A Trial of the Protease Inhibitor Nelfinavir and Concurrent Radiation and Temozolomide in Patients With WHO Grade IV Glioma

NCT01020292 | Completed Phase 1 DMC

• 1 other identifier: UPCC 01309
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial will determine safety, dose-limiting toxicities (DLT) and maximum tolerable dose (MTD) of the protease inhibitor, Nelfinavir (NFV), when given with chemoradiotherapy as post-operative therapy for glioblastoma multiforme (GBM). Oral NFV is a standard therapy for patients with HIV and the safety of 1250 mg BID NFV is well-established. Case studies have also reported that HIV patients have received radiotherapy for cancer, while on 1250 mg BID NFV. This is the first trial of oral NFV and chemoradiotherapy for GBM patients. Although unacceptable toxicity is unlikely, two NFV dose levels (625, and 1250 mg BID) will be evaluated in a cohort escalation design of 3-6 subjects. At the MTD, 19 additional subjects will be enrolled to generate pilot data on radiographic response and to evaluate further toxicity. A maximum of 31 subjects will be enrolled on the trial.

Conditions

Glioma

Keywords

Adult subjects with a diagnosis of Grade IV Glioma

Outcome Measures

Primary Outcomes (1)

• To determine the safety, dose-limiting toxicities, and maximally tolerated dose of NFV concurrently with radiation and temozolomide.

  One year

Secondary Outcomes (1)

• To determine the progression free survival (PFS) and overall survival (OS) with an exploratory analysis to compare the observed median value obtained in this study to the historical median values of 6.9 months and 14.6 months respectively.

  Two years

Study Arms (1)

NFV and Concurrent ChemoRads

EXPERIMENTAL

Drug: Nelfinavir

Interventions

Nelfinavir DRUG

NFV and Concurrent ChemoRads

Eligibility Criteria

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

You may qualify if:

• Patients \> 18 years old.
• Newly diagnosed and histologically confirmed supratentorial WHO Grade IV astrocytoma status-post maximally achievable resection.
• ECOG performance status 0-2.
• Absolute Neutrophil Count ≥ 1500 per mm3
• Platelet count ≥ 100,000 per mm3
• Serum creatinine \< 1.5 times the upper limit of normal
• Serum AST or ALT \< 2 times the upper limit of normal
• Serum bilirubin \< 1.5 mg/dl
• Patients who were receiving corticosteroids have to receive a stable or decreasing dose for at least 14 days before randomization.
• No prior cranial radiotherapy will be permitted.
• No known HIV infection.
• The effects of NFV on the developing human fetus have been studied in HIV positive women.
• We do not, however, know the risks along with radiation. Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• Patients must sign an informed consent document that indicates they are aware of the investigative nature of the treatment in this protocol as well as the potential risks and benefits.

You may not qualify if:

• Prior cranial radiotherapy.
• Patients may not be receiving or have received any other investigational agents during/or within 1 month prior to treatment with NFV.
• Pregnant or lactating women.
• Patients receiving the following drugs that are contraindicated with NFV will be excluded: antiarrhythmics (amiodarone, quinidine), antimycobacterial (rifampin), ergot derivatives (dihydroergotamine, ergonovine, ergotamine, methylergonovine), herbal products (St. John's wort), HMG-CoA reductase inhibitors (lovastatin, simvastatin), neuroleptic (pimozide), proton pump inhibitors, sedatives/hypnotics (midazolam, triazolam).
• Patients receiving the following drugs will be clinically evaluated as to whether dosage/medication can be changed to permit patient on study: anti-convulsants (carbamazepine, phenobarbital, phenytoin), anti-mycobacterial (rifabutin), PDE5 inhibitors (sildenafil, vardenafil, tadalafil), HMG-CoA reductase inhibitor (atorvastatin, rosuvastatin), immunosuppressants (cyclosporine, tacrolimus, sirolimus), narcotic analgesic (methadone), oral contraceptive (ethinyl estradiol), macrolide antibiotic (azithromycin), antidepressant (trazadone).

Sponsors & Collaborators

• Abramson Cancer Center at Penn Medicine: lead

Study Sites (1)

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Glioma

Interventions

Nelfinavir

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

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

Study Record Dates

• First Submitted: November 23, 2009
• First Posted: November 24, 2009
• Study Start: April 1, 2009
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2017
• Last Updated: April 12, 2019

Record last verified: 2019-04

Locations

US (1)