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A Phase I/II Trial of Protease Inhibitor, Nelfinavir, Given With Concurrent Thoracic Chemoradiotherapy in Patients With Locally-Advanced Non-Small Cell Lung Cancer

Phase 1/Phase 2
18 Years
Open (Enrolling)
Lung Cancer

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Trial Information

A Phase I/II Trial of Protease Inhibitor, Nelfinavir, Given With Concurrent Thoracic Chemoradiotherapy in Patients With Locally-Advanced Non-Small Cell Lung Cancer



- To determine the dose-limiting toxicities, maximum tolerated dose, and recommended
phase II dose of nelfinavir mesylate when administered in combination with concurrent
thoracic radiotherapy, cisplatin, and etoposide in patients with unresectable locally
advanced non-small cell lung cancer.


- To determine the tumor response at 3 months after completion of treatment as measured
by RECIST criteria.

- To assess the inhibition of p-Akt in primary tumor or pathologic lymph nodes and in
peripheral blood lymphocytes after 5-10 days of treatment with nelfinavir mesylate.

- To determine the median overall survival (OS) of patients treated with this regimen.

- To compare the observed median OS of these patients with the historical median OS of 17

OUTLINE: This is a phase I, dose-escalation study of nelfinavir mesylate followed by a phase
II study.

- Phase I: Patients receive oral nelfinavir mesylate twice daily beginning 1-2 weeks
before the initiation of chemoradiotherapy and continuing until the completion of
radiotherapy. Patients undergo thoracic radiotherapy once daily 5 days a week for 7-8
weeks. Patients also receive cisplatin IV on days 1, 8, 29, and 36 and etoposide IV on
days 1-5 and 29-33. After completion of chemoradiotherapy, patients receive two
additional courses of cisplatin and etoposide.

- Phase II: Patients receive nelfinavir mesylate at the maximum tolerated dose determined
in phase I and concurrent chemoradiotherapy as in phase I.

Patients undergo blood sample collection periodically for correlative laboratory studies.
Patients treated in the phase II portion of the study and those with primary tumors or
pathologic lymph nodes easily accessible by core biopsy or mediastinoscopy also undergo
tumor tissue biopsies. Blood and tumor tissue samples are analyzed for expression of
molecular markers (total Akt and p-Akt ) by immunohistochemistry. The molecular markers are
correlated with treatment response.

After completion of study treatment, patients are followed at 3, 6, and 12 months.

Inclusion Criteria


- Histologically confirmed non-small cell lung cancer

- Locally advanced (stage III) disease

- Unresectable disease

- Candidate for concurrent definitive chemotherapy and thoracic radiotherapy, as
determined by the treating physician

- No malignant pleural effusion


- ECOG performance status 0-2

- Absolute neutrophil count > 1,500/mm³

- Platelet count > 100,000/mm³

- Bilirubin ≤ 1.5 mg/dL

- AST or ALT ≤ 2 times upper limit of normal (ULN)

- Creatinine ≤ 1.5 times ULN

- FEV_1 > 600 cc

- Not pregnant or nursing

- Negative pregnancy test

- No weight loss > 10% within the past 6 months

- No known HIV disease


- No prior thoracic radiotherapy

- No prior HIV protease inhibitors

- More than 5 years since prior chemotherapy

- At least 3 weeks since prior exploratory thoracotomy

- No concurrent medications that would preclude nelfinavir administration, including
any of the following:

- Amiodarone

- Quinidine

- Rifampin

- Dihydroergotamine

- Ergonovine

- Ergotamine

- Methylergonovine

- Hypericum perforatum (St. John's wort)

- Lovastatin

- Simvastatin

- Pimozide

- Midazolam

- Triazolam

Type of Study:


Study Design:

Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Dose-limiting toxicity as measured by NCI Common Toxicity Criteria

Safety Issue:


Principal Investigator

Ramesh Rengan, MD, PhD

Investigator Role:

Study Chair

Investigator Affiliation:

Abramson Cancer Center of the University of Pennsylvania



Study ID:




Start Date:

June 2007

Completion Date:

Related Keywords:

  • Lung Cancer
  • stage IIIA non-small cell lung cancer
  • stage IIIB non-small cell lung cancer
  • recurrent non-small cell lung cancer
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms



Abramson Cancer Center of the University of Pennsylvania Philadelphia, Pennsylvania  19104-4283