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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier:
NCT00665990
First received: April 22, 2008
Last updated: September 8, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
Refractory Solid Tumors
Leukemia
Drug: Bevacizumab
Drug: Sorafenib
Drug: Cyclophosphamide
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of Bevacizumab and Sorafenib Combined With Low Dose Cyclophosphamide in Patients With Refractory Solid Tumors and Leukemia

Resource links provided by NLM:


Further study details as provided by St. Jude Children's Research Hospital:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: Yes ]

Enrollment: 49
Study Start Date: November 2007
Study Completion Date: August 2013
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Cytoxan(R)

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.

  Eligibility

Ages Eligible for Study:   up to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  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: NCT00665990

Locations
United States, Tennessee
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105
Sponsors and Collaborators
St. Jude Children's Research Hospital
Investigators
Principal Investigator: Fariba Navid, MD St. Jude Children' Research Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT00665990     History of Changes
Other Study ID Numbers: ANGIO1
Study First Received: April 22, 2008
Last Updated: September 8, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia
Neoplasms
Neoplasms by Histologic Type
Bevacizumab
Cyclophosphamide
Sorafenib
Alkylating Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Enzyme Inhibitors
Growth Inhibitors
Growth Substances
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014