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Nelfinavir Mesylate in Treating Patients With Recurrent, Metastatic, or Unresectable Liposarcoma

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ClinicalTrials.gov Identifier: NCT00233948
Recruitment Status : Terminated (Drug availability issues)
First Posted : October 6, 2005
Results First Posted : February 23, 2015
Last Update Posted : April 1, 2015
Sponsor:
Information provided by (Responsible Party):
City of Hope Medical Center

Study Description
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Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Adult Liposarcoma Recurrent Adult Soft Tissue Sarcoma Stage III Adult Soft Tissue Sarcoma Stage IV Adult Soft Tissue Sarcoma Drug: nelfinavir mesylate Procedure: biopsy Other: laboratory biomarker analysis Other: pharmacological study Genetic: gene expression analysis Genetic: western blotting Genetic: reverse transcriptase-polymerase chain reaction Other: immunoenzyme technique Phase 1 Phase 2

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 29 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Study of Nelfinavir in Liposarcoma
Study Start Date : March 2006
Actual Primary Completion Date : July 2013

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
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.
 Drug: nelfinavir mesylate
Given orally
Other Name: Viracept

Procedure: biopsy
Correlative studies
Other Name: biopsies

Other: laboratory biomarker analysis
Correlative studies

Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Genetic: gene expression analysis
Correlative studies

Genetic: western blotting
Correlative studies
Other Names:
  • Blotting, Western
  • Western Blot

Genetic: reverse transcriptase-polymerase chain reaction
Correlative studies
Other Name: RT-PCR

Other: immunoenzyme technique
Correlative studies
Other Name: immunoenzyme techniques


Outcome Measures
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Primary Outcome Measures :
  1. Dose Limiting Toxicity (DLT) (Phase I) [ Time Frame: 4 weeks from start of treatment, up to 2 years ]
    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

  2. Maximum Tolerated Dose (MTD) (Phase I) [ Time Frame: 4 weeks from start of treatment, up to 2 years ]
    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.

  3. Overall Response Rate (Phase II) [ Time Frame: After 3 cycles of treatment, up to 2 years. ]
    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


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00233948


Locations
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United States, California
City of Hope Medical Center
Duarte, California, United States, 91010
South Pasadena Cancer Center
Pasadena, California, United States, 91030
Sponsors and Collaborators
City of Hope Medical Center
Investigators
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Principal Investigator: Warren Chow City of Hope Medical Center
More Information
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Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT00233948    
Other Study ID Numbers: 04090
NCI-2010-01263
CDR0000438712 ( Registry Identifier: PDQ )
FDA R01FD003006-03 ( Other Identifier: FDA Office of Orphan Products Development )
First Posted: October 6, 2005    Key Record Dates
Results First Posted: February 23, 2015
Last Update Posted: April 1, 2015
Last Verified: March 2015
Additional relevant MeSH terms:
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Sarcoma
Liposarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Adipose Tissue
Nelfinavir
HIV Protease Inhibitors
 Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents