- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00605566
Efficacy Study of Sorafenib and Cyclophosphamide to Treat Neuroendocrine Tumors
Tailored-dose Sorafenib Plus Metronomic Cyclophosphamide in Advanced Neuroendocrine Tumors (NET): a Phase II Clinical Trial Based on Individual Pharmacodynamic Assessment
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Ontario
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Toronto, Ontario, Canada, M5G 2M9
- Princess Margaret Hospital
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Supportive Care
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: I
Patients will receive 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:
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:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Efficacy of Combination Sorafenib Plus Metronomic Cyclophosphamide in Advanced, Progressive NET, as Measured by the Objective Response Rate (ORR).
Time Frame: Assessed from start of study treatment until death or disease progression, whichever occurs first up to 7 years
|
Objective response (complete and partial) evaluated using RECIST criteria. Complete response (CR): disappearance of all clinical and radiological evidence of tumour (both target and non-target). Partial response (PR): at least a 30% decrease in the sum of longest diameter of target lesions. |
Assessed from start of study treatment until death or disease progression, whichever occurs first up to 7 years
|
Association Between p-Shift Changes and Treatment Efficacy of Individual Dose Adjustment of Sorafenib
Time Frame: Assessed from start of study treatment until death, assessed up to 7 years.
|
A phosphoshift (pShift) flow cytometry-based test that measures RAF signal transduction capacity in peripheral blood cells was used in order to predict clinical course and/or guide individual dose-titration. Positive pShift values denote stimulation of RAF signal transduction, whereas negative pShift values denote inhibition of RAF signal transduction as measured by flow-cytometry. Associations between pShift changes and treatment efficacy were measured using progression-free survival (PFS) and overall survival (OS). |
Assessed from start of study treatment until death, assessed up to 7 years.
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Progression-free Survival (PFS)
Time Frame: Assessed from start of study treatment until death or disease progression, whichever occurs first up to 7 years
|
Progressive disease (PD): at least a 20% increase in the sum of the longest diameter of measured lesions.
|
Assessed from start of study treatment until death or disease progression, whichever occurs first up to 7 years
|
Overall Survival (OS)
Time Frame: Assessed from start of study treatment until death, assessed up to 7 years.
|
Assessed from start of study treatment until death, assessed up to 7 years.
|
|
1-year Survival Rate
Time Frame: 1 year
|
Survival rate at 1 year.
|
1 year
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Neuroendocrine Tumors
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antirheumatic Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Protein Kinase Inhibitors
- Cyclophosphamide
- Sorafenib
Other Study ID Numbers
- SOR-NET-001
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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