Phase I Study of Bevacizumab and Sorafenib Combined With Low Dose Cyclophosphamide in Patients With Refractory Solid Tumors and Leukemia

January 8, 2015 updated by: St. Jude Children's Research Hospital
Phase I Study of Bevacizumab and Sorafenib Combined with Low Dose Cyclophosphamide in Patients with Refractory Solid Tumors and Leukemia. Patients with solid tumors (including central nervous tumors) that are recurrent or refractory to standard therapy, or for whom standard therapy is not available. Once a maximum tolerated dose (MTD) has been established in patients with recurrent or refractory solid tumors, the tolerability of this dose will be tested in patients with refractory or recurrent leukemia and an expanded cohort of patients with refractory or recurrent solid tumors.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Phase I Study of Bevacizumab and Sorafenib Combined with Low Dose Cyclophosphamide in Patients with Refractory Solid Tumors and Leukemia. Patients with solid tumors (including central nervous tumors) that are recurrent or refractory to standard therapy, or for whom standard therapy is not available. Once a maximum tolerated dose (MTD) has been established in patients with recurrent or refractory solid tumors, the tolerability of this dose will be tested in a maximum of 6 patients, in cohorts of 3, with refractory or recurrent leukemia and a maximum of 24 evaluable patients, in cohorts of 6, with refractory or recurrent solid tumors.

Approximately 21-24 patients with refractory solid tumors to define the maximum tolerated dose (MTD) and 6 patients with recurrent or refractory leukemia,12 patients with refractory or recurrent bone or soft tissue sarcomas and 12 patients with other refractory or recurrent solid tumors (including lymphomas) to test the tolerability of this MTD in patients with hematological malignancies. Bevacizumab will be administered intravenously at a starting dose of 5 mg/kg every 3 weeks with sorafenib by mouth every 12 hrs at a starting dose of 90 mg/m2 every 12 hours and cyclophosphamide by mouth daily at a dose of 50 mg/m2/day (dose level 1). A course of therapy will be considered to be of 21 days duration. Once a maximum tolerated dose of sorafenib (sMTD) in combination with bevacizumab and cyclophosphamide has been determined, 6 patients with recurrent or refractory leukemia will be then be evaluated at the solid tumor MTD to test the tolerability of this combination in patients with hematological malignancies.

Study Type

Interventional

Enrollment (Actual)

49

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Tennessee
      • Memphis, Tennessee, United States, 38105
        • St. Jude Children's Research Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

NOTE: As of May 2013, enrollment of solid tumor participants was completed. Participants with a diagnosis of leukemia continue to be enrolled.

  • Diagnosis: Solid tumors, including central nervous system tumors and lymphomas, that are recurrent or refractory to standard therapy or for which there is no standard therapy. Histologic verification of diagnosis is required.
  • Age: < or = 21 years of age at the time of original diagnosis
  • Life expectancy: at least 8 weeks
  • Performance status: Karnofsky > or = 50 for > 10 years of age; Lansky > or = 50 for children < or = 10 years of age.
  • Organ Function: Must have adequate organ and marrow function
  • Prior Therapy: Patient must have fully recovered from the acute toxic effects of all prior therapy prior to enrolling on study.
  • Must not have current or recent use of full-dose anticoagulants
  • Must not have received medications known to inhibit platelet function or known to selectively inhibit cyclooxygenase-2 (COX-2) activity
  • Bevacizumab and sorafenib should not be administered to pregnant women.
  • Pregnancy tests must be obtained in girls who are > 10 years of age or post-menarchal.
  • Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.
  • Breast feeding should be discontinued if a mother wishes to participate in this study.
  • Patients with a documented, chronic non-healing wound, ulcer, or bone fracture or history of a major surgical procedure or significant traumatic injury within 28 days prior to beginning therapy should be excluded due to preclinical evidence supporting the potential for delayed wound healing.
  • Patients must not have a deep venous or arterial thrombosis (including pulmonary embolism) within the last three months prior to study entry, and must not have a known thrombophilic condition
  • Patients must not have a history of myocardial infarction, severe or unstable angina, or severe peripheral vascular disease.
  • Ability to understand and willingness of research participant or legal guardian/representative to give written informed consent.

Exclusion Criteria:

  • Body surface area < 0.3 m2
  • Presence of a known bleeding diathesis or coagulopathy
  • Patients with evidence of intra-tumoral central nervous system hemorrhage. in current scans. Patients are required to have a head CT or MRI within 2 weeks prior to study enrollment.
  • Patients with known hypersensitivity to other recombinant human antibodies
  • Patients who have an uncontrolled infection
  • Patients with recurrent or refractory leukemia will be excluded from the dose escalation component of the phase I trial.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: Treatment
All participants will receive bevacizumab, sorafenib, and cyclophosphamide until maximum tolerated dose is reached.
Drug: Bevacizumab
Bevacizumab starting dose of 5 mg/kg every 3 weeks increasing in combination with Sorafenib and Cyclophosphamide until maximum tolerated dose
Other Names:
  • rhuMab VEGF
  • Avastin(R)
Drug: Sorafenib
Sorafenib 90 mg/m2 PO every 12 hours increasing in combination with Bevacizumab and Cyclophosphamide until maximum tolerated dose
Other Names:
  • BAY-43-9006
  • Nexavar(R)
Drug: Cyclophosphamide
Cyclophosphamide 50 mg/m2 PO once daily increasing in combination with Bevacizumab and Sorafenib until maximum tolerated dose
Other Names:
  • Cytoxan(R)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Determine the maximum tolerated dose and dose limiting toxicity of bevacizumab and sorafenib administered in combination with low dose cyclophosphamide to patients with refractory solid tumors.
Time Frame: 3 years
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

St. Jude Children's Research Hospital

Investigators

  • Principal Investigator: Sara Federico, MD, St. Jude Children' Research Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2007

Primary Completion (Actual)

August 1, 2013

Study Completion (Actual)

August 1, 2013

Study Registration Dates

First Submitted

April 22, 2008

First Submitted That Met QC Criteria

April 23, 2008

First Posted (Estimate)

April 24, 2008

Study Record Updates

Last Update Posted (Estimate)

January 9, 2015

Last Update Submitted That Met QC Criteria

January 8, 2015

Last Verified

January 1, 2015

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ANGIO1
  • NCI-2011-01146 (Registry Identifier: NCI Clinical Trial Registration Program)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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