Safety and Efficacy Study Using Bevacizumab, Capecitabine and Oxaliplatin for Colorectal Cancer

This study has been completed.
Sponsor:
Collaborator:
Genentech, Inc.
Information provided by (Responsible Party):
Nathan Bahary, MD, University of Pittsburgh
ClinicalTrials.gov Identifier:
NCT00177307
First received: September 12, 2005
Last updated: December 18, 2013
Last verified: December 2013
  Purpose

This is a Phase II study of the drug combination of Oxaliplatin, Avastin and capecitabine. This is an open-label study.


Condition Intervention Phase
Cancer
Drug: Bevacizumab
Drug: Capecitabine
Drug: Oxaliplatin
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of the A-ICOX Regimen Consisting of Bevacizumab (Avastinâ), Intermittent Dose Capecitabine (Xelodaâ) and Oxaliplatin (Eloxatinâ) in Patients With Untreated Advanced Colorectal Cancer

Resource links provided by NLM:


Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • To assess the progression free survival (PFS) of patients with previously untreated advanced CRC. [ Time Frame: survival ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To measure response rate, duration of response for responding patients, overall survival time and 1, 2 and 3 year survival of patients and to characterize the quantitative and qualitative toxicities [ Time Frame: survival ] [ Designated as safety issue: No ]

Enrollment: 45
Study Start Date: January 2005
Study Completion Date: February 2012
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Oxaliplatin, Capecitabine, and Bevacizumab Drug: Bevacizumab
Bevacizumab 5 mg/kg by 90-30 minute IV infusion IV q 2 weekly Until disease progression or unacceptable toxicity
Other Names:
  • Capecitabine 2500 mg/m2/d in two divided doses
  • (May be 2000 or 3000 mg/m2/d after interim analysis) Days 1-8, every 2 weeks Until disease progression or unacceptable toxicity
  • Oxaliplatin 85 mg/m2 IV q 2 weekly Until disease progression, unacceptable toxicity,
  • or Grade 3 neuropathy or cumulative dose of 1200 mg/m2
Drug: Capecitabine
Capecitabine will be administered orally at twice daily 1250 mg/m2 (equivalent to a total daily dose of 2500 mg/m2) as intermittent therapy (1 week of treatment followed by one week without treatment) and this cycle repeated every 14 days. The first dose of capecitabine will be given on day 1 of each cycle as evening dose and the last dose will be given on day 8 as morning dose (for a total of 14 single doses per cycle).
Drug: Oxaliplatin
Oxaliplatin will be administered at the dose of 85 mg/m2 given as a 2-hour intravenous infusion on day 1 of a two-week cycle, prior to the first dose of capecitabine

Detailed Description:

Ongoing clinical trials are now evaluating the addition of bevacizumab to standard chemotherapeutic regimens for colorectal cancer such as FOLFOX or FOLFIRI. In these studies the addition of bevacizumab has been safe and has not resulted in significantly increased toxicity. Our proposed regimen has the advantage of being easily administered in the outpatient setting, with potential for enhanced activity and needs to be evaluated in a clinical trial.

The patterns of care for CRC have shifted, IFL previously the standard of care, is now proven to be an inferior regimen compared to FOLFOX4. (8) The recent FDA approval in February 2004 of bevacizumab for first line therapy, which states that bevacizumab is an approved agent in combination with a 5-FU regimen, gives no clear guidelines as to the "best regimen". This is an issue that needs to be evaluated rapidly in clinical trials, and it is clear that a combination of 5-FU or capecitabine with oxaliplatin and bevacizumab is one of the most active and well-tolerated regimens. The optimum sequence, schedule and doses needs to determined in clinical trials.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • advanced, surgically unresectable CRC
  • measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension(histological confirmation of adenocarcinoma of the colon or rectum.

ECOG performance status of 0, 1, or 2 Estimated life expectancy of at least 12 weeks.

  • chemotherapy prior to the diagnosis of metastatic disease. The chemotherapy regimen must not have included oxaliplatin or bevacizumab. No prior therapy for metastatic disease is permitted.
  • Evidence of adequate organ function, including:
  • Evidence of adequate hepatic function,
  • Evidence of adequate renal function INR <1.5 x ULN (unless taking warfarin in which case it must be in the therapeutic range). Patients on warfarin are allowed to participate.
  • Absence of proteinuria on urine analysis· Patients with a history of prior non-colorectal malignancies are eligible if they have been disease-free for at least 5 years prior to study entry and are deemed by the physician to be at low risk for recurrence. Patients with the following cancers are eligible if diagnosed and treated within the past 5 years: melanoma in situ, and basal cell and squamous cell carcinoma of the skin.
  • Age > 18 yrs.

Exclusion Criteria:

  • Any systemic therapy administered for metastatic or locally recurrent disease. Patients who are considered candidates for surgical resection of metastatic and/or locally advanced disease.
  • Any histology other than adenocarcinoma of the colon or rectum.
  • Pregnancy or lactation at the time of patient entry or women of childbearing potential with no pregnancy test. Eligible patients of reproductive potential (both sexes) must agree to use adequate contraceptive methods during and for 6 months after study therapy.
  • Serious concomitant medical conditions that, in the opinion of the investigator, would compromise the safety of the patient or compromise the patient's ability to complete the study.
  • General Medical Concerns History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that might affect the interpretation of the results of the study or render the subject at high risk from treatment complications.
  • Serious, uncontrolled, concurrent infection.
  • Lack of physical integrity of the upper gastrointestinal tract or malabsorption syndrome.
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, or anticipation of need for major surgical procedure during the course of the study; fine needle aspirations or core biopsies within 7 days prior to Day 0.
  • Proteinuria at baseline or clinically significant impairment of renal function.
  • Serious, non healing wound, ulcer, or bone fracture
  • Subjects who can not take oral medication
  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: NCT00177307

Locations
United States, Pennsylvania
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, United States, 15232
Sponsors and Collaborators
University of Pittsburgh
Genentech, Inc.
Investigators
Principal Investigator: Nathan Bahary, MD University of Pittsburgh
  More Information

No publications provided

Responsible Party: Nathan Bahary, MD, Associate Professor, Department of Medicine, Division of Oncology, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT00177307     History of Changes
Other Study ID Numbers: 04-118
Study First Received: September 12, 2005
Last Updated: December 18, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Pittsburgh:
colon
rectum

Additional relevant MeSH terms:
Colorectal Neoplasms
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Rectal Diseases
Bevacizumab
Capecitabine
Fluorouracil
Oxaliplatin
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014