Clinical trial NCT00023673: Radiation Therapy Combined With Paclitaxel and Carboplatin in Treating Patients With Stage III Non-Small Cell Lung Cancer
Official title: A Phase I/II Dose Intensification Study Using Three Dimensional Conformal Radiation Therapy And Concurrent Chemotherapy For Patients With Inoperable, Non-Small Cell Lung Cancer
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: Radiation Therapy Oncology Group
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-04-09
Enrollment: 63
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug and giving them with specialized radiation therapy may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the effectiveness of radiation therapy combined with paclitaxel and carboplatin in treating patients who have stage III non-small cell lung cancer.

Detailed description: OBJECTIVES:

* Determine the maximum tolerated dose of 3-dimensional conformal radiotherapy when administered concurrently with paclitaxel and carboplatin in patients with inoperable stage IIIA or IIIB non-small cell lung cancer. (Phase I) (Closed to accrual as of 01/13/04.)
* Determine the 12-month survival rate in patients treated with this regimen. (Phase II) (Closed to accrual as of 11/27/07.)
* Determine the toxicity of this regimen in these patients.
* Determine the partial organ tolerance doses for the lung and esophagus in patients treated with this regimen.
* Determine the complete response rate in patients treated with this regimen.

OUTLINE: This is a multicenter, dose-escalation study of 3-dimensional conformal radiotherapy.

* Phase I (closed to accrual as of 01/13/04): Patients undergo 3-dimensional conformal radiotherapy once daily five days a week for 7-8 weeks. Patients also receive concurrent chemotherapy comprising paclitaxel IV over 1 hour followed by carboplatin IV over 30 minutes on days 1, 8, 15, 22, 29, 36, and 43.

Cohorts of 7-9 patients receive de-escalating doses of 3-dimensional conformal radiotherapy until the maximum tolerated dose (MTD) is determined when given in combination with chemotherapy. The MTD is defined as the highest dose at which no more than 1 patient experiences dose-limiting toxicity.

* Phase II: Additional patients are accrued and treated as above at the MTD. At least 3 weeks after completing radiotherapy, patients may receive additional chemotherapy comprising paclitaxel IV over 3 hours once and carboplatin IV over 30 minutes once. Treatment with paclitaxel and carboplatin may repeat every 3 weeks for up to 2 courses.

Patients are followed every 3 months for 1 year, every 4 months for 1 year, every 6 months for 3-5 years, and then annually thereafter.

PROJECTED ACCRUAL: A maximum of 73 patients (up to 27 for phase I \[closed to accrual as of 10/28/04\] and 46 for phase II) will be accrued for this study within 1-1.5 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically or cytologically confirmed unresectable stage IIIB non-small cell lung cancer

  * Squamous cell carcinoma
  * Adenocarcinoma
  * Large cell carcinoma
  * Non-small cell carcinoma not otherwise specified
* All detectable primary tumor and involved regional lymph nodes must be encompassed by radiotherapy fields
* Measurable disease on 3-dimensional planning CT scan
* No undifferentiated small cell (oat cell or high-grade neuroendocrine) carcinoma
* No stage IV or recurrent disease
* No distant metastases or supraclavicular lymph node involvement
* No significant atelectasis (i.e., atelectasis of an entire lung)
* No pleural effusions, pericardial effusions, or superior vena cava syndrome
* No lung cancer within the past 2 years
* Ineligible for currently open Radiation Therapy Oncology Group (RTOG) phase III lung protocols

PATIENT CHARACTERISTICS:

Age:

* Not specified

Performance status:

* Zubrod 0-1

Life expectancy:

* Not specified

Hematopoietic:

* Granulocyte count at least 1,500/mm\^3
* Platelet count at least 100,000/mm\^3

Hepatic:

* Bilirubin less than 1.5 mg/dL
* Aspartate aminotransferase (AST) less than 2 times upper limit of normal

Renal:

* Creatinine no greater than 2.0 mg/dL

Pulmonary:

* Forced expiratory volume (FEV)_1 at least 1.0 L

Other:

* Not pregnant or nursing
* Fertile patients must use effective contraception
* No weight loss greater than 5% in the past 6 months
* No other malignancy within the past year except nonmelanoma skin cancer
* Completed 3D plan with total lung V20 \</= 30% mean esophageal dose \</= 34 Gy and esophageal V55 \</= 30%

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* No prior biologic response modifiers for current lung cancer
* At least 5 years since prior biologic response modifiers

Chemotherapy:

* No prior chemotherapy for current lung cancer
* At least 5 years since prior chemotherapy

Endocrine therapy:

* Not specified

Radiotherapy:

* See Disease Characteristics
* No prior radiotherapy to the thorax

Surgery:

* No prior complete tumor resection

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) of Three-dimensional Conformal Radiation Therapy (3DRT), in Terms of Gy Per Fraction, Combined With Concurrent Chemotherapy
timeFrame: From start of treatment to 90 days
measure: Percentage of Patients Who Survive at Least 12 Months
timeFrame: From registration to 1 year
Secondary outcomes:
measure: Frequency of Highest Grade Chemotherapy/Acute RT Toxicities and Late RT Toxicities.
timeFrame: Chemotherapy/Acute RT toxicity: from start of treatment to 90 days from start of study treatment; Late RT toxicity: from 90 days after start of treatment to last follow-up (Maximum follow-up = 57.9 months.)
measure: Partial Organ Tolerance Doses for Lung and Esophagus (Percent Volume of Total Lung Receiving > 20 Gy by Toxicity Level)
timeFrame: From start of treatment to last follow-up (Maximum follow-up = 57.9 months.)
measure: Partial Organ Tolerance Doses for Lung and Esophagus (Mean Organ Dose by Toxicity Level)
timeFrame: From start of treatment to last follow-up (Maximum follow-up = 57.9 months.)
measure: Number of Patients With Complete Response at 3 Months After Completion of Therapy
timeFrame: From start of treatment until 3 months after completion of all study treatment, estimated to be 5 or 6.5 months depending whether or not subject received optional adjuvant chemotherapy.
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Mobile Infirmary Medical Center
state: Alabama
city: Phoenix
country: United States
facility: Arizona Oncology Services Foundation
state: Arizona
city: Burbank
country: United States
facility: Providence Saint Joseph Medical Center - Burbank
state: California
city: Mission Hills
country: United States
facility: Providence Holy Cross Cancer Center
state: California
city: Sacramento
country: United States
facility: University of California Davis Cancer Center
state: California
city: Panama City
country: United States
facility: Bay Medical
state: Florida
city: Gainesville
country: United States
facility: Northeast Georgia Medical Center
state: Georgia
city: Alton
country: United States
facility: Saint Anthony's Hospital at Saint Anthony's Health Center
state: Illinois
city: Elk Grove Village
country: United States
facility: Alexian Brothers Radiation Oncology
state: Illinois
city: Mount Vernon
country: United States
facility: Good Samaritan Regional Health Center
state: Illinois
city: Hammond
country: United States
facility: Oncology Center at Saint Margaret Mercy Healthcare Center
state: Indiana
city: Muncie
country: United States
facility: Cancer Center at Ball Memorial Hospital
state: Indiana
city: Pascagoula
country: United States
facility: Regional Cancer Center at Singing River Hospital
state: Mississippi
city: Cape Girardeau
country: United States
facility: Southeast Missouri Regional Cancer Center at Southeast Missouri Hospital
state: Missouri
city: Cape Girardeau
country: United States
facility: Cancer Institute of Cape Girardeau, LLC
state: Missouri
city: Cape Girardeau
country: United States
facility: Saint Francis Medical Center
state: Missouri
city: Saint Louis
country: United States
facility: CCOP - St. Louis-Cape Girardeau
state: Missouri
city: Saint Louis
country: United States
facility: David C. Pratt Cancer Center at St. John's Mercy
state: Missouri
city: Springfield
country: United States
facility: CCOP - Cancer Research for the Ozarks
state: Missouri
city: Springfield
country: United States
facility: Hulston Cancer Center at Cox Medical Center South
state: Missouri
city: Brick
country: United States
facility: Ocean Medical Center at Meridian Health
state: New Jersey
city: Toms River
country: United States
facility: J. Phillip Citta Regional Cancer Center at Community Medical Center
state: New Jersey
city: Vineland
country: United States
facility: Franklin & Edith Scarpa Regional Cancer Center at South Jersey Healthcare
state: New Jersey
city: East Syracuse
country: United States
facility: CCOP - Hematology-Oncology Associates of Central New York
state: New York
city: High Point
country: United States
facility: High Point Regional Hospital
state: North Carolina
city: Akron
country: United States
facility: Summa Center for Cancer Care at Akron City Hospital
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Cancer Center at Fairview Hospital
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
city: Wooster
country: United States
facility: Cancer Treatment Center
state: Ohio
city: Grants Pass
country: United States
facility: Three Rivers Community Hospital
state: Oregon
city: Medford
country: United States
facility: Dubs Cancer Center at Rogue Valley Medical Center
state: Oregon
city: Medford
country: United States
facility: Providence Cancer Center at PMCC
state: Oregon
city: Philadelphia
country: United States
facility: Albert Einstein Cancer Center
state: Pennsylvania
city: Rapid City
country: United States
facility: Rapid City Regional Hospital
state: South Dakota
city: Galveston
country: United States
facility: University of Texas Medical Branch
state: Texas
city: Lubbock
country: United States
facility: Joe Arrington Cancer Research and Treatment Center
state: Texas
city: Wheeling
country: United States
facility: Schiffler Cancer Center at Wheeling Hospital
state: West 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
state: Wisconsin
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre - Calgary
state: Alberta
Study officials:
affiliation: Mallinckrodt Institute of Radiology at Washington University Medical Center
name: Jeffrey Bradley, MD
role: STUDY_CHAIR
References:
citation: Bradley JD, Bae K, Graham MV, Byhardt R, Govindan R, Fowler J, Purdy JA, Michalski JM, Gore E, Choy H. Primary analysis of the phase II component of a phase I/II dose intensification study using three-dimensional conformal radiation therapy and concurrent chemotherapy for patients with inoperable non-small-cell lung cancer: RTOG 0117. J Clin Oncol. 2010 May 10;28(14):2475-80. doi: 10.1200/JCO.2009.27.1205. Epub 2010 Apr 5.
citation: Bradley JD, Moughan J, Graham MV, Byhardt R, Govindan R, Fowler J, Purdy JA, Michalski JM, Gore E, Choy H. A phase I/II radiation dose escalation study with concurrent chemotherapy for patients with inoperable stages I to III non-small-cell lung cancer: phase I results of RTOG 0117. Int J Radiat Oncol Biol Phys. 2010 Jun 1;77(2):367-72. doi: 10.1016/j.ijrobp.2009.04.029.
citation: Bradley JD, Graham M, Suzanne S, et al.: Phase I results of RTOG L-0117: a phase I/II dose intensification study using 3DCRT and concurrent chemotherapy for patients with inoperable NSCLC. [Abstract] J Clin Oncol 23 (Suppl 16): A-7063, 636s, 2005.