Gefitinib and Sirolimus in Treating Patients With Recurrent or Refractory Stage IIIB or Stage IV Non-Small Cell Lung Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00098462
Recruitment Status : Withdrawn (Withdrawn as study never opened)
First Posted : December 8, 2004
Last Update Posted : October 4, 2012
National Cancer Institute (NCI)
Information provided by:
Jonsson Comprehensive Cancer Center

Brief Summary:

RATIONALE: Gefitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as sirolimus, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Sometimes when chemotherapy is given, it does not stop the growth of tumor cells. The tumor is said to be resistant to chemotherapy. Giving gefitinib together with sirolimus may reduce drug resistance and allow the tumor cells to be killed.

PURPOSE: This phase I/II trial is studying the side effects and best dose of sirolimus when given with gefitinib and to see how well they work in treating patients with recurrent or refractory stage IIIB or stage IV non-small cell lung cancer.

Condition or disease Intervention/treatment Phase
Lung Cancer Drug: gefitinib Drug: sirolimus Phase 1 Phase 2

Detailed Description:



  • Determine the maximum tolerated dose of sirolimus when combined with gefitinib in patients with recurrent or refractory stage IIIB or IV non-small cell lung cancer.


  • Determine the overall response rate (complete response [CR] and partial response [PR]) in patients treated with this regimen.
  • Determine the disease control rate (CR, PR, and stable disease) in patients treated with this regimen.
  • Determine the time to progression and overall survival of patients treated with this regimen.
  • Determine the quality of life of patients treated with this regimen.

OUTLINE: This is an open-label, phase I, dose-escalation study of sirolimus followed by a phase II study.

  • Phase I: Patients receive oral gefitinib once daily and oral sirolimus once daily on days 1-28. Courses repeat every 28 days in the absence of unacceptable toxicity or disease progression.

Cohorts of 3-6 patients receive escalating doses of sirolimus until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

  • Phase II: Patients receive gefitinib and sirolimus as in phase I at the MTD. Quality of life is assessed at baseline, day 1 of each course, and then at 1 month post-progression.

Patients are followed every 9 weeks. Patients withdrawn from study treatment without evidence of disease progression are followed every 6 weeks until disease progression.

PROJECTED ACCRUAL: A total of 25 patients (11 for phase I and 14 for phase II) will be accrued for this study within 8.3 months.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Trial of ZD1839 (Iressa®) and Rapamycin (Rapamune) in Patients With Advanced Non Small Cell Lung Cancer
Study Start Date : October 2004

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer
U.S. FDA Resources

Primary Outcome Measures :
  1. Maximum tolerated dose (Phase I)

Secondary Outcome Measures :
  1. Overall response (complete response [CR] and partial response [PR]) as measured by RECIST criteria
  2. Disease control rate (CR, PR, and stable disease) correlated with smoking history
  3. Time to tumor progression and overall survival
  4. Quality of life as assessed by the Functional Assessment of Cancer Therapy-Lung (FACT-L)
  5. Lung cancer subscale from FACT-L

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Histologically confirmed non-small cell lung cancer

    • Stage IIIB or IV disease
  • Recurrent or refractory disease

    • Received ≥ 1 prior platinum-containing chemotherapy regimen
  • Unidimensionally measurable disease that has not been irradiated
  • No newly diagnosed untreated brain metastases or spinal cord compression
  • Paraffin-embedded tumor tissue or slides available



  • 18 and over

Performance status

  • ECOG 0-2

Life expectancy

  • Not specified


  • Adequate bone marrow function
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3


  • Adequate hepatic function
  • No severe or uncontrolled hepatic disease


  • Adequate renal function
  • Creatinine ≤ 3.0 times upper limit of normal
  • No severe or uncontrolled renal disease


  • Adequate cardiac function
  • No severe or uncontrolled cardiac disease
  • No uncontrolled hyperlipidemia


  • No unstable or uncompensated respiratory disease
  • No clinically active interstitial lung disease

    • Patients with chronic stable radiographic changes who are asymptomatic are eligible


  • Able to take oral medication
  • No gastrointestinal condition (e.g., peptic ulcer disease) that would affect absorption


  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No serious infection
  • No known severe hypersensitivity to gefitinib or any of its excipients
  • No other malignancy within the past 5 years except treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
  • No other severe or uncontrolled systemic disease
  • No significant clinical disorder or laboratory finding that would preclude study participation


Biologic therapy

  • More than 14 days since prior biologic therapy
  • No prior cetuximab, panitumumab, or bevacizumab


  • See Disease Characteristics
  • More than 4 weeks since prior cytotoxic chemotherapy

Endocrine therapy

  • Not specified


  • See Disease Characteristics
  • More than 3 weeks since prior radiotherapy
  • No concurrent radiotherapy


  • Recovered from prior oncologic or other major surgery
  • No prior gastrointestinal surgery affecting absorption
  • No concurrent surgery, including ophthalmic surgery, during and for 1 week after study treatment


  • Recovered from all prior therapy
  • More than 30 days since prior investigational agents
  • No other prior HER1/epidermal growth factor receptor axis agents, including the following:

    • Gefitinib
    • Erlotinib
    • CI-1033
    • Lapatinib
  • No other prior vascular endothelial growth factor axis agents, including the following:

    • ZD6474
    • Vatalanib
  • No concurrent CYP3A4 inducers, including the following:

    • Phenytoin
    • Carbamazepine
    • Rifampin
    • Phenobarbital
    • Barbiturates
    • Hypericum perforatum (St. John's wort)
  • No other concurrent systemic treatment for the malignancy
  • No concurrent bisphosphonates for symptomatic bone metastases
  • No concurrent systemic retinoids

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00098462

Sponsors and Collaborators
Jonsson Comprehensive Cancer Center
National Cancer Institute (NCI)
Study Chair: Fairooz F. Kabbinavar, MD Jonsson Comprehensive Cancer Center Identifier: NCT00098462     History of Changes
Other Study ID Numbers: CDR0000401501
First Posted: December 8, 2004    Key Record Dates
Last Update Posted: October 4, 2012
Last Verified: October 2012

Keywords provided by Jonsson Comprehensive Cancer Center:
recurrent non-small cell lung cancer
stage IIIB non-small cell lung cancer
stage IV non-small cell lung cancer

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action