Radiation Therapy Combined With Paclitaxel and Carboplatin in Treating Patients With Stage III Non-Small Cell Lung Cancer
- Conditions
- Lung Cancer
- Interventions
- Registration Number
- NCT00023673
- Lead Sponsor
- Radiation Therapy Oncology Group
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 63
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Phase I: 75.25 Gy/36 fx + chemotherapy carboplatin Phase I: Three-dimensional conformal radiation therapy (3DRT) of 75.25 Gy given in 36 fractions (2.15 Gy per fraction) with concurrent chemotherapy consisting of weekly paclitaxel at 50mg/m2 and carboplatin at area under the curve 2mg/m2. Adjuvant systemic chemotherapy (two cycles of paclitaxel and carboplatin) following completion of RT was optional. Phase I: 75.25 Gy/36 fx + chemotherapy paclitaxel Phase I: Three-dimensional conformal radiation therapy (3DRT) of 75.25 Gy given in 36 fractions (2.15 Gy per fraction) with concurrent chemotherapy consisting of weekly paclitaxel at 50mg/m2 and carboplatin at area under the curve 2mg/m2. Adjuvant systemic chemotherapy (two cycles of paclitaxel and carboplatin) following completion of RT was optional. Phase I: 75.25 Gy/36 fx + chemotherapy three-dimensional conformal radiation therapy Phase I: Three-dimensional conformal radiation therapy (3DRT) of 75.25 Gy given in 36 fractions (2.15 Gy per fraction) with concurrent chemotherapy consisting of weekly paclitaxel at 50mg/m2 and carboplatin at area under the curve 2mg/m2. Adjuvant systemic chemotherapy (two cycles of paclitaxel and carboplatin) following completion of RT was optional. Phase I: 74 Gy/37 fx + chemotherapy carboplatin Phase I: Three-dimensional conformal radiation therapy (3DRT) of 74 Gy given in 37 fractions (2.0 Gy per fraction) with concurrent chemotherapy consisting of weekly paclitaxel at 50mg/m2 and carboplatin at area under the curve 2mg/m2. Adjuvant systemic chemotherapy (two cycles of paclitaxel and carboplatin) following completion of RT was optional. Phase I: 74 Gy/37 fx + chemotherapy paclitaxel Phase I: Three-dimensional conformal radiation therapy (3DRT) of 74 Gy given in 37 fractions (2.0 Gy per fraction) with concurrent chemotherapy consisting of weekly paclitaxel at 50mg/m2 and carboplatin at area under the curve 2mg/m2. Adjuvant systemic chemotherapy (two cycles of paclitaxel and carboplatin) following completion of RT was optional. Phase I: 74 Gy/37 fx + chemotherapy three-dimensional conformal radiation therapy Phase I: Three-dimensional conformal radiation therapy (3DRT) of 74 Gy given in 37 fractions (2.0 Gy per fraction) with concurrent chemotherapy consisting of weekly paclitaxel at 50mg/m2 and carboplatin at area under the curve 2mg/m2. Adjuvant systemic chemotherapy (two cycles of paclitaxel and carboplatin) following completion of RT was optional. Phase I: 70 Gy/35 fx + chemotherapy carboplatin Phase I: Three-dimensional conformal radiation therapy (3DRT) of 70 Gy given in 35 fractions (2.0 Gy per fraction) with concurrent chemotherapy consisting of weekly paclitaxel at 50mg/m2 and carboplatin at area under the curve 2mg/m2. Adjuvant systemic chemotherapy (two cycles of paclitaxel and carboplatin) following completion of RT was optional. Phase I: 70 Gy/35 fx + chemotherapy paclitaxel Phase I: Three-dimensional conformal radiation therapy (3DRT) of 70 Gy given in 35 fractions (2.0 Gy per fraction) with concurrent chemotherapy consisting of weekly paclitaxel at 50mg/m2 and carboplatin at area under the curve 2mg/m2. Adjuvant systemic chemotherapy (two cycles of paclitaxel and carboplatin) following completion of RT was optional. Phase I: 70 Gy/35 fx + chemotherapy three-dimensional conformal radiation therapy Phase I: Three-dimensional conformal radiation therapy (3DRT) of 70 Gy given in 35 fractions (2.0 Gy per fraction) with concurrent chemotherapy consisting of weekly paclitaxel at 50mg/m2 and carboplatin at area under the curve 2mg/m2. Adjuvant systemic chemotherapy (two cycles of paclitaxel and carboplatin) following completion of RT was optional. Phase II: 74 Gy/37 fx + chemotherapy paclitaxel Phase II: Three-dimensional conformal radiation therapy (3DRT) of 74 Gy given in 37 fractions (2.0 Gy per fraction) with concurrent chemotherapy consisting of weekly paclitaxel at 50mg/m2 and carboplatin at area under the curve 2mg/m2. Adjuvant systemic chemotherapy (two cycles of paclitaxel and carboplatin) following completion of RT was optional. Phase II: 74 Gy/37 fx + chemotherapy three-dimensional conformal radiation therapy Phase II: Three-dimensional conformal radiation therapy (3DRT) of 74 Gy given in 37 fractions (2.0 Gy per fraction) with concurrent chemotherapy consisting of weekly paclitaxel at 50mg/m2 and carboplatin at area under the curve 2mg/m2. Adjuvant systemic chemotherapy (two cycles of paclitaxel and carboplatin) following completion of RT was optional. Phase II: 74 Gy/37 fx + chemotherapy carboplatin Phase II: Three-dimensional conformal radiation therapy (3DRT) of 74 Gy given in 37 fractions (2.0 Gy per fraction) with concurrent chemotherapy consisting of weekly paclitaxel at 50mg/m2 and carboplatin at area under the curve 2mg/m2. Adjuvant systemic chemotherapy (two cycles of paclitaxel and carboplatin) following completion of RT was optional.
- Primary Outcome Measures
Name Time Method Maximum Tolerated Dose (MTD) of Three-dimensional Conformal Radiation Therapy (3DRT), in Terms of Gy Per Fraction, Combined With Concurrent Chemotherapy From start of treatment to 90 days Dose limiting toxicity (DLT) = Grade 3/4 non-hematologic toxicities (excluding nausea, vomiting, and alopecia) and Grade 4 hematologic toxicities. The DLT rate for this study was set at 40% based on Radiation Therapy Oncology Group (RTOG) study 94-10. No acute (within 90 days from start of 3DRT) DLT's in the first 5 patients (0/5) or the combination of one acute DLT in the first 5 patients (1/5) and none in the next 2 patients (0/2) was required to deem a given dose level to be acceptable. If at any time a Grade 5 toxicity (death) occurred, accrual would be suspended and the event reviewed by a study chair. At any given dose level, this design gives at least 90% confidence that the true acute DLT rate is less than 40% and the probability of not escalating when the true toxicity rate is 40% or higher is at least 83%.
Rating scale: 0 = not the MTD, 1 = MTDPercentage of Patients Who Survive at Least 12 Months From registration to 1 year Null hypothesis: p\<= 62.3% (the best arm of RTOG 94-10); alternative hypothesis: p\>= 77.9%. Where p is the percentage of patients alive at at 12 months. Using a one-group chi-square test with alpha = 0.10, a sample size of 50 patients provides at least 87% power to detect a 25% or greater relative increase in the 12-month survival rate, or equivalently, an absolute increase of at least 15.6 percentage points (62.3 versus 77.9). If the point estimate is greater than 71.1% (upper bound), then the conclusion is that the 12-month survival rate from the new treatment significantly improved from 62.3%.
- Secondary Outcome Measures
Name Time Method Number of Patients With Complete Response at 3 Months After Completion of Therapy 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. "Complete response" means no evidence of tumor on the CT scan.
Frequency of Highest Grade Chemotherapy/Acute RT Toxicities and Late RT Toxicities. 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.) Highest grade toxicity per subject was counted. Toxicities were graded using the Common Toxicity Criteria (CTC) v 2.0 for chemotherapy/acute RT toxicities and using the RTOG/EORTC Late Toxicity Criteria for late RT toxicity. Grade refers to the severity of the toxicity. Both criteria assign Grades 1 through 5 with unique clinical descriptions of severity for a given toxicity based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to toxicity.Chemotherapy/Acute RT toxicities occur during chemotherapy and/or within 90 days of the start of RT. Late RT toxicities occur more than 90 days after the start of RT.
Partial Organ Tolerance Doses for Lung and Esophagus (Percent Volume of Total Lung Receiving > 20 Gy by Toxicity Level) From start of treatment to last follow-up (Maximum follow-up = 57.9 months.) Percent volume of total lung receiving \> 20 Gy radiation therapy (Lung V20) was compared between the two patient groups of those who experienced a grade 3 and higher lung toxicity and those who did not. Similarly, it was also compared between the two patient groups of those who experienced a grade 2 and higher esophageal toxicity and those who did not. Toxicities graded using CTC v 2.0 for chemotherapy/acute RT toxicities and using the RTOG/EORTC Late Toxicity Criteria for late RT toxicity. Grade refers to the severity of the toxicity. Both criteria assign Grades 1 through 5 with unique clinical descriptions of severity for a given toxicity based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to toxicity.
Partial Organ Tolerance Doses for Lung and Esophagus (Mean Organ Dose by Toxicity Level) From start of treatment to last follow-up (Maximum follow-up = 57.9 months.) Mean lung dose was compared between the two patient groups of those who experienced a grade 3 and higher lung toxicity and those who did not. Similarly, mean lung dose, and mean esophageal dose were compared between the two patient groups of those who experienced a grade 2 and higher esophageal toxicity and those who did not. Toxicities graded using CTC v 2.0 for chemotherapy/acute RT toxicities and using the RTOG/EORTC Late Toxicity Criteria for late RT toxicity. Grade refers to the severity of the toxicity. Both criteria assign Grades 1 through 5 with unique clinical descriptions of severity for a given toxicity based on this general guideline: Grade 1 Mild, Grade 2 Moderate, Grade 3 Severe, Grade 4 Life-threatening or disabling, Grade 5 Death related to toxicity.
Trial Locations
- Locations (41)
Mobile Infirmary Medical Center
🇺🇸Mobile, Alabama, United States
Good Samaritan Regional Health Center
🇺🇸Mount Vernon, Illinois, United States
CCOP - Cancer Research for the Ozarks
🇺🇸Springfield, Missouri, United States
CCOP - Hematology-Oncology Associates of Central New York
🇺🇸East Syracuse, New York, United States
Cleveland Clinic Cancer Center at Fairview Hospital
🇺🇸Cleveland, Ohio, United States
Albert Einstein Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Arizona Oncology Services Foundation
🇺🇸Phoenix, Arizona, United States
Providence Holy Cross Cancer Center
🇺🇸Mission Hills, California, United States
Bay Medical
🇺🇸Panama City, Florida, United States
Providence Saint Joseph Medical Center - Burbank
🇺🇸Burbank, California, United States
University of California Davis Cancer Center
🇺🇸Sacramento, California, United States
Northeast Georgia Medical Center
🇺🇸Gainesville, Georgia, United States
Saint Anthony's Hospital at Saint Anthony's Health Center
🇺🇸Alton, Illinois, United States
Hulston Cancer Center at Cox Medical Center South
🇺🇸Springfield, Missouri, United States
High Point Regional Hospital
🇺🇸High Point, North Carolina, United States
Three Rivers Community Hospital
🇺🇸Grants Pass, Oregon, United States
Ocean Medical Center at Meridian Health
🇺🇸Brick, New Jersey, United States
Oncology Center at Saint Margaret Mercy Healthcare Center
🇺🇸Hammond, Indiana, United States
Alexian Brothers Radiation Oncology
🇺🇸Elk Grove Village, Illinois, United States
Regional Cancer Center at Singing River Hospital
🇺🇸Pascagoula, Mississippi, United States
Cancer Center at Ball Memorial Hospital
🇺🇸Muncie, Indiana, United States
Southeast Missouri Regional Cancer Center at Southeast Missouri Hospital
🇺🇸Cape Girardeau, Missouri, United States
Cancer Institute of Cape Girardeau, LLC
🇺🇸Cape Girardeau, Missouri, United States
Saint Francis Medical Center
🇺🇸Cape Girardeau, Missouri, United States
CCOP - St. Louis-Cape Girardeau
🇺🇸Saint Louis, Missouri, United States
David C. Pratt Cancer Center at St. John's Mercy
🇺🇸Saint Louis, Missouri, United States
J. Phillip Citta Regional Cancer Center at Community Medical Center
🇺🇸Toms River, New Jersey, United States
Franklin & Edith Scarpa Regional Cancer Center at South Jersey Healthcare
🇺🇸Vineland, New Jersey, United States
Summa Center for Cancer Care at Akron City Hospital
🇺🇸Akron, Ohio, United States
Cleveland Clinic Taussig Cancer Center
🇺🇸Cleveland, Ohio, United States
Cancer Treatment Center
🇺🇸Wooster, Ohio, United States
Providence Cancer Center at PMCC
🇺🇸Medford, Oregon, United States
Dubs Cancer Center at Rogue Valley Medical Center
🇺🇸Medford, Oregon, United States
University of Texas Medical Branch
🇺🇸Galveston, Texas, United States
Rapid City Regional Hospital
🇺🇸Rapid City, South Dakota, United States
Joe Arrington Cancer Research and Treatment Center
🇺🇸Lubbock, Texas, United States
Medical College of Wisconsin Cancer Center
🇺🇸Milwaukee, Wisconsin, United States
Schiffler Cancer Center at Wheeling Hospital
🇺🇸Wheeling, West Virginia, United States
Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center
🇺🇸La Crosse, Wisconsin, United States
Veterans Affairs Medical Center - Milwaukee
🇺🇸Milwaukee, Wisconsin, United States
Tom Baker Cancer Centre - Calgary
🇨🇦Calgary, Alberta, Canada