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

A Phase II Trial of a Protease Inhibitor, Nelfinavir (NFV), Given With Definitive, Concurrent Chemoradiotherapy (CTRT) in Patients With Locally-Advanced, Human Papilloma Virus (HPV) Negative, Squamous Cell Carcinoma of the Head and Neck

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).

Study Overview

• Status: Completed
• Conditions: Head and Neck Squamous Cell Carcinoma
• Intervention / Treatment: Drug: Nelfinavir (Viracept®) 1250 mg; Other: Chemoradiation

Detailed Description

This is a single-arm Phase II study of organ-preservation chemoradiotherapy given in combination with the protease inhibitor, Nelfinavir, in patients with stage II, IVa, or IVb (per AJCC version 7) squamous cell carcinoma of the oral cavity, oropharynx, larynx, or hypopharynx. Patients start treatment with Nelfinvir at a dose of 1250 mg twice daily for 7-14 days, before continuing Nelfinvir at this dose concurrent with chemotherapy and radiation therapy (for a total dose of 70 Gy over a period of 7 weeks).

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Abramson Cancer Center of the University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria

• 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.
• Subjects with moderate-severe renal disease.
• History of allergic reactionsattributed to Flagyl (metronidazole), which has a chemical structure similar to FMISO.
• Uncontrolled intercurrent illness including, but not limited to symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single Arm Phase 2; Single Arm, Phase II study of Nelfinavir Lead-In (Period 1) Followed by Concurrent Chemoradiation with Nelfinavir (Period 2)	Drug: Nelfinavir (Viracept®) 1250 mg; Period 1: Nelfinavir Lead-In (1250 mg bid, 7-14 days).; Other Names: Nelfinavir Lead-In; Other: Chemoradiation; Period 2: Concurrent Chemoradiation (70 Gy over 7 weeks) with Nelfinavir (1250 mg bid)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Locoregional Control	locoregional control determined via diagnostic imaging and clinical examination.	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Decrease in Hypoxia From Nelfinavir	Decrease in Hypoxia from Nelfinavir was determined by change in uptake and volume as assessed via 18f-FMISO or 18f-EF5 PET/CT pre-Nelfinavir versus post Nelfnavir lead-in	7-14 days
Change in Glucose Metabolism From Nelfinavir	Change in Glucose Metabolism from Nelfinavir was determined by change in glucose uptake as assessed via FDG-PET/CT pre-Nelfinavir versus post Nelfnavir lead-in	From the initiation of any study procedures to 30 days following the completion of 7 chemoradiation

Collaborators and Investigators

• Sponsor: Abramson Cancer Center at Penn Medicine
• Investigators: Principal Investigator: Alexander Lin, MD, Abramson Cancer Center at Penn Medicine

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2014
• Primary Completion (Actual): May 1, 2021
• Study Completion (Actual): May 1, 2022

Study Registration Dates

• First Submitted: July 31, 2014
• First Submitted That Met QC Criteria: August 1, 2014
• First Posted (Estimated): August 4, 2014

Study Record Updates

• Last Update Posted (Actual): July 25, 2023
• Last Update Submitted That Met QC Criteria: June 30, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Head and Neck Neoplasms; Neoplasms, Squamous Cell; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Nelfinavir
• Other Study ID Numbers: UPCC 15313

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No