livorno
  More Information

Additional Information:
No publications provided

Responsible Party: Gruppo Oncologico del Nord-Ovest
ClinicalTrials.gov Identifier: NCT00720512     History of Changes
Other Study ID Numbers: CDR0000598567, GONO-BEBYP-ASL607LIOM03, GONO-AIFA - FARM5C4FB4, EUDRACT:2007-002886-11
Study First Received: July 19, 2008
Last Updated: October 12, 2012
Health Authority: Italy: Agenzia Italiana del Farmaco (AIFA)

Keywords provided by Gruppo Oncologico del Nord-Ovest:
adenocarcinoma of the colon
adenocarcinoma of the rectum
recurrent colon cancer
recurrent rectal cancer
stage IV colon cancer
stage IV rectal cancer
stage III rectal cancer
stage III colon cancer

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Fluorouracil
Oxaliplatin
Irinotecan
Bevacizumab
Camptothecin
Leucovorin
Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Vitamin B Complex
Vitamins
Micronutrients

ClinicalTrials.gov processed this record on August 01, 2014