Radiation Therapy Combined With Paclitaxel and Carboplatin in Treating Patients With Stage III Non-Small Cell Lung Cancer

Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00023673
• Other study ID #: RTOG L-0117
• Secondary ID: CDR0000068850NCI
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: September 13, 2001
• Last updated: November 27, 2017
• Start date: July 2001
• Est. completion date: November 2013

Study information

• Verified date: November 2017
• Source: Radiation Therapy Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 63
• Est. completion date: November 2013
• Est. primary completion date: January 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Cancer
• Lung Neoplasms

Intervention

Drug:
• carboplatin

• paclitaxel

Radiation:
• three-dimensional conformal radiation therapy

Locations

Country	Name	City	State
Canada	Tom Baker Cancer Centre - Calgary	Calgary	Alberta
United States	Summa Center for Cancer Care at Akron City Hospital	Akron	Ohio
United States	Saint Anthony's Hospital at Saint Anthony's Health Center	Alton	Illinois
United States	Ocean Medical Center at Meridian Health	Brick	New Jersey
United States	Providence Saint Joseph Medical Center - Burbank	Burbank	California
United States	Cancer Institute of Cape Girardeau, LLC	Cape Girardeau	Missouri
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Southeast Missouri Regional Cancer Center at Southeast Missouri Hospital	Cape Girardeau	Missouri
United States	Cleveland Clinic Cancer Center at Fairview Hospital	Cleveland	Ohio
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	CCOP - Hematology-Oncology Associates of Central New York	East Syracuse	New York
United States	Alexian Brothers Radiation Oncology	Elk Grove Village	Illinois
United States	Northeast Georgia Medical Center	Gainesville	Georgia
United States	University of Texas Medical Branch	Galveston	Texas
United States	Three Rivers Community Hospital	Grants Pass	Oregon
United States	Oncology Center at Saint Margaret Mercy Healthcare Center	Hammond	Indiana
United States	High Point Regional Hospital	High Point	North Carolina
United States	Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center	La Crosse	Wisconsin
United States	Joe Arrington Cancer Research and Treatment Center	Lubbock	Texas
United States	Dubs Cancer Center at Rogue Valley Medical Center	Medford	Oregon
United States	Providence Cancer Center at PMCC	Medford	Oregon
United States	Medical College of Wisconsin Cancer Center	Milwaukee	Wisconsin
United States	Veterans Affairs Medical Center - Milwaukee	Milwaukee	Wisconsin
United States	Providence Holy Cross Cancer Center	Mission Hills	California
United States	Mobile Infirmary Medical Center	Mobile	Alabama
United States	Good Samaritan Regional Health Center	Mount Vernon	Illinois
United States	Cancer Center at Ball Memorial Hospital	Muncie	Indiana
United States	Bay Medical	Panama City	Florida
United States	Regional Cancer Center at Singing River Hospital	Pascagoula	Mississippi
United States	Albert Einstein Cancer Center	Philadelphia	Pennsylvania
United States	Arizona Oncology Services Foundation	Phoenix	Arizona
United States	Rapid City Regional Hospital	Rapid City	South Dakota
United States	University of California Davis Cancer Center	Sacramento	California
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	CCOP - Cancer Research for the Ozarks	Springfield	Missouri
United States	Hulston Cancer Center at Cox Medical Center South	Springfield	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	Schiffler Cancer Center at Wheeling Hospital	Wheeling	West Virginia
United States	Cancer Treatment Center	Wooster	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Radiation Therapy Oncology Group	National Cancer Institute (NCI)

Countries where clinical trial is conducted

United States,  Canada, 

References & Publications (3)

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 — View 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.

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: p — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maximum Tolerated Dose (MTD) of Three-dimensional Conformal Radiation Therapy (3DRT), in Terms of Gy Per Fraction, Combined With Concurrent Chemotherapy	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 = MTD	From start of treatment to 90 days
Primary	Percentage of Patients Who Survive at Least 12 Months	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%.	From registration to 1 year
Secondary	Frequency of Highest Grade Chemotherapy/Acute RT Toxicities and Late RT Toxicities.	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.	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.)
Secondary	Partial Organ Tolerance Doses for Lung and Esophagus (Percent Volume of Total Lung Receiving > 20 Gy by Toxicity Level)	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.	From start of treatment to last follow-up (Maximum follow-up = 57.9 months.)
Secondary	Partial Organ Tolerance Doses for Lung and Esophagus (Mean Organ Dose by Toxicity Level)	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.	From start of treatment to last follow-up (Maximum follow-up = 57.9 months.)
Secondary	Number of Patients With Complete Response at 3 Months After Completion of Therapy	"Complete response" means no evidence of tumor on the CT scan.	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.