- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00098462
Gefitinib and Sirolimus in Treating Patients With Recurrent or Refractory Stage IIIB or Stage IV Non-Small Cell Lung Cancer
A Phase I/II Trial of ZD1839 (Iressa®) and Rapamycin (Rapamune) in Patients With Advanced Non Small Cell Lung Cancer
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.
Study Overview
Detailed Description
OBJECTIVES:
Primary
- 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.
Secondary
- 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 Patients withdrawn from study treatment without evidence of disease progression are followed every 6 weeks until disease progression.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
Phase
- Phase 2
- Phase 1
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
DISEASE CHARACTERISTICS:
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
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- ECOG 0-2
Life expectancy
- Not specified
Hematopoietic
- Adequate bone marrow function
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
Hepatic
- Adequate hepatic function
- No severe or uncontrolled hepatic disease
Renal
- Adequate renal function
- Creatinine ≤ 3.0 times upper limit of normal
- No severe or uncontrolled renal disease
Cardiovascular
- Adequate cardiac function
- No severe or uncontrolled cardiac disease
- No uncontrolled hyperlipidemia
Pulmonary
- No unstable or uncompensated respiratory disease
No clinically active interstitial lung disease
- Patients with chronic stable radiographic changes who are asymptomatic are eligible
Gastrointestinal
- Able to take oral medication
- No gastrointestinal condition (e.g., peptic ulcer disease) that would affect absorption
Other
- 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
PRIOR CONCURRENT THERAPY:
Biologic therapy
- More than 14 days since prior biologic therapy
- No prior cetuximab, panitumumab, or bevacizumab
Chemotherapy
- See Disease Characteristics
- More than 4 weeks since prior cytotoxic chemotherapy
Endocrine therapy
- Not specified
Radiotherapy
- See Disease Characteristics
- More than 3 weeks since prior radiotherapy
- No concurrent radiotherapy
Surgery
- 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
Other
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Masking: None (Open Label)
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
---|
Maximum tolerated dose (Phase I)
|
Secondary Outcome Measures
Outcome Measure |
---|
Overall response (complete response [CR] and partial response [PR]) as measured by RECIST criteria
|
Disease control rate (CR, PR, and stable disease) correlated with smoking history
|
Time to tumor progression and overall survival
|
Quality of life as assessed by the Functional Assessment of Cancer Therapy-Lung (FACT-L)
|
Lung cancer subscale from FACT-L
|
Collaborators and Investigators
Collaborators
Study record dates
Study Major Dates
Study Start
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
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
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Enzyme Inhibitors
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Anti-Bacterial Agents
- Protein Kinase Inhibitors
- Antibiotics, Antineoplastic
- Antifungal Agents
- Gefitinib
- Sirolimus
Other Study ID Numbers
- CDR0000401501
- UCLA-0407057-01
- ZENECA-IRUSIRES0281
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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