Sorafenib and Bevacizumab in Treating Patients With Metastatic Colorectal Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT00826540
First received: January 21, 2009
Last updated: January 14, 2014
Last verified: January 2014
  Purpose

This phase II trial is studying how well giving sorafenib together with bevacizumab works in treating patients with metastatic colorectal cancer. Sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. 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. Sorafenib and bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving sorafenib together with bevacizumab may kill more tumor cells


Condition Intervention Phase
Recurrent Colon Cancer
Recurrent Rectal Cancer
Stage IV Colon Cancer
Stage IV Rectal Cancer
Drug: sorafenib tosylate
Biological: bevacizumab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Sorafenib/Avastin® as Salvage Therapy in Patients With Metastatic Colorectal Cancer

Resource links provided by NLM:


Further study details as provided by Alliance for Clinical Trials in Oncology:

Primary Outcome Measures:
  • Progression-free Survival Rate [ Time Frame: At 3 months ] [ Designated as safety issue: No ]

    The primary endpoint of this trial is progression free survival at 3 months. All patients meeting the eligibility criteria who have signed a consent form and have begun treatment will be considered evaluable. Patients lost to follow-up before 3 months (e.g., progression, refusing further treatment, etc.) will be considered treatment failures. All eligible patients will be followed until death or a minimum of 3 years. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients.

    Progression is defined as at least a 20% increase in the sum of longest liameter of target lesions taking as reference the smallest sum longest diameter recorded since the treatment started or the appearance of one or more new lesions.



Secondary Outcome Measures:
  • Response Rate [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
    Simple frequency analysis will be conducted to see if response rate is related to prior treatment and the selected tumor biomarkers. Descriptive statistics will be used to investigate how prior treatment affects various other measures as well.

  • Overall Survival [ Time Frame: Time from registration to death, assessed up to 2 years ] [ Designated as safety issue: No ]
    The distribution of overall survival will be estimated using Kaplan-Meier methodology.

  • Feasibility of Study Treatment [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]

    Will be evaluated based on the number of patients who are able to

    > tolerate the regimen, how long they tolerate it and whether they elect to stop treatment.



Enrollment: 83
Study Start Date: September 2009
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (sorafenib tosylate and bevacizumab)
Patients receive sorafenib tosylate orally twice daily on days 1-5 and 8-12 and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Blood samples are collected at baseline and then periodically during study treatment for laboratory biomarker and pharmacogenetic studies
Drug: sorafenib tosylate
Given orally
Other Names:
  • BAY 43-9006
  • BAY 43-9006 Tosylate Salt
  • BAY 54-9085
  • Nexavar
  • SFN
Biological: bevacizumab
Given IV
Other Names:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • Avastin
  • rhuMAb VEGF

Detailed Description:

PRIMARY OBJECTIVES:

I. Evaluate proportion of patients who are progression-free at 3 months (in historic comparison with results for single-agent bevacizumab in ECOG 3200).

SECONDARY OBJECTIVES:

I. Response rate (RR) II. Overall survival (OS) III. Safety IV. Feasibility

OUTLINE: This is a multicenter study.

Patients receive sorafenib tosylate orally twice daily on days 1-5 and 8-12 and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. Blood samples are collected at baseline and then periodically during study treatment for laboratory biomarker and pharmacogenetic studies.

After completion of study treatment, patients are followed periodically for up to 2 years.

  Eligibility

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

Inclusion Criteria:

  • Diagnosis of stage IV colorectal cancer (histologic proof is not required)
  • Measurable disease

    • Spiral CT scan required for both pre- and post-treatment tumor assessments of lesions measuring 1-2 cm
  • Progressive disease during or within 6 months of most recent prior chemotherapy regimen (bevacizumab, fluoropyrimidine, oxaliplatin, or irinotecan-based treatment) OR considered ineligible for standard therapy
  • Documentation of submission of tumor material for Kirsten Rat Sarcoma (KRAS) testing available
  • Prior anti-epidermal growth factor receptor (EGFR) antibody therapy (e.g., cetuximab or panitumumab) required for patients with wild-type KRAS tumor
  • No known brain metastasis

    • Patients with neurological symptoms must undergo a CT scan or MRI of the brain to exclude brain metastasis
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Life expectancy ≥ 6 months
  • Hemoglobin ≥ 9.0 g/dL
  • Absolute neutrophil count (ANC) ≥ 1,500/mm³
  • Platelet count ≥ 100,000/mm³
  • White blood cell count (WBC) ≥ 3,400/mm³
  • International normalized ratio (INR) < 1.5 (≤ 3.0 if on anti-coagulation therapy [e.g., warfarin or heparin])
  • Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) ≤ 2.5 times ULN (≤ 5 times ULN if there is liver involvement)
  • Alkaline phosphatase ≤ 3 times ULN
  • Creatinine ≤ 1.5 times ULN
  • Urine protein:creatinine ratio < 1 OR urine dipstick < 2+ OR urine protein < 1,000 mg by 24-hour urine collection
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for ≥ 6 months after completion of study treatment (≥ 2 weeks after completion of treatment with sorafenib tosylate alone)
  • Willing to provide mandatory blood samples for translational research studies
  • Able to swallow whole pills
  • No inadequately controlled hypertension (i.e., systolic BP > 150 mm Hg or diastolic BP > 100 mm Hg on anti-hypertensive medications)
  • No prior hypertensive crisis or hypertensive encephalopathy
  • No myocardial infarction or unstable angina within the past 6 months
  • No congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias
  • No thrombolic or embolic events (e.g., cerebrovascular accident, including transient ischemic attacks) within the past 6 months
  • No hemorrhage or bleeding event > grade 3 within the past 4 weeks
  • No evidence or history of bleeding diathesis or coagulopathy (in the absence of therapeutic anticoagulation)
  • No greater than normal risk of bleeding
  • No active or recent hemoptysis (≥ ½ teaspoon of bright red blood per episode) within the past 30 days
  • No concurrent uncontrolled illness including, but not limited to, any of the following:

    • Ongoing or active infection
    • Symptomatic congestive heart failure
    • Unstable angina pectoris
    • Cardiac arrhythmia requiring anti-arrhythmic drugs
    • Psychiatric illness or social situations that would limit compliance with study requirements
  • No known HIV infection or chronic hepatitis B or C infection
  • No serious, non-healing wound, active ulcer, or untreated bone fracture

    • Patients with fractures secondary to metastatic disease are eligible after appropriate radiotherapy
  • No significant traumatic injury within the past 4 weeks
  • No known or suspected allergy or hypersensitivity to any component of bevacizumab, sorafenib tosylate, or their excipients or to any other agent given in the course of this study
  • No malabsorption problem
  • None of the following within the past 6 months:

    • Significant vascular disease (e.g., aortic aneurysm or aortic dissection)
    • Peripheral arterial thrombosis
    • Symptomatic peripheral vascular disease
    • Abdominal fistula
    • Gastrointestinal perforation
    • Intra-abdominal abscess
  • No other active malignancy within the past 3 years except non melanoma skin cancer or carcinoma in situ of the cervix

    • Prior malignancy allowed provided patient is not receiving other specific treatment for that malignancy (other than hormonal therapy)
  • No other concurrent investigational agent for this cancer
  • Prior radiotherapy allowed
  • No prior sorafenib tosylate
  • No prior discontinuation of bevacizumab due to adverse events
  • More than 4 weeks since prior and no concurrent participation in any other experimental drug study
  • More than 4 weeks since prior St. John's wort or rifampin
  • More than 4 weeks since prior and no concurrent major surgical procedure or open biopsy
  • More than 7 days since prior core biopsy or minor surgical procedure, including placement of a vascular access device
  • No concurrent anticoagulant, except low-dose warfarin or heparin for deep venous thrombosis prophylaxis
  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: NCT00826540

  Show 211 Study Locations
Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
Investigators
Principal Investigator: Axel Grothey North Central Cancer Treatment Group
  More Information

No publications provided

Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT00826540     History of Changes
Other Study ID Numbers: NCCTG-N054C, NCI-2009-01177, U10CA025224, CDR0000632342
Study First Received: January 21, 2009
Results First Received: November 27, 2013
Last Updated: January 14, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Colonic Neoplasms
Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Antibodies
Antibodies, Monoclonal
Bevacizumab
Sorafenib
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 23, 2014