Efficacy Study of Sorafenib and Cyclophosphamide to Treat Neuroendocrine Tumors - Full Text View

Sponsor:	University Health Network, Toronto
Information provided by:	University Health Network, Toronto
ClinicalTrials.gov Identifier:	NCT00605566

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 II

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

Drug Information available for: Cyclophosphamide Sorafenib Sorafenib tosylate

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 Primary Completion Date:	December 2010 (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

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:	October 27, 2010
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 February 12, 2012