Bevacizumab and Capecitabine as First-Line Therapy in Treating Older Patients With Metastatic Colorectal Cancer

A Phase II Study of Capecitabine and Bevacizumab in Elderly Patients With Metastatic Colorectal Cancer

RATIONALE: 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. Drugs used in chemotherapy, such as capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bevacizumab together with capecitabine may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving bevacizumab together with capecitabine works as first-line therapy in treating older patients with metastatic colorectal cancer.

Study Overview

• Status: Terminated
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: capecitabine; Biological: bevacizumab

Detailed Description

OBJECTIVES:

Primary

• Determine the time to disease progression in older patients with metastatic colorectal cancer treated with bevacizumab and capecitabine as first-line therapy.

Secondary

• Determine the response rate in patients treated with this regimen.
• Determine the median survival of patients treated with this regimen.
• Determine the toxic effects of this regimen in these patients.

OUTLINE: This is an open-label study.

Patients receive bevacizumab IV over 30-90 minutes on day 1 and oral capecitabine twice daily on days 1-7. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study within 13-16 months.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • Buffalo, New York, United States, 14263-0001
      • Roswell Park Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 70 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically* or cytologically* confirmed colorectal cancer

  • Site of primary tumor must have been confirmed by endoscopy, radiography, or surgery
  • Metastatic disease NOTE: *Patients with a history of surgically treated colorectal cancer who subsequently develop recurrent metastatic disease do not require histologic or cytologic confirmation of metastatic disease unless an interval of > 5 years has elapsed between initial primary surgery and the development of metastases

• Measurable disease

  • At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan
• No known curative therapy exists
• No history or evidence of CNS disease by physical exam (e.g., primary brain tumor or brain or CNS metastases)

PATIENT CHARACTERISTICS:

Age

• 70 and over

Performance status

• ECOG 0-1

Life expectancy

• More than 3 months

Hematopoietic

• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Hemoglobin ≥ 9 g/dL
• No bleeding diathesis or coagulopathy

Hepatic

• Bilirubin normal
• AST and ALT ≤ 3 times upper limit of normal (ULN)
• INR < 1.5 (unless on therapeutic anticoagulants)
• No unstable or uncompensated hepatic disease

Renal

• Creatinine < 1.2 times ULN OR
• Creatinine clearance > 60 mL/min
• No unstable or uncompensated renal disease

Cardiovascular

• No history of stroke
• No uncontrolled hypertension (i.e., blood pressure > 150/100 mm Hg on medication)
• No myocardial infarction within the past year
• No New York Heart Association class II-IV congestive heart failure
• No unstable angina
• No serious cardiac dysrhythmia requiring medication
• No other clinically significant cardiovascular disease
• No other unstable or uncompensated cardiac disease

Pulmonary

• No unstable or uncompensated respiratory disease

Other

• Fertile patients must use effective contraception
• Able to receive oral medication
• No known hypersensitivity to fluorouracil or capecitabine
• No known dihydropyrimidine dehydrogenase deficiency
• No seizures not controlled by standard medical therapy
• No serious nonhealing wound, ulcer, or bone fracture
• No other malignancy within the past 5 years except completely excised nonmelanoma skin cancer (with no evidence of recurrent disease) or carcinoma in situ of the cervix
• No other severe or uncontrolled systemic disease

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No prior bevacizumab

Chemotherapy

• Prior adjuvant fluorouracil and leucovorin calcium allowed provided the last treatment was administered > 6 months before the development of metastatic disease
• No prior chemotherapy for metastatic colon cancer
• No prior irinotecan or oxaliplatin

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• See Disease Characteristics
• More than 28 days since prior and no concurrent major surgery
• More than 28 days since prior open biopsy
• More than 7 days since prior fine needle aspiration or core biopsy

Other

• More than 4 weeks since prior and no concurrent participation in another experimental drug study
• More than 30 days since prior non-approved or investigational drugs

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: Arm 1; Patients receive bevacizumab IV over 30-90 minutes on day 1 and oral capecitabine twice daily on days 1-7	Drug: capecitabine; Biological: bevacizumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Time to Progression	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response Rate	Overall Response (OR) = CR + PR.	1 year
Median Survival		1 year
Toxicity	Number of participants with an adverse event. Please refer to the adverse event reporting for more detail.	1 year

Collaborators and Investigators

• Sponsor: Roswell Park Cancer Institute
• Investigators: Principal Investigator: Marwan Fakih, MD, Roswell Park Cancer Institute

Study record dates

Study Major Dates

• Study Start: July 1, 2004
• Primary Completion (Actual): June 1, 2008

Study Registration Dates

• First Submitted: April 5, 2005
• First Submitted That Met QC Criteria: April 5, 2005
• First Posted (Estimate): April 6, 2005

Study Record Updates

• Last Update Posted (Estimate): July 4, 2014
• Last Update Submitted That Met QC Criteria: June 3, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Keywords: stage IV rectal cancer; stage IV colon cancer; recurrent colon cancer; recurrent rectal cancer
• 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; Bevacizumab
• Other Study ID Numbers: I 22204; RPCI-I-22204; GENENTECH-RPCI-I-22204