Phase II Trial of Nelfinavir With Concurrent Chemoradiotherapy in Squamous Cell Carcinoma of the Head and Neck

NCT02207439 | Completed Phase 2 Results DMC

• 1 other identifier: UPCC 15313
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase II trial of definitive chemoradiotherapy (CTRT) given with the protease inhibitor,Nelfinavir (NFV), in patients with locally advanced head and neck. Eligible patients will receive a "lead-in" period of Nelfinavir (1250 mg po bid) for 7-14 days prior to initiation of CTRT. Nelfinavir will then be given concurrently with platinum-based chemotherapy and radiation therapy (planned total dose of 70 Gy over 7 weeks).

Conditions

Head and Neck Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Locoregional Control

  locoregional control determined via diagnostic imaging and clinical examination.

  5 years

Secondary Outcomes (2)

• Decrease in Hypoxia From Nelfinavir

  7-14 days

• Change in Glucose Metabolism From Nelfinavir

  From the initiation of any study procedures to 30 days following the completion of 7 chemoradiation

Study Arms (1)

Single Arm Phase 2

EXPERIMENTAL

Single Arm, Phase II study of Nelfinavir Lead-In (Period 1) Followed by Concurrent Chemoradiation with Nelfinavir (Period 2)

Drug: Nelfinavir (Viracept®) 1250 mg; Other: Chemoradiation

Interventions

Nelfinavir (Viracept®) 1250 mg DRUG

Period 1: Nelfinavir Lead-In (1250 mg bid, 7-14 days).

Also known as: Nelfinavir Lead-In

Single Arm Phase 2

Chemoradiation OTHER

Period 2: Concurrent Chemoradiation (70 Gy over 7 weeks) with Nelfinavir (1250 mg bid)

Single Arm Phase 2

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.
• Histologically confirmed diagnosis of squamous cell carcinoma of the oral cavity, oropharynx, larynx, or hypopharynx stages III, IVa, or IVb, p16-negative on immunohistochemistry
• Determined by the treating physician to be a candidate for organ preserving, concurrent standard chemotherapy and radiation therapy to the head and neck with definitive intent.
• ECOG Performance Status 0-2
• Patients must sign an informed consent document that indicates they are aware of the investigational nature of the treatment in this protocol as well as the potential risks and benefits.
• The effects of EF5 on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry, during study, until 1 month after completion of the final FMISO PET/CT scan. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. Serum pregnancy testing will be required for women of childbearing potential.
• Ability to understand and the willingness to sign a written informed consent.

You may not qualify if:

• Prior radiation therapy to the head and neck
• Prior chemotherapy within the past 5 years
• Previous therapy with a human immunodeficiency virus (HIV) protease inhibitor
• Pregnant or lactating patients.
• Patients with known HIV disease. These patients have a high probability of treatment with anti-retroviral therapy which may interact with the nelfinavir.
• 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 \> 1.2 mg/dl
• Weight loss of \> 10% over the past 6 months which is due to tumor wasting syndrome
• Distant metastases
• 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 (hypericum perforatum), HMG-CoA Reductase Inhibitors: lovastatin,simvastatin, Neuroleptic:pimozide, Proton Pump Inhibitors, Sedative/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, Anti-Convulsant:phenytoin, Anti-Mycobacterial:rifabutin, PDE5 Inhibitors: sildenafil, vardenafil, tadalafil, HMG-CoA: Reductase Inhibitors: atorvastatin, rosuvastatin, Immuno-suppressants: cyclosporine,tacrolimus, sirolimus, Narcotic Analgesic: methadone, Oral Contraceptive:ethinyl estradiol, Macrolide Antibiotic:azithromycin, Inhaled/nasal steroid fluticasone, Antidepressant: trazodone.
• Women of childbearing potential who have a positive result on screening urine pregnancy test.

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

Squamous Cell Carcinoma of Head and Neck

Interventions

Nelfinavir; Chemoradiotherapy

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Combined Modality Therapy; Therapeutics; Drug Therapy; Radiotherapy

Results Point of Contact

• Title: Alexander Lin, MD
• Organization: University of Pennsylvania

alexander.lin2@pennmedicine.upenn.edu

215-662-3198

Study Officials

• Alexander Lin, MD

  Abramson Cancer Center at Penn Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 31, 2014
• First Posted: August 4, 2014
• Study Start: July 1, 2014
• Primary Completion: May 1, 2021
• Study Completion: May 1, 2022
• Last Updated: July 25, 2023
• Results First Posted: July 25, 2023

Record last verified: 2023-06

Locations

US (1)