Clinical trial NCT00016315: Gemcitabine, Carboplatin or Paclitaxel Plus Radiation Therapy in Treating Patients With Stage IIIA or IIIB Non-Small Cell Lung Cancer
Official title: A Phase I Study of Gemcitabine, Carboplatin or Gemcitabine, Paclitaxel and Radiation Therapy Followed by Adjuvant Chemotherapy for Patients With Favorable Prognosis Inoperable Stage IIIA/B Non-Small Cell Lung Cancer (NSCLC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Lung Cancer
Keywords: stage IIIA non-small cell lung cancer
stage IIIB non-small cell lung cancer
Lead sponsor: Radiation Therapy Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-05-07
Enrollment: 35
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: RATIONALE: Drugs used in chemotherapy, such as gemcitabine, carboplatin, and paclitaxel, work in 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 trial to study the effectiveness of combining combination chemotherapy with radiation therapy in treating patients who have stage IIIA or stage IIIB non-small cell lung cancer.

Detailed description: OBJECTIVES:

* Determine the maximum tolerated dose (MTD) of gemcitabine when administered with carboplatin and thoracic radiotherapy followed by adjuvant gemcitabine and carboplatin in patients with stage IIIA or IIIB non-small cell lung cancer.
* Determine the MTD of gemcitabine and paclitaxel when administered with thoracic radiotherapy followed by adjuvant gemcitabine and carboplatin in these patients.

OUTLINE: This is a multicenter, dose-escalation study of gemcitabine and paclitaxel. Patients are sequentially assigned to 1 of 3 treatment regimens.

* Regimen A: Patients receive gemcitabine IV over 30-60 minutes on days 1, 8, 22, 29, and 43 and thoracic radiotherapy daily 5 days a week for 7 weeks beginning on day 1.
* Regimen B (closed to accrual as of 5/13/03): Patients receive gemcitabine and thoracic radiotherapy as in regimen A and carboplatin IV over 30 minutes on days 1, 8, 22, 29, and 43.
* Regimen C: Patients receive gemcitabine and thoracic radiotherapy as in regimen A and paclitaxel IV over 1 hour on days 1, 8, 22, 29, and 43.

At 3 weeks after completion of chemoradiotherapy, all patients receive adjuvant gemcitabine IV over 30-60 minutes on days 71, 78, 92, and 99 and carboplatin IV over 30 minutes on days 71 and 92.

The first 6 patients enrolled receive regimen A to determine the safety of the initial dose of gemcitabine. After completion of regimen A, cohorts of 3-6 patients receive escalating doses of gemcitabine in regimen B (closed to accrual as of 5/13/03) until the maximum tolerated dose (MTD) is determined. In a separate sequence, cohorts of 3-6 patients receive alternating escalating doses of gemcitabine and paclitaxel in regimen C until the MTD is determined. The MTD is defined as the dose preceding that at which at least 3 of 6 patients experience dose-limiting toxicity.

Patients are followed at 3 months, 6 months, every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A maximum of 78 patients will be accrued for this study within 29 months.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed loco-regionally advanced non-small cell lung cancer meeting one of the following staging criteria:

  * Medically inoperable stage IIIA
  * Unresectable stage IIIA or IIIB
* Measurable disease on three-dimensional planning CT scan
* No post-resection intrathoracic tumor recurrence
* No pleural effusion on chest x-ray except those occurring after attempted thoracotomy or other invasive thoracic procedure
* No evidence of small cell histology
* No evidence of hematogenous or distant metastases

PATIENT CHARACTERISTICS:

Age:

* Not specified

Performance status:

* Zubrod 0-1

Life expectancy:

* Not specified

Hematopoietic:

* Platelet count at least 100,000/mm\^3
* Absolute granulocyte count at least 2,000/mm\^3
* Hemoglobin at least 8.0 g/dL

Hepatic:

* Bilirubin no greater than 1.5 mg/dL
* Serum glutamate oxaloacetate transaminase (SGOT) no greater than 1.5 times upper limit of normal (unless caused by documented benign disease)

Renal:

* Creatinine no greater than 1.5 mg/dL

Cardiovascular:

* No myocardial infarction within the past 6 months
* No symptomatic heart disease, including angina, congestive heart failure, or uncontrolled arrhythmia

Pulmonary:

* Forced expiratory volume (FEV)_1 greater than 1,000 mL

Other:

* No other invasive malignancy within the past 3 years except nonmelanoma skin cancer
* No weight loss of more than 10% in 3 months prior to diagnosis
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* Not specified

Chemotherapy:

* No prior chemotherapy

Endocrine therapy:

* Not specified

Radiotherapy:

* No prior thoracic or neck radiotherapy

Surgery:

* See Disease Characteristics
* No prior complete or subtotal tumor resection

Primary outcomes:
measure: To determine the maximum tolerated dose of gemcitabine with carboplatin-based chemotherapy and radiation therapy
timeFrame: From start of treatment to 90 days
measure: To determine the maximum tolerated dose of gemcitabine with paclitaxel-based chemotherapy and radiation therapy
timeFrame: From start of treatment to 90 days
Secondary outcomes:
Other outcomes:
Locations:
city: Oakland
country: United States
facility: CCOP - Bay Area Tumor Institute
state: California
city: Miami
country: United States
facility: University of Miami Sylvester Comprehensive Cancer Center
state: Florida
city: Dubuque
country: United States
facility: Wendt Regional Cancer Center of Finley Hospital
state: Iowa
city: Long Branch
country: United States
facility: Monmouth Medical Center
state: New Jersey
city: Akron
country: United States
facility: Akron City Hospital
state: Ohio
city: Salem
country: United States
facility: Cancer Care Center, Incorporated
state: Ohio
city: Drexel Hill
country: United States
facility: Delaware County Memorial Hospital
state: Pennsylvania
city: East Stroudsburg
country: United States
facility: Dale and Frances Hughes Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Mercy Hospital of Pittsburgh
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center at Vanderbilt Medical Center
state: Tennessee
city: Murray
country: United States
facility: Cottonwood Hospital Medical Center
state: Utah
city: Ogden
country: United States
facility: McKay-Dee Hospital Center
state: Utah
city: Provo
country: United States
facility: Utah Valley Regional Medical Center - Provo
state: Utah
city: Saint George
country: United States
facility: Dixie Regional Medical Center
state: Utah
city: Salt Lake City
country: United States
facility: LDS Hospital
state: Utah
city: Danville
country: United States
facility: Danville Regional Medical Center
state: Virginia
city: La Crosse
country: United States
facility: Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Medical College of Wisconsin Cancer Center
state: Wisconsin
city: Milwaukee
country: United States
facility: Veterans Affairs Medical Center - Milwaukee (Zablocki)
state: Wisconsin
Study officials:
affiliation: Simmons Cancer Center
name: Hak Choy, MD
role: STUDY_CHAIR
References:
citation: Choy H, Jain AK, Moughan J, Curran W, Whipple G, Demas WF, Ettinger DS. RTOG 0017: a phase I trial of concurrent gemcitabine/carboplatin or gemcitabine/paclitaxel and radiation therapy ("ping-pong trial") followed by adjuvant chemotherapy for patients with favorable prognosis inoperable stage IIIA/B non-small cell lung cancer. J Thorac Oncol. 2009 Jan;4(1):80-6. doi: 10.1097/JTO.0b013e318191503f.
citation: Choy H, Swann S, Curran W, et al.: A phase I trial of gemcitabine, carboplatin or gemcitabine, paclitaxel and concurrent radiation therapy followed by consolidative gemcitabine and carboplatin for inoperable stage III non-small cell lung cancer: an RTOG 0017 study. [Abstract] Int J Radiat Oncol Biol Phys 63 (2 Suppl 1): A-70, S42, 2005.
citation: Choy H, Swann S, Walter C, et al.: A phase I trial of gemcitabine, carboplatin or gemcitabine, paclitaxel and concurrent radiation therapy followed by consolidative gemcitabine and carboplatin for inoperable stage III non-small cell lung cancer: an RTOG study. [Abstract] J Clin Oncol 23 (Suppl 16): A-7103, 646s, 2005.