Nelfinavir, Radiation Therapy, Cisplatin, and Etoposide in Treating Patients With Stage III Non-Small Cell Lung Cancer That Cannot Be Removed By Surgery

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2009 by National Cancer Institute (NCI).
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00589056
First received: December 25, 2007
Last updated: June 3, 2009
Last verified: June 2009
  Purpose

RATIONALE: Nelfinavir may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Radiation therapy uses high energy x-rays to kill tumor cells. Nelfinavir may make tumor cells more sensitive to radiation therapy. Drugs used in chemotherapy, such as cisplatin and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving nelfinavir together with radiation therapy, cisplatin, and etoposide may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of nelfinavir when given together with radiation therapy, cisplatin, and etoposide and to see how well they work in treating patients with stage III non-small cell lung cancer that cannot be removed by surgery.


Condition Intervention Phase
Lung Cancer
Drug: cisplatin
Drug: etoposide
Drug: nelfinavir mesylate
Genetic: protein expression analysis
Other: immunohistochemistry staining method
Other: laboratory biomarker analysis
Procedure: biopsy
Radiation: radiation therapy
Phase 1
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Trial of Protease Inhibitor, Nelfinavir, Given With Concurrent Thoracic Chemoradiotherapy in Patients With Locally-Advanced Non-Small Cell Lung Cancer

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Dose-limiting toxicity as measured by NCI Common Toxicity Criteria [ Designated as safety issue: Yes ]
  • Maximum tolerated dose and recommended phase II dose of nelfinavir mesylate [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Response at 3 months after completion of treatment as measured by RECIST criteria [ Designated as safety issue: No ]
  • Overall survival [ Designated as safety issue: No ]
  • Expression of molecular markers (total Akt and p-Akt) in primary tumor or pathologic lymph nodes and in peripheral blood lymphocytes [ Designated as safety issue: No ]

Estimated Enrollment: 42
Study Start Date: June 2007
Estimated Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • 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.

Secondary

  • 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 months.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

  • 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

PRIOR CONCURRENT THERAPY:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00589056

Locations
United States, Pennsylvania
Abramson Cancer Center of the University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104-4283
Contact: Clinical Trials Office - Abramson Cancer Center of the Univers    800-474-9892      
Sponsors and Collaborators
University of Pennsylvania
Investigators
Study Chair: Ramesh Rengan, MD, PhD Abramson Cancer Center of the University of Pennsylvania
  More Information

Additional Information:
No publications provided

Responsible Party: Ramesh Rengan, Abramson Cancer Center of the University of Pennsylvania
ClinicalTrials.gov Identifier: NCT00589056     History of Changes
Other Study ID Numbers: CDR0000582319, UPCC-806285, UPCC-04507
Study First Received: December 25, 2007
Last Updated: June 3, 2009
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
stage IIIA non-small cell lung cancer
stage IIIB non-small cell lung cancer
recurrent non-small cell lung cancer

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Etoposide phosphate
Cisplatin
Etoposide
Nelfinavir
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on September 30, 2014