Brief Title
Combination Chemotherapy, Radiation Therapy, and Gefitinib in Treating Patients With Stage III Non-Small Cell Lung Cancer
Official Title
ZD1839 (NSC #715055, IND #61187) With Induction Paclitaxel And Carboplatin Followed By Either Radiation Or Concomitant Radiation With Weekly Paclitaxel And Carboplatin In Stage III Non-Small Cell Lung Cancer, A Phase II Study
Brief Summary
This phase II clinical trial studies how well combining different regimens of chemotherapy
and gefitinib with radiation therapy work in treating patients with stage III non-small cell
lung cancer. Drugs used in chemotherapy work in different ways to stop the growth of tumor
cells, either by killing the cells or by stopping them from dividing. Biological therapies
such as gefitinib may interfere with the growth of tumor cells and slow the growth of
non-small cell lung cancer. Radiation therapy uses high-energy x-rays to damage tumor cells.
Giving different regimens of combination therapy together with gefitinib and radiation
therapy may be an effective treatment for non-small cell lung cancer.
Detailed Description
PRIMARY OBJECTIVES:
I. To determine whether ZD1839 (gefitinib) at 250 mg orally every day administered
concomitantly with radiotherapy after induction treatment consisting of paclitaxel,
carboplatin, and ZD1839 among patients with inoperable stage III non-small cell lung cancer
and Common Terminology Criteria (CTC) performance status 2 or poor risk performance status
0-1 is tolerable.
II. To determine whether ZD1839 at 250 mg orally every day administered concomitantly with
paclitaxel, carboplatin, and radiation after induction treatment consisting of paclitaxel,
carboplatin, and ZD1839 among patients with inoperable stage III non-small cell lung cancer
and CTC performance status 0-1 is tolerable.
III. To determine the overall response rate, failure-free survival, and survival after
treatment with induction chemotherapy with daily ZD1839, concomitant radiotherapy and daily
ZD1839, and post-radiotherapy single agent daily ZD1839 among patients with CTC performance
status 2 or poor risk performance status 0-1 and inoperable stage III non-small cell lung
cancer.
IV. To determine the overall response rate, failure-free survival, and survival after
treatment with induction chemotherapy and daily ZD1839, concomitant chemoradiotherapy and
daily ZD1839, and post-radiotherapy single agent daily ZD1839 among patients with CTC
performance status 0-1 and inoperable stage III non-small cell lung cancer.
V. To determine if elevated circulating epidermal growth factor receptor (EGFR) levels prior
to treatment, as determined by either quantitative polymerase chain reaction (PCR) or direct
enzyme-linked immunosorbent assay (ELISA) measurement, may predict for response to therapy
with EGFR inhibitors.
OUTLINE:
All patients receive induction therapy comprising paclitaxel IV over 3 hours followed by
carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for 2 courses.
Patients then receive therapy based on their assigned stratum.
STRATUM I: Patients receive gefitinib orally (PO) daily for 7 weeks. Patients also undergo
concurrent radiotherapy once daily 5 days a week for 7 weeks.
STRATUM II: Patients receive gefitinib and radiotherapy as in stratum I concurrently with
paclitaxel IV over 1 hour followed by carboplatin over 30 minutes once weekly for 7 weeks.
Patients then receive gefitinib PO daily in the absence of disease progression or
unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 1 year and
then every 6 months for 2 years.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Overall survival (Stratum I)
Condition
Adenocarcinoma of the Lung
Intervention
paclitaxel
Study Arms / Comparison Groups
Stratum I (gefitinib, radiotherapy)
Description: Patients receive gefitinib orally (PO) daily for 7 weeks. Patients also undergo concurrent radiotherapy once daily 5 days a week for 7 weeks. Patients then receive gefitinib PO daily in the absence of disease progression or unacceptable toxicity.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
144
Start Date
May 2002
Primary Completion Date
March 2006
Eligibility Criteria
Inclusion Criteria:
- Histologically or cytologically documented non-small cell lung cancer (NSCLC),
including squamous cell carcinoma, adenocarcinoma (including bronchoalveolar cell),
and large cell anaplastic carcinoma (including giant and clear cell carcinomas)
- ELIGIBLE DISEASE STAGES: Inoperable IIIA and selected IIIB
- Generally, patients entered must be considered unresectable or inoperable;
patients with T1 or T2, N2 disease are eligible; patients with T3, N2 or T4,
N0-N2 disease are eligible if based on the closeness to the carina, invasion of
the mediastinum or invasion of the chest wall; patients with T3, N0-N1 disease
are not eligible; patients must be M0 (M1 patients are not eligible)
- Patients with direct invasion of vertebral body are ineligible
- Patients with tumors adjacent to a vertebral body are eligible, unless there
is demonstrable bone invasion, as long as all gross disease can be
encompassed in the radiation boost field in accordance with the homogeneity
criteria
- Patients with contralateral mediastinal disease (N3) are eligible if all
gross disease can be encompassed in the radiation boost field in accordance
with the homogeneity criteria; patients with scalene, supraclavicular, or
contralateral hilar node involvement are ineligible
- Patients with a pleural effusion, which is a transudate, cytologically
negative and non-bloody, are eligible if the radiation oncologist feels the
tumor can be encompassed within a reasonable field of radiotherapy. Patients
with exudative, bloody, or cytologically malignant effusions are not
eligible; if a pleural effusion can be seen on the chest computed tomography
(CT) but not on chest x-ray (CXR) and is too small to tap, the patient will
be eligible; a pleural effusion appearing only after a thoracotomy or other
invasive thoracic procedure was attempted will not make a patient ineligible
- PATIENTS MUST HAVE MEASURABLE DISEASE
- Lesions that can be accurately measured in at least one dimension (longest
diameter to be recorded) as >= 20 mm with conventional techniques or as ≥10 mm
with spiral CT scan
- Lesions that are not considered measurable include the following:
- Bone lesions
- Leptomeningeal disease
- Ascites
- Pleural/pericardial effusion
- Abdominal masses that are not confirmed and followed by imaging techniques
- Cystic lesions
- Tumor lesions situated in a previously irradiated area
- PRIOR THERAPY
- >= 2 weeks since formal exploratory thoracotomy.
- No prior chemotherapy or radiation therapy for NSCLC
- CTC performance status 0-2
- No "currently active" second malignancy other than non-melanoma skin cancers; patients
are not considered to have a "currently active" malignancy if they have completed
therapy and are considered by their physician to be at less than 30% risk of relapse
- Non-pregnant and non-nursing because of significant risk to the fetus/infant
- No patients with uncontrolled intercurrent illness including, but not limited to,
ongoing or active infection, symptomatic congestive heart failure, unstable angina
pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would
limit compliance with study requirements
- No patients with chronic gastrointestinal disorders including liver disease, diarrheal
or emetic disorders, or malabsorptive conditions which could worsen toxicity or limit
efficacy of ZD1839
- No cytochrome P450 3A4 (CYP3A4) inducers within 7 days prior to starting protocol
therapy and while on protocol treatment. CYP3A4 inducers: phenytoin, carbamazepine,
barbiturates, rifampicin, dexamethasone, and St John's Wort; single doses of
dexamethasone used as an antiemetic are permitted
- No human immunodeficiency virus (HIV)-positive patients receiving combination
anti-retroviral therapy
- Granulocytes >= 1,500/ul
- Platelets >= 100,000/ul
- Calculated creatinine clearance >= 20 cc/min
- Bilirubin < 1.5 mg/dl
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) < 2
x upper limit of normal (ULN)
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Neal Ready, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT00040794
Organization ID
NCI-2012-02821
Secondary IDs
CALGB-30106
Responsible Party
Sponsor
Study Sponsor
National Cancer Institute (NCI)
Study Sponsor
Neal Ready, Principal Investigator, Cancer and Leukemia Group B
Verification Date
June 2013