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A Pilot Trial of Daily Oral ZD1839 (Iressa) With Standard Doses of Carboplatin and Paclitaxel in Patients With Advanced Non-Small Cell Lung Cancer


Phase 1
18 Years
N/A
Not Enrolling
Both
Lung Cancer

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Trial Information

A Pilot Trial of Daily Oral ZD1839 (Iressa) With Standard Doses of Carboplatin and Paclitaxel in Patients With Advanced Non-Small Cell Lung Cancer


OBJECTIVES: I. Determine the maximum tolerated dose of ZD 1839 given intermittently or
continuously and concurrently with standard doses of carboplatin and paclitaxel in patients
with advanced non-small cell lung cancer. II. Determine the safety of ZD 1839 in these
regimens in these patients. III. Determine whether the exposure of either free carboplatin
or paclitaxel in an established treatment regimen is significantly altered by the addition
of oral ZD 1839 in this patient population. IV. Determine the exposure of ZD 1839 before and
after standard doses of carboplatin and paclitaxel to assess whether ZD 1839 steady state is
significantly altered by coadministration of chemotherapy.

OUTLINE: This is an open label, 2 part, multicenter study. Part 1 is a randomized, dose
escalation, 2 period, 2 sequence, crossover design. Part 2 is a nonrandomized, single dose
evaluation design. Part 1: Patients are randomized to receive ZD 1839 beginning 1 week
before either the first (arm I) or second (arm II) course of carboplatin and paclitaxel. Arm
I: Patients receive oral ZD 1839 daily on days 1-14. On day 1 only, ZD 1839 is given twice
at 12 hour intervals. Patients receive paclitaxel IV over 3 hours followed by carboplatin IV
over 30 minutes on days 8 and 36. Subsequent courses consist of ZD 1839 for 14 days and
paclitaxel and carboplatin every 28 days. Arm II: Patients receive paclitaxel and
carboplatin as in arm I on days 1 and 29. Patients receive oral ZD 1839 daily on days 22-35.
On day 22 only, ZD 1839 is given twice at 12 hour intervals. Subsequent courses are
administered as in arm I. Part 2: Patients receive oral ZD 1839 daily on days 1-56. On day 1
only, ZD 1839 is given twice at 12 hour intervals. Patients receive paclitaxel and
carboplatin as in part 1 on days 8 and 36. Subsequent courses consist of ZD 1839
continuously and paclitaxel and carboplatin every 28 days. Treatment continues in both parts
for a maximum of 6 months in the absence of unacceptable toxicity or disease progression. In
both parts 1 and 2, cohorts of 6-12 patients receive escalating doses of ZD 1839 until the
maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at
which 4 of 6 or 4 of 12 patients experience dose limiting toxicities.

PROJECTED ACCRUAL: A maximum of 48 patients will be accrued for this study.

Inclusion Criteria


DISEASE CHARACTERISTICS: Histologically and/or cytologically confirmed advanced or
metastatic non-small cell lung cancer considered incurable with standard surgery or
irradiation No active brain metastases as indicated by clinical symptoms, cerebral edema,
and/or progressive growth

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: WHO 0-1 that has not
worsened within the past 7 days Life expectancy: At least 12 weeks Hematopoietic:
Neutrophil count at least 1,500/mm3 Platelet count at least 100,000/mm3 Hepatic: Bilirubin
no greater than 1.25 times upper limit of normal (ULN) ALT/AST no greater than 2.5 times
ULN (5 times ULN if liver metastases) Renal: Creatinine no greater than 1.25 times ULN No
greater than a trace of blood or protein on urine labstix test Cardiovascular: No prior
history of clinically significant cardiac dysrhythmia, first degree heart block, or other
severe cardiac disease Opthalmologic: No potentially visually threatening epithelial
abnormality of the cornea other than scars, congenital abnormality, or corneal tear film
(e.g., neurotrophic keratitis, corneal edema, or recurrent erosions) No signs and symptoms
of keratoconjunctivitis sicca No concurrent use of contact lenses Other: Not pregnant or
nursing Negative pregnancy test Fertile patients must use effective contraception No other
malignancies within the past 5 years except basal cell carcinoma or carcinoma in situ of
the cervix No evidence of severe or uncontrolled systemic diseases (e.g., hepatitis B,
hepatitis C, or HIV) No known chronic conditions No active dermatoses involving the face
No evidence of any other significant clinical disorder or laboratory finding that would
preclude study participation

PRIOR CONCURRENT THERAPY: Biologic therapy: No prior biologic therapy for non-small cell
lung cancer No concurrent biologic response modifiers Concurrent filgrastim (G-CSF)
allowed only for persistent neutropenia despite dose reductions in prior course
Chemotherapy: No prior chemotherapy for non-small cell lung cancer Endocrine therapy: No
concurrent hormonal therapy No concurrent tamoxifen Radiotherapy: See Disease
Characteristics At least 2 weeks since prior radiotherapy No concurrent radiotherapy
Surgery: See Disease Characteristics Recovered from prior oncologic or other major surgery
Other: No other concurrent anticancer therapy No other concurrent investigational agents
No concurrent drugs with known significant 3A4 inhibitory effects (i.e., ketoconazole,
itraconazole, troleandomycin, erythromycin, diltiazem, verapamil) No concurrent
hydroxychloroquine, amiodarone, or chlorpromazine No concurrent topical eye medication

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Principal Investigator

Vincent A. Miller, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center

Authority:

United States: Federal Government

Study ID:

99-069

NCT ID:

NCT00005806

Start Date:

September 1999

Completion Date:

March 2002

Related Keywords:

  • Lung Cancer
  • recurrent non-small cell lung cancer
  • stage IIIA 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

Name

Location

Memorial Sloan-Kettering Cancer CenterNew York, New York  10021