Adult LiposarcomaPhase 1/2NCT00233948

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

A Phase 1/2 study testing nelfinavir mesylate, biopsy and laboratory biomarker analysis in people with Adult Liposarcoma and Recurrent Adult Soft Tissue Sarcoma, run by City of Hope Medical Center at 2 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Adult Liposarcoma, Recurrent Adult Soft Tissue Sarcoma, Stage III Adult Soft Tissue Sarcoma
What is being tested?: nelfinavir mesylate, biopsy and laboratory biomarker analysis
Type of treatment: Pill or oral medicine, Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 29 participants
Where: 2 sitesUnited States
Study dates: Mar 2006to Jul 2013
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Show all 13Show fewer

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

Who cannot join

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

Trial locations and contacts

2 sites in 1 country.

United States2 sites

City of Hope Medical Center
Duarte, California, 91010
South Pasadena Cancer Center
Pasadena, California, 91030

Other trials in United States

About this study

Official title: 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.

Read the detailed description

OBJECTIVES:

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.

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.

Conditions: Adult Liposarcoma, Recurrent Adult Soft Tissue Sarcoma, Stage III Adult Soft Tissue Sarcoma, Stage IV Adult Soft Tissue Sarcoma
Being tested: nelfinavir mesylate, biopsy, laboratory biomarker analysis, pharmacological study, gene expression analysis
Medical subject headings: Liposarcoma, Sarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

nelfinavir mesylateDrug
Also called Viracept
Given orally
biopsyProcedure or surgery
Also called biopsies
Correlative studies
laboratory biomarker analysisOther
Correlative studies
pharmacological studyOther
Also called pharmacological studies
Correlative studies
gene expression analysisGenetic
Correlative studies
western blottingGenetic
Also called Blotting, Western, Western Blot
Correlative studies
reverse transcriptase-polymerase chain reactionGenetic
Also called RT-PCR
Correlative studies
immunoenzyme techniqueOther
Also called immunoenzyme techniques
Correlative studies

Study groups in NCT00233948
Study group	Role	What they receive
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. Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: 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.
Measured: 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
Measured: After 3 cycles of treatment, up to 2 years.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Mar 2006Jul 2013

First posted6 Oct 2005 (estimated)
Study startMar 2006
Primary completionJul 2013

Why it stopped: Drug availability issues

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Adult LiposarcomaStudies of the same condition, open and under way.
More trials run by City of Hope Medical CenterThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 29 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00233948
Sponsor's protocol ID: 04090
Other IDs: NCI-2010-01263, CDR0000438712, FDA R01FD003006-03
Status last verified: Mar 2015
First submitted: 5 Oct 2005
Last updated: 1 Apr 2015
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Silmitasertib (CX-4945) in Combination With Chemotherapy for Relapsed Refractory Solid Tumors
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RecruitingObservational study
Precision Medicine Approaches for Neoadjuvant Therapy in High-risk Sarcoma Patients
Sarcoma, Sarcoma, Leiomyo-, Adult
RecruitingPhase 1
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Solid Tumor (Excluding CNS), Liver Cell Carcinoma
RecruitingPhase 2
Hypofractionated, 3-week, Preoperative Proton or X-ray Radiotherapy for Patients With Localized Soft Tissue Sarcoma
Soft Tissue Sarcoma (Excluding GIST), Soft Tissue Sarcoma Adult

All Adult Liposarcoma trials

Study at a glance

From the registry record, last updated by the sponsor on 1 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase I/II Study of Nelfinavir in Liposarcoma
ClinicalTrials.gov ID: NCT00233948
Acronym / sponsor ID: 04090
Conditions: Adult Liposarcoma, Recurrent Adult Soft Tissue Sarcoma, Stage III Adult Soft Tissue Sarcoma, Stage IV Adult Soft Tissue Sarcoma
Phase: Phase 1/2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Drug availability issues
Enrolment: 29 participants (actual)
Lead sponsor: City of Hope Medical CenterUniversity, hospital or other
Study start: Mar 2006
Primary completion: Jul 2013 (actual)
First posted: 6 Oct 2005 (estimated)
Results: Posted 23 Feb 2015

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

RATIONALE: Antiviral drugs, such as nelfinavir mesylate, may help prevent cancer cells from spreading.

Detailed description

OBJECTIVES:

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.

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

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Arm I	Experimental	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 techniquePatients receive oral nelfinavir mesylate twice daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (13 listed)

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

Key exclusion criteria (4 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
nelfinavir mesylateAlso: ViraceptGiven orally	Drug	Arm I
biopsyAlso: biopsiesCorrelative studies	Procedure or surgery	Arm I
laboratory biomarker analysisCorrelative studies	Other	Arm I
pharmacological studyAlso: pharmacological studiesCorrelative studies	Other	Arm I
gene expression analysisCorrelative studies	Genetic	Arm I
western blottingAlso: Blotting, Western, Western BlotCorrelative studies	Genetic	Arm I
reverse transcriptase-polymerase chain reactionAlso: RT-PCRCorrelative studies	Genetic	Arm I
immunoenzyme techniqueAlso: immunoenzyme techniquesCorrelative studies	Other	Arm I

Primary outcome

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
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.
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

Results and safety

Results posted to the registry on 23 Feb 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Phase I: Dose Level 1	4	3
Phase I: Dose Level II	3	3
Phase I: Dose Level III	3	3
Phase I: Dose Level IV	3	3
Phase I: Dose Level V	4	4
Phase II	12	12

Primary outcome: Dose Limiting Toxicity (DLT) (Phase I)

Time frame: 4 weeks from start of treatment, up to 2 years. Number. Unit: participants with DLTs

Measure	Phase I: Dose Level I n = 4	Phase I: Dose Level II n = 3	Phase I: Dose Level III n = 3	Phase I: Dose Level IV n = 3	Phase I: Dose Level V n = 4
Value	0	0	0	0	0

Population analysed: All patients receiving treatment were evaluated for DLT.

Primary outcome: Maximum Tolerated Dose (MTD) (Phase I)

Time frame: 4 weeks from start of treatment, up to 2 years. Number. Unit: mg

Measure	Phase I n = 17
Value	3000

Population analysed: All patients observed for 28 days while receiving a full course of therapy or who experienced a DLT. Patients withdrawing before completion of the first course, for reasons other than DLT, were replaced.

Primary outcome: Overall Response Rate (Phase II)

Time frame: After 3 cycles of treatment, up to 2 years.. Number. Unit: participants

Measure	Phase II n = 12
Value	1

Population analysed: Patients who complete 3 cycles of treatment or who terminate treatment for reasons of toxicity, or who progress prior to the completion of 3 cycles of therapy on the Phase II portion of the study.

Adverse events

Time frame: Adverse events were recorded over a period of 5 years, 2 months.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Phase I: Dose Level I	2 of 4 (50%)	4 of 4 (100%)	Not reported
Phase I: Dose Level II	0 of 3 (0%)	3 of 3 (100%)	Not reported
Phase I: Dose Level III	2 of 3 (66.7%)	3 of 3 (100%)	Not reported
Phase I: Dose Level IV	1 of 3 (33.3%)	3 of 3 (100%)	Not reported
Phase I: Dose Level V	0 of 4 (0%)	4 of 4 (100%)	Not reported
Phase II	2 of 12 (16.7%)	12 of 12 (100%)	Not reported

Limitations and caveats (from the sponsor): 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.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 1 Apr 2015.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Adult Liposarcoma

RecruitingPhase 2
A Study of Lifileucel (Tumor-infiltrating Lymphocytes) in Adults With Advanced Soft Tissue Sarcoma
Sarcoma, Soft Tissue Sarcoma (STS)
RecruitingPhase 1/2
Silmitasertib (CX-4945) in Combination With Chemotherapy for Relapsed Refractory Solid Tumors
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Precision Medicine Approaches for Neoadjuvant Therapy in High-risk Sarcoma Patients
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RecruitingPhase 2
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Warren Chow principal investigator

City of Hope Medical Center

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 1 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Feb 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose Limiting Toxicity (DLT) (Phase I) (time frame: 4 weeks from start of treatment, up to 2 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00233948.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Apr 2015.