Nelfinavir Mesylate in Treating Patients With Recurrent, Metastatic, or Unresectable Liposarcoma - Full Text View

Purpose

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	Intervention	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


Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase I/II Study of Nelfinavir in Liposarcoma

Resource links provided by NLM:

MedlinePlus related topics: Soft Tissue Sarcoma

Drug Information available for: Nelfinavir Nelfinavir Mesylate

Genetic and Rare Diseases Information Center resources: Liposarcoma Malignant Mesenchymal Tumor Soft Tissue Sarcoma

U.S. FDA Resources

Further study details as provided by City of Hope Medical Center:

Primary Outcome Measures:

Dose Limiting Toxicity (DLT) and Maximum Tolerated Dose (MTD) (Phase I) [ Time Frame: 4 weeks from start of treatment, up to 2 years ] [ Designated as safety issue: Yes ]
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. 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
Overall Response Rate (Phase II) [ Time Frame: After 3 cycles of treatment, up to 2 years. ] [ Designated as safety issue: No ]
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


Enrollment:	29
Study Start Date:	March 2006
Primary Completion Date:	July 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

Arms

Assigned Interventions

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

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.

Eligibility


Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00233948

Locations


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


Principal Investigator:	Warren Chow	Beckman Research Institute

More Information

No publications provided


Responsible Party:	City of Hope Medical Center
ClinicalTrials.gov Identifier:	NCT00233948 History of Changes
Other Study ID Numbers:	04090, NCI-2010-01263, CDR0000438712, FDA R01FD003006-03
Study First Received:	October 5, 2005
Results First Received:	February 2, 2015
Last Updated:	February 2, 2015
Health Authority:	United States: Food and Drug Administration United States: Institutional Review Board

Additional relevant MeSH terms:


Liposarcoma Sarcoma Neoplasms Neoplasms by Histologic Type Neoplasms, Adipose Tissue Neoplasms, Connective and Soft Tissue Nelfinavir Anti-HIV Agents Anti-Infective Agents	Anti-Retroviral Agents Antiviral Agents Enzyme Inhibitors HIV Protease Inhibitors Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Protease Inhibitors Therapeutic Uses

ClinicalTrials.gov processed this record on February 27, 2015