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

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

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

Study Overview

• Status: Completed
• Conditions: Cancer
• Intervention / Treatment: Drug: Bevacizumab; Drug: Capecitabine; Drug: Oxaliplatin

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.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	time from start of protocol therapy until objective tumor progression or death	Up to 27 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response Rate (RR)	Percentage of partial responses (PR) + complete responses (CR).	Up to 27 months
Overall Survival	time from start of protocol therapy until death from any cause	Up to 40 months
1-, 2-, and 3-year Overall Survival	Probability of being alive at 1-, 2-, and 3-years from start of protocol therapy	Up to 40 months

Collaborators and Investigators

• Sponsor: University of Pittsburgh
• Collaborators: Genentech, Inc.

Study record dates

Study Major Dates

• Study Start: January 1, 2005
• Primary Completion (ACTUAL): February 1, 2012
• Study Completion (ACTUAL): February 1, 2012

Study Registration Dates

• First Submitted: September 12, 2005
• First Submitted That Met QC Criteria: September 12, 2005
• First Posted (ESTIMATE): September 15, 2005

Study Record Updates

• Last Update Posted (ESTIMATE): July 12, 2016
• Last Update Submitted That Met QC Criteria: June 1, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Keywords: colon; rectum
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Capecitabine; Oxaliplatin; Bevacizumab
• Other Study ID Numbers: 04-118