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

Phase 1

Terminated

Conditions: Stage III Adult Soft Tissue Sarcoma
Adult Liposarcoma
Recurrent Adult Soft Tissue Sarcoma
Stage IV Adult Soft Tissue Sarcoma

Interventions: 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

Registration Number: NCT00233948

Lead Sponsor: City of Hope Medical Center

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.

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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 29

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm I	biopsy	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.
Arm I	gene expression analysis	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.
Arm I	reverse transcriptase-polymerase chain reaction	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.
Arm I	immunoenzyme technique	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.
Arm I	laboratory biomarker analysis	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.
Arm I	nelfinavir mesylate	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.
Arm I	pharmacological 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.
Arm I	western blotting	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.

Primary Outcome Measures

Name	Time	Method
Dose Limiting Toxicity (DLT) (Phase I)	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
Maximum Tolerated Dose (MTD) (Phase I)	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.
Overall Response Rate (Phase II)	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

Secondary Outcome Measures

Name	Time	Method

Trial Locations

Locations (2): City of Hope Medical Center
🇺🇸
Duarte, California, United States
South Pasadena Cancer Center
🇺🇸
Pasadena, California, United States