Clinical trial NCT00003202: Gemcitabine Plus Radiation Therapy or Combination Chemotherapy in Treating Patients With Non-small Cell Lung Cancer
Official title: Alternating Phase I/II Trials of Twice-Weekly Infusion Gemcitabine (2'2'-Difluoro-2'-Deoxycytidine) and Concurrent Thoracic Radiation Alone - Or Following 2 Cycles of Cisplatin/Gemcitabine Induction Chemotherapy for the Treatment of Stage IIIA/IIIB Non Small Cell Lung Cancer (NSCLC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Lung Cancer
Keywords: squamous cell lung cancer
large cell lung cancer
stage IIIA non-small cell lung cancer
stage IIIB non-small cell lung cancer
adenocarcinoma of the lung
adenosquamous cell lung cancer
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-11-26
Enrollment: 40
Sex: ALL
Maximum age (years): 120
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells. Combining radiation therapy with chemotherapy may kill more tumor cells.

PURPOSE: Phase I/II trial to compare the effectiveness of gemcitabine with radiation therapy alone or following two-drug combination chemotherapy in treating patients with stage III non-small cell lung cancer.

Detailed description: OBJECTIVES:

* Determine the maximum tolerated dose of twice-weekly gemcitabine when delivered concurrently with thoracic radiotherapy alone or following 2 cycles of induction chemotherapy in patients with Stage IIIA or IIIB non-small cell lung cancer.
* Assess the toxicity of concurrent thoracic radiation and gemcitabine in these patients.
* Determine the effectiveness of concurrent radiation and gemcitabine by determining the complete response rate, partial response rate, time to recurrence, pattern of recurrence, and overall survival in a cohort of these patients.

OUTLINE: This is an alternating two arm, dose escalation, multicenter study.

Arm I: Patients receive twice-weekly gemcitabine as a 30 minute infusion. Concurrent radiation therapy is administered 5 days a week for 6 weeks.

Arm II: Patients receive 2 cycles of induction chemotherapy consisting of gemcitabine as a 30 minute infusion on day 1 and 8 and cisplatin IV over 1 hour on day 1. Each cycle is 21 days. Patients then receive gemcitabine and radiation therapy as in arm I.

Cohorts of 3 patients are enrolled into each treatment arm at each dose level of gemcitabine. Toxicity for each arm is assessed independently. Once dose limiting toxicity (DLT) is observed at any dose level, 3 more patients are enrolled at the same dose level. The maximum tolerated dose (MTD) is defined as the dose at which no more than 1 of 6 patients experiences grade 4 toxicity, or no more than 4 of 6 patients experience grade 3 or worse toxicity (DLT). After the MTD is determined for each treatment arm, additional patients are treated at that dose level for the phase II portion of the study.

Patients are followed every 3 months for 2 years, then every 4 months for the next 2 years, and then every 6 months thereafter.

PROJECTED ACCRUAL: There will be approximately 24-48 patients accrued into this study within 1-2 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed stage IIIA or IIIB non-small cell lung cancer that is unicentric and inoperable, including the following cellular types:

  * Squamous cell carcinoma
  * Adenocarcinoma
  * Bronchoalveolar carcinoma
  * Large cell anaplastic carcinoma
  * Non-small cell lung cancer not otherwise specified
* Tumors may be multifocal if all of disease is believed to be result of direct spread
* Disease must be fully accessible by radiotherapy ports for the entire prescribed dose
* No supraclavicular nodes or diffuse pleural involvement
* No contralateral hilar disease or an exudative, bloody, or cytologically malignant effusion
* Measurable disease required for phase II of this study

PATIENT CHARACTERISTICS:

Age:

* Any age

Performance status:

* ECOG 0-2

Life expectancy:

* At least 1 year

Hematopoietic:

* Granulocyte count at least 1,500/mm3
* Platelet count at least 100,000/mm3
* Hemoglobin greater than 10 g/dL

Hepatic:

* Bilirubin no greater than 2.0 mg/dL

Renal:

* BUN no greater than 1.5 times normal
* Creatinine no greater than 1.5 times normal

Pulmonary:

* FEV1 no greater than 1 liter except if tumor has negatively impacted
* pulmonary function

Other:

* No other serious medical or psychiatric illness
* No prior lung cancer except if free of disease for more than 3 years
* No other prior malignancy except nonmelanoma skin cancer or if free of
* disease for more than 1 year
* Not pregnant or nursing
* Negative pregnancy test

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* Not specified

Chemotherapy:

* No prior chemotherapy

Endocrine therapy:

* Not specified

Radiotherapy:

* No prior thoracic radiotherapy
* Concurrent radiotherapy to other anatomic sites allowed

Surgery:

* Not specified

Primary outcomes:
measure: •Determine the maximum tolerated dose of twice-weekly gemcitabine when delivered concurrently with thoracic radiotherapy
timeFrame: 6 weeks
Secondary outcomes:
measure: assess the efficacy of dose of twice-weekly gemcitabine when delivered concurrently with thoracic radiotherapy
timeFrame: 72 days
Other outcomes:
Locations:
city: Winston-Salem
country: United States
facility: Comprehensive Cancer Center at Wake Forest University
state: North Carolina
Study officials:
affiliation: Wake Forest University Health Sciences
name: Arthur William Blackstock, MD
role: STUDY_CHAIR
References: