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Efficacy Study of Sorafenib and Cyclophosphamide to Treat Neuroendocrine Tumors

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by:
University Health Network, Toronto
ClinicalTrials.gov Identifier:
NCT00605566
First received: January 18, 2008
Last updated: June 5, 2012
Last verified: June 2012
History of Changes
  Purpose

This is a phase II clinical trial to assess the efficacy of the combination of metronomic cyclophosphamide and tailored sorafenib dosing in advanced, progressive NET. NET are highly vascular tumors, and high VEGF expression has been correlated with worse clinical and pathological characteristics as well as poor prognosis. A novel antiangiogenic approach relies on targeting not only the endothelial cells but also rendering them more sensitive to VEGFR blockade by achieving pericyte detachment. In this study, the dose of sorafenib will be titrated up to a maximum of 800mg BID based on patients' toxicity and on a novel pharmacodynamic assay that measures inhibition of molecular target(PDGFR) in patients' peripheral blood mononuclear cells. Dual VEGFR targeting is achieved by administering sorafenib plus metronomic low dose cyclophosphamide.


Condition Intervention Phase
Neuroendocrine Tumors
 Drug: sorafenib and cyclophosphamide
 Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Supportive Care
Official Title: Tailored-dose Sorafenib Plus Metronomic Cyclophosphamide in Advanced Neuroendocrine Tumors (NET): a Phase II Clinical Trial Based on Individual Pharmacodynamic Assessment

Resource links provided by NLM:

MedlinePlus related topics: Cancer
U.S. FDA Resources

Further study details as provided by University Health Network, Toronto:

Primary Outcome Measures:
  • To determine the efficacy of combination sorafenib plus metronomic cyclophosphamide in advanced, progressive NET, as measured by the objective response rate (ORR), and to assess the feasibility of the individual dose adjustment of sorafenib. [ Time Frame: Every 8 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To assess the toxicity, time-to-progression (TTP), overall survival (OS), and 1 year survival rate. [ Time Frame: One year ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 41
Study Start Date: January 2008
Estimated Study Completion Date: May 2013
Primary Completion Date: March 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: I
Patients will receive sorafenib and cyclophosphamide.
 Drug: sorafenib and cyclophosphamide
During a run-in period, patient will start taking 50 mg QD of oral cyclophosphamide and 200 mg BID of sorafenib. On day 8 of run-in the patient will be evaluated for toxicity. In the absence of toxicity, the patient will be escalated to sorafenib 400 mg BID and continue on daily 50 mg of cyclophosphamide, or the patient will be informed to continue on sorafenib 200 mg BID and cyclophosphamide 50 mg QD. Dose escalation procedure will be repeated every 2 weeks until unable to tolerate the study drug, or a maximum of 800 mg BID is reached, or achievement of > 90% inhibition of phosphorylation of PDGFR/Raf axis in PBMC. After "run-in" period, patient begins cycle 1, each cycle will last 28 days. Both cyclophosphamide and sorafenib will be taken orally.
Other Names:
  • BAY 43-9006
  • Cytoxan

  Eligibility

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

Inclusion Criteria:

  • Histologically or cytologically confirmed neuroendocrine tumors
  • Progressive and measurable metastatic disease
  • Patients must not have disease that is currently amenable to surgery
  • Life expectancy of greater than 3 months
  • ECOG performance status ≤2
  • Patients must have normal organ and marrow function
  • Negative pregnancy test; agreement to use adequate birth control

Exclusion Criteria:

  • Patients receiving chemotherapy or radiotherapy within last 4 weeks
  • Patients that had received Sorafenib for advanced NET(neuroendocrine tumors) are not allowed
  • Any other investigational agents within 4 weeks of study
  • Patients with known brain metastases
  • History of allergic reactions to compounds of similar chemical/biologic composition to sorafenib or cyclophosphamide
  • Concurrent cancer from another primary site requiring treatment within the past 3 years
  • Uncontrolled intercurrent illness
  • Pregnant women and women who are breastfeeding
  • HIV-positive patients receiving combination anti-retroviral therapy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00605566

Locations
Canada, Ontario
Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Sponsors and Collaborators
University Health Network, Toronto
Investigators
Principal Investigator: Lillian Siu, MD University Health Network, Toronto
  More Information

No publications provided

Responsible Party: Dr. Lillian Siu, Drug Development Program, Princess Margaret Hospital
ClinicalTrials.gov Identifier: NCT00605566     History of Changes
Other Study ID Numbers: SOR-NET-001
Study First Received: January 18, 2008
Last Updated: June 5, 2012
Health Authority: Canada: Ethics Review Committee
Canada: Health Canada

Keywords provided by University Health Network, Toronto:
Neuroendocrine
sorafenib
cyclophosphamide
pharmacodynamic

Additional relevant MeSH terms:
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Cyclophosphamide
Sorafenib
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
 Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Protein Kinase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on May 16, 2013