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

NCT00233948 | Terminated Phase 1 Results DMC

• 4 other identifiers: 04090NCI-2010-01263CDR0000438712FDA R01FD003006-03
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 2

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.

Conditions

Adult Liposarcoma; Recurrent Adult Soft Tissue Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage IV Adult Soft Tissue Sarcoma

Outcome Measures

Primary Outcomes (3)

• Dose Limiting Toxicity (DLT) (Phase I)

  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

  4 weeks from start of treatment, up to 2 years

• Maximum Tolerated Dose (MTD) (Phase I)

  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.

  4 weeks from start of treatment, up to 2 years

• Overall Response Rate (Phase II)

  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

  After 3 cycles of treatment, up to 2 years.

Study Arms (1)

Arm I

EXPERIMENTAL

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; 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

Interventions

nelfinavir mesylate DRUG

Given orally

Also known as: Viracept

Arm I

biopsy PROCEDURE

Correlative studies

Also known as: biopsies

Arm I

laboratory biomarker analysis OTHER

Correlative studies

Arm I

pharmacological study OTHER

Correlative studies

Also known as: pharmacological studies

Arm I

gene expression analysis GENETIC

Correlative studies

Arm I

western blotting GENETIC

Correlative studies

Also known as: Blotting, Western, Western Blot

Arm I

reverse transcriptase-polymerase chain reaction GENETIC

Correlative studies

Also known as: RT-PCR

Arm I

immunoenzyme technique OTHER

Correlative studies

Also known as: immunoenzyme techniques

Arm I

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• City of Hope Medical Center: lead

Study Sites (2)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

South Pasadena Cancer Center

Pasadena, California, 91030, United States

Location

MeSH Terms

Conditions

Liposarcoma; Sarcoma

Interventions

Nelfinavir; Biopsy; Gene Expression Profiling; Blotting, Western; Reverse Transcriptase Polymerase Chain Reaction; Immunoenzyme Techniques

Condition Hierarchy (Ancestors)

Neoplasms, Adipose Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Genetic Techniques; Electrophoresis; Chemistry Techniques, Analytical; Electrochemical Techniques; Immunoblotting; Immunoassay; Immunologic Techniques; Molecular Probe Techniques; Polymerase Chain Reaction; Nucleic Acid Amplification Techniques; Immunohistochemistry

Limitations and Caveats

After 12 patients were accrued to the Phase II portion, the study was terminated…protocol objectives for the Phase II portion not met. Closed prematurely due to drug availability issues.

Results Point of Contact

• Title: Paul Frankel, Ph.D.
• Organization: City of Hope

pfrankel@coh.org

626-256-4673

Study Officials

• Warren Chow

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 5, 2005
• First Posted: October 6, 2005
• Study Start: March 1, 2006
• Primary Completion: July 1, 2013
• Last Updated: April 1, 2015
• Results First Posted: February 23, 2015

Record last verified: 2015-03

Locations

US (2)