A Phase I/II Trial of ZD1839 (Iressa®) and Rapamycin (Rapamune) in Patients With Advanced Non Small Cell Lung Cancer
18 Years
N/A
Both
Lung Cancer
Trial Information
A Phase I/II Trial of ZD1839 (Iressa®) and Rapamycin (Rapamune) in Patients With Advanced Non Small Cell Lung Cancer
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 Patients withdrawn from study treatment without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.
Inclusion Criteria
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
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Maximum tolerated dose (Phase I)
Safety Issue:
Yes
Principal Investigator
Fairooz F. Kabbinavar, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Jonsson Comprehensive Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
CDR0000401501
NCT ID:
NCT00098462
Start Date:
October 2004
Completion Date:
Related Keywords:
- Lung Cancer
- recurrent non-small cell lung cancer
- stage IIIB non-small cell lung cancer
- stage IV non-small cell lung cancer
- Carcinoma, Non-Small-Cell Lung
- Lung Neoplasms
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