- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00233948
Nelfinavir Mesylate in Treating Patients With Recurrent, Metastatic, or Unresectable Liposarcoma
A Phase I/II Study of Nelfinavir in Liposarcoma
RATIONALE: Antiviral drugs, such as nelfinavir mesylate, may help prevent cancer cells from spreading.
PURPOSE: This phase I/II trial is studying the side effects and best dose of nelfinavir mesylate and to see how well it works in treating patients with recurrent, metastatic, or unresectable liposarcoma.
Study Overview
Status
Conditions
Detailed Description
OBJECTIVES:
I. To assess the toxicity and tolerance of nelfinavir in patients with liposarcoma.
II. To define the maximum tolerated dose (MTD) of nelfinavir when given daily as a single agent and to describe the toxicities at each does studied.
III. To evaluate the pharmacokinetics of nelfinavir. IV. To assess the response rate and progression free survival in patients with liposarcoma treated with nelfinavir.
V. To evaluate the expression and activity of certain proteins in the tumors of patients entered on this study, which may be important to the cytotoxicity of nelfinavir (SREBP-1, p21, NFkB (NFkappaB), caspase 3).
OUTLINE: This is a phase I, dose-escalation study followed by a phase II study.
Patients receive oral nelfinavir mesylate twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
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California
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Duarte, California, United States, 91010
- City of Hope Medical Center
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Pasadena, California, United States, 91030
- South Pasadena Cancer Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion
- Patients must have histologically confirmed liposarcoma, which is recurrent, metastatic or unresectable
- There is no limit to prior chemotherapy regimens; in addition, patients may have prior radiation
- All patients must have measurable disease, defined as lesions that can be accurately measured in at least one dimension (>= 20 mm with conventional techniques or >= 10mm with spiral CT scan); pleural effusions and ascites will not be considered measurable, but may be present in addition to the measurable lesion(s)
- ECOG (Eastern Cooperative Oncology Group) performance status of 0, 1, or 2; patients should have an expected survival of at least 3 months
- Absolute neutrophil count >= 1,000/ul
- Platelets >= 75000/ul
- Total bilirubin =< 2.0 g/dl
- AST(SGOT)/ALT(SGPT) =< 2.0X institutional upper limit of normal
- Brain metastasis is not an exclusion; however, patients are only eligible if they have had successful control of the brain tumor(s) by surgery or radiation therapy
- All prior therapy must have been completed at least 3 weeks prior to the patient's entry on this trial
- No concurrent chemotherapy, radiotherapy, immunotherapy or other investigational agents
- Women of child-bearing potential and men must agree to use adequate contraception (barrier method of birth control) prior to study entry and for the duration of study participation; should a women become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- Ability to understand and willingness to sign a written informed consent document
Exclusion
- Patient has had prior treatment with or is currently taking a protease inhibitor
- Patients enrolled cannot be on the following medications: cisapride, triazolam, midazolam, ergot derivatives, amiodarone, quinidine, dihydropyridine calcium antagonists (amlodipine, felodipine, isradipine, nicardipine, nifedipine, nimodipine, and nisoldipine), sildenafil, dilantin, rifampin or oral contraceptives
- Uncontrolled intercurrent illness
- Patients must have recovered from any expected toxicities of previous chemotherapy or radiation therapy
Study Plan
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 |
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Experimental: Arm I
Patients receive oral nelfinavir mesylate twice daily on days 1-28.
Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
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Correlative studies
Correlative studies
Other Names:
Correlative studies
Other Names:
Correlative studies
Correlative studies
Other Names:
Correlative studies
Other Names:
Correlative studies
Other Names:
Given orally
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Dose Limiting Toxicity (DLT) (Phase I)
Time Frame: 4 weeks from start of treatment, up to 2 years
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DLT is defined as any grade III toxicity not reversible to grade II or less within one week, or any grade IV toxicity.
Hyperlipidemia, hyperglycemia, nausea, vomiting and diarrhea are not DLTs unless they are uncontrolled grade 3/4.
Dose delays lasting more than 2 weeks due to toxicity are considered a DLT.
Dose escalation schedule for nelfinavir: 1250 mg bid ; 1500 mg bid; 2125 mg bid; 3000 mg bid; 4250 mg bid ; 6000 mg bid ; 8500 mg bid ; 12000 mg bid
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4 weeks from start of treatment, up to 2 years
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Maximum Tolerated Dose (MTD) (Phase I)
Time Frame: 4 weeks from start of treatment, up to 2 years
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The highest dose tested in which fewer than 33% of patients experience an attributable DLT to the study drug, when at least 6 patients are treated at that dose and are evaluable for toxicity.
If PK analysis of 3 patients treated at 4250 mg bid and 3 patients at 3000 mg bid confirms that the first dose area under the curve and Cmax of nelfinavir does not increase appreciably at doses greater than 1875 mg BID then 3000 mg BID will be deemed the MTD.
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4 weeks from start of treatment, up to 2 years
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Overall Response Rate (Phase II)
Time Frame: After 3 cycles of treatment, up to 2 years.
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Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
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After 3 cycles of treatment, up to 2 years.
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Warren Chow, City of Hope Medical Center
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms, Connective and Soft Tissue
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms, Adipose Tissue
- Sarcoma
- Liposarcoma
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Enzyme Inhibitors
- Anti-HIV Agents
- Anti-Retroviral Agents
- Protease Inhibitors
- HIV Protease Inhibitors
- Viral Protease Inhibitors
- Nelfinavir
Other Study ID Numbers
- 04090
- NCI-2010-01263
- CDR0000438712 (Registry Identifier: PDQ)
- FDA R01FD003006-03 (Other Identifier: FDA Office of Orphan Products Development)
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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