Study to Evaluate Using Nelfinavir With Chemoradiation for Non-small Cell Lung Cancer

A Phase II Trial of the HIV Protease Inhibitor Nelfinavir and Concurrent Radiation and Chemotherapy in Patients With Stage III Non Small Cell Lung Cancer

This study combines nelfinavir (NFV) with radiation therapy and chemotherapy as a treatment for non-small cell lung cancer (NSCLC) who are considered candidates for pre-operative treatment.

Study Overview

• Status: Terminated
• Conditions: Carcinoma, Non-Small-Cell Lung
• Intervention / Treatment: Drug: Nelfinavir

Detailed Description

This is a phase 2 trial of the HIV protease inhibitor (HPI) Nelfinavir (NFV) in combination with radiotherapy and chemotherapy in patients with locally advanced non-small cell lung cancer (NSCLC) who are considered candidates for pre-operative treatment. This study is to be conducted according to US and international standards of Good Clinical Practice (FDA Title 21 part 312 and International Conference on Harmonization guidelines), applicable government regulations and Institutional research policies and procedures. The endpoints are to determine safety of NFV with chemoradiation, gather preliminary data for response, and tissue specimens for correlative molecular studies. Unacceptable toxicity is unlikely as prior studies have determined dosing 1250 mg twice a day is relatively safe for HIV patients receiving radiation therapy. NFV will start one week prior to chemo-radiotherapy and continue for the duration of chemoradiation (approximately 6 1/2 weeks). Standard radiotherapy (minimum total dose 5040 cGy) and combined (cisplatin/etoposide) chemotherapy based on SWOG 8805 will be delivered in combination with NFV. The thoracic surgery attending physician will determine the feasibility of resection. If the patient has resectable disease, the attending thoracic surgeon will perform the thoracotomy and anatomical resection. If the patient has unresectable disease, subject will be followed for 30 days post NFV administration. After the initial 30 days post-NFV, subjects will be followed for long-term outcomes (disease response and overall survival). Adjuvant therapy may be continued off-study at the discretion of managing oncology personnel. Tumors obtained at the time of surgical resection will be assessed for pathological response. Tumor tissue taken pre-treatment will be assessed for markers that may predict response such as Akt, VEGF, and EGFR.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • The University of Iowa Department of Radiation Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Histological diagnosis of non-small cell lung cancer that is Stage III (T1-3, pN2, M0) NSCLC in whom neoadjuvant therapy is recommended.
• Must have had a mediastinoscopy to determine nodal status and potential resectability
• Must have enough tissue from the biopsy for tissue marker determination for correlative studies
• Negative metastatic work up (FDG PET/CT, brain CT or MRI)
• No prior thoracic radiotherapy will be permitted
• Age 18 years or greater
• ECOG performance status 0-1 (Karnofsky at least 70%)
• Normal organ and marrow function
• No known HIV infection
• Not pregnant
• Ability to understand and the willingness to sign an informed consent document

Exclusion Criteria:

• Patients requiring a pneumonectomy
• Patients who have had chemotherapy or radiation therapy within 4 weeks prior to entering the study, or who have not recovered from adverse events due to agents administered earlier.
• Prior thoracic radiation
• Treatment with any other investigational agents.
• Known metastases
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to NFV
• Patients receiving drugs contraindicated with NFV will be excluded.
• Uncontrolled, intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study compliance.
• Pregnant or lactating women
• HIV-positive patients on combination antiretroviral therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• 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: Nelfinavir	Drug: Nelfinavir; 1250 mg twice daily starting for approximately 6.5 weeks.; Other Names: Viracept

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Pathologic Complete Response	30 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Characterization of Overall and Disease-free Survival	long-term
Safety and Tolerability of the Combined Treatment Regimen	7 weeks

Collaborators and Investigators

• Sponsor: University of Iowa

Study record dates

Study Major Dates

• Study Start: August 1, 2008
• Primary Completion (Actual): March 1, 2011
• Study Completion (Actual): March 1, 2011

Study Registration Dates

• First Submitted: November 13, 2008
• First Submitted That Met QC Criteria: November 13, 2008
• First Posted (Estimate): November 14, 2008

Study Record Updates

• Last Update Posted (Actual): July 28, 2017
• Last Update Submitted That Met QC Criteria: June 29, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: chemotherapy; NSCLC; radiation therapy; NFV; nelfinavir
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; 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: 200802788

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Terminated due to poor enrollment; lack of data to share.

Drug and device information, study documents

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