Combination Chemotherapy and Bevacizumab in Treating Patients With Stage IV Colorectal Cancer

Phase II Study of Avastin, Irinotecan, High Dose 24 Hour Continuous Intravenous Infusion of Floxuridine and Leucovorin in Patients With Previously Untreated Metastatic Colorectal Cancer

RATIONALE: Drugs used in chemotherapy, such as irinotecan, floxuridine, and leucovorin, 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. Bevacizumab may also stop the growth of colorectal cancer by blocking blood flow to the tumor. Giving combination chemotherapy together with bevacizumab may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving combination chemotherapy together with bevacizumab works in treating patients with stage IV colorectal cancer.

Study Overview

• Status: Terminated
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: Leucovorin; Drug: Irinotecan; Biological: Bevacizumab; Drug: Floxuridine

Detailed Description

For the purpose of this study treatment cycle consist of six weeks, 2 weeks of consecutive treatment followed by 1 week of rest and 2 weeks of treatment followed by one week of rest. Treatment will be administered weekly, 4 out 6 weeks, on days 1, 8, 22 and 29 according to the schedule. There will be no treatment delivered on weeks 3 & 6 (Days 15 and 36).

Disease will be evaluated by CT scan at the completion of every two cycles. Patients with complete response (CR), or partial response (PR), will be evaluated for possible surgical resection. Patients who become operable will continue to be evaluated for survival and disease relapse. Patients with stable disease (SD), and those with less than pCR after surgery should continue chemotherapy until radiographic evidence of tumor progression is identified or unacceptable side effects.

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients must have stage IV, histologically confirmed diagnosis of Adenocarcinoma of the colon.
2. Patients must have bi-dimensionally measurable disease since the purpose of this study is to determine efficacy of treatment.
3. Patients must be previously untreated.
4. Patients must be over the age of 18 years.
5. Patients may not be pregnant. Patients of childbearing years must be using contraception.
6. Patients must have ECOG performance status of 0-1 or KPS of at least 70.
7. Patients must have life expectancy of ≥ two months.
8. Patients must have a white blood cell count of ≥1000/mm³ ANC > 1.0, platelets > 100,000/mm³.
9. Patients must have adequate renal function as documented by a serum creatinine of ≤ 1.5 mg/dl.
10. Patients must have a bilirubin of ≤ 1.5 mg/dl and an SGOT of ≤ three times normal for patients with no liver disease, and ≤ five times normal for those with liver metastases.
11. Patients must be informed of the investigational nature of the study and give written informed consent.
12. Patients must have indwelling central venous catheter or good peripheral intravenous catheter, preferably a port-a-cath.
13. Patients may have had prior surgery for their colorectal cancer. Patients must be at least 8 weeks beyond surgery and recovered from all effects of surgery.
14. Patients enrolled in this study may have a history of prior malignancy (5 years ago) provided that the patient is currently disease-free.

Exclusion Criteria:

1. Patients who have had prior chemotherapy or radiation therapy for their colorectal cancer, with exception of adjuvant chemo/radiation therapy.
2. Patients receiving concomitant radiation, hormonal therapy, chemotherapy, or immunotherapy.
3. Patients receiving any investigational drug within 30 days prior to start of this study.
4. Patients with serious underlying medical illnesses (including Congestive Heart Failure New York Heart Association Functional Classification 2-4) or active infection.
5. Patients with central nervous system metastasis must have completed radiation prior to entry into this protocol.
6. Patients with psychiatric conditions or associated conditions which would make participating in this study dangerous to their health.
7. Patients with uncontrolled hypertension.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Combination Chemotherapy and Bevacizumab; Treatment cycle is 6 weeks, 2 weeks of consecutive treatment followed by 1 week of rest and 2 weeks of treatment followed by one week of rest. Treatment will be administered weekly, 4 out 6 weeks, on days 1, 8, 22 and 29: Bevacizumab: 7.5mg/kg via intravenous (IV) infusion on Days 1 and 22;; Irinotecan: 110 mg/m^2 via IV infusion on Days 1, 8, 22, 29;; Leucovorin: 500 mg/m^2 via IV infusion on Days 1, 8, 22 and 29;; Floxuridine: 120 mg/kg over continuous infusion on Days 1, 8, 22 and 29.

Drug: Leucovorin; Other Names: Leucovorin calcium; Drug: Irinotecan; Other Names: Camptosar; Irinotecan Hydrochloride; Biological: Bevacizumab; Other Names: Avastin; Drug: Floxuridine; Other Names: 5-fluorodeoxyuridine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival up to 2 Years	Percentage of patients with overall survival times of up to 2 years	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response Rate (Complete Response and Partial Response)	Percentage of patients achieving complete response or partial response per RECIST criteria ver 1.0	2 years
Median Progression-free Survival in Months	Median number of months subjects achieved progression-free survival	2 years
Rate of Toxicity in Study Participants	Evaluation the safety and toxicities of protocol regimen as evidenced by the rate of serious adverse events in study participants.	2 years

Collaborators and Investigators

• Sponsor: University of Miami
• Investigators: Principal Investigator: Bach Ardalan, MD, University of Miami

Publications and helpful links

General Publications

• Phase II study of bevacizumab (B), camptosar (I), high-dose 24-hour continuous intravenous infusion of floxuridine (F) and leucovorin (L) in patients with previously untreated metastatic colon cancer. (B-IFL) B. Ardalan, M. Feagans, D. Mezentsev, C. Jones, P. R. Subbarayan, G. Walker, M. Sapp, K. Stephenson, J. Ness, D. Franceschi, and A. Livingstone Journal of Clinical Oncology 2009 27:15S, e15114-e15114

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2006
• Primary Completion (Actual): March 1, 2010
• Study Completion (Actual): March 1, 2010

Study Registration Dates

• First Submitted: March 15, 2007
• First Submitted That Met QC Criteria: March 15, 2007
• First Posted (Estimate): March 19, 2007

Study Record Updates

• Last Update Posted (Actual): May 11, 2017
• Last Update Submitted That Met QC Criteria: April 5, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: adenocarcinoma of the rectum; stage IV rectal cancer; stage IV colon cancer; adenocarcinoma of the colon
• 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; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Protective Agents; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Micronutrients; Vitamins; Topoisomerase I Inhibitors; Antidotes; Vitamin B Complex; Bevacizumab; Leucovorin; Irinotecan; Levoleucovorin; Floxuridine
• Other Study ID Numbers: 20060042; SCCC-2005145 (Other Identifier: University of Miami Sylvester Comprehensive Cancer Center); WIRB-20060252 (Other Identifier: Western Institutional Review Board)