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

NCT00023673 | Completed Phase 1 Results

• 3 other identifiers: RTOG L-0117CDR0000068850NCI-2012-02401
• Study Type: interventional
• Target: 63
• Locations: 2 countries
• Sites: 41

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.

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

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (4)

• 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.)

• 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.)

• 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.)

• 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.

Study Arms (4)

Phase I: 75.25 Gy/36 fx + chemotherapy

EXPERIMENTAL

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.

Drug: carboplatin; Drug: paclitaxel; Radiation: three-dimensional conformal radiation therapy

Phase I: 74 Gy/37 fx + chemotherapy

EXPERIMENTAL

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.

Drug: carboplatin; Drug: paclitaxel; Radiation: three-dimensional conformal radiation therapy

Phase I: 70 Gy/35 fx + chemotherapy

EXPERIMENTAL

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.

Drug: carboplatin; Drug: paclitaxel; Radiation: three-dimensional conformal radiation therapy

Phase II: 74 Gy/37 fx + chemotherapy

EXPERIMENTAL

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.

Drug: carboplatin; Drug: paclitaxel; Radiation: three-dimensional conformal radiation therapy

Interventions

carboplatin DRUG

Phase I: 70 Gy/35 fx + chemotherapy; Phase I: 74 Gy/37 fx + chemotherapy; Phase I: 75.25 Gy/36 fx + chemotherapy; Phase II: 74 Gy/37 fx + chemotherapy

paclitaxel DRUG

Phase I: 70 Gy/35 fx + chemotherapy; Phase I: 74 Gy/37 fx + chemotherapy; Phase I: 75.25 Gy/36 fx + chemotherapy; Phase II: 74 Gy/37 fx + chemotherapy

three-dimensional conformal radiation therapy RADIATION

Phase I: 70 Gy/35 fx + chemotherapy; Phase I: 74 Gy/37 fx + chemotherapy; Phase I: 75.25 Gy/36 fx + chemotherapy; Phase II: 74 Gy/37 fx + chemotherapy

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Radiation Therapy Oncology Group: lead
• National Cancer Institute (NCI): collaborator

Study Sites (41)

Mobile Infirmary Medical Center

Mobile, Alabama, 36652-2144, United States

Location

Arizona Oncology Services Foundation

Phoenix, Arizona, 85013, United States

Location

Providence Saint Joseph Medical Center - Burbank

Burbank, California, 91505, United States

Location

Providence Holy Cross Cancer Center

Mission Hills, California, 91346-9600, United States

Location

University of California Davis Cancer Center

Sacramento, California, 95817, United States

Location

Bay Medical

Panama City, Florida, 32401, United States

Location

Northeast Georgia Medical Center

Gainesville, Georgia, 30501, United States

Location

Saint Anthony's Hospital at Saint Anthony's Health Center

Alton, Illinois, 62002, United States

Location

Alexian Brothers Radiation Oncology

Elk Grove Village, Illinois, 60007, United States

Location

Good Samaritan Regional Health Center

Mount Vernon, Illinois, 62864, United States

Location

Oncology Center at Saint Margaret Mercy Healthcare Center

Hammond, Indiana, 46320, United States

Location

Cancer Center at Ball Memorial Hospital

Muncie, Indiana, 47303-3499, United States

Location

Regional Cancer Center at Singing River Hospital

Pascagoula, Mississippi, 39581, United States

Location

Southeast Missouri Regional Cancer Center at Southeast Missouri Hospital

Cape Girardeau, Missouri, 63701, United States

Location

Cancer Institute of Cape Girardeau, LLC

Cape Girardeau, Missouri, 63703, United States

Location

Saint Francis Medical Center

Cape Girardeau, Missouri, 63703, United States

Location

CCOP - Cancer Research for the Ozarks

Springfield, Missouri, 65802, United States

Location

Hulston Cancer Center at Cox Medical Center South

Springfield, Missouri, 65807, United States

Location

CCOP - St. Louis-Cape Girardeau

St Louis, Missouri, 63141, United States

Location

David C. Pratt Cancer Center at St. John's Mercy

St Louis, Missouri, 63141, United States

Location

Ocean Medical Center at Meridian Health

Brick, New Jersey, 08724, United States

Location

J. Phillip Citta Regional Cancer Center at Community Medical Center

Toms River, New Jersey, 08755, United States

Location

Franklin & Edith Scarpa Regional Cancer Center at South Jersey Healthcare

Vineland, New Jersey, 08360, United States

Location

CCOP - Hematology-Oncology Associates of Central New York

East Syracuse, New York, 13057, United States

Location

High Point Regional Hospital

High Point, North Carolina, 27261, United States

Location

Summa Center for Cancer Care at Akron City Hospital

Akron, Ohio, 44309-2090, United States

Location

Cleveland Clinic Cancer Center at Fairview Hospital

Cleveland, Ohio, 44111, United States

Location

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, 44195, United States

Location

Cancer Treatment Center

Wooster, Ohio, 44691, United States

Location

Three Rivers Community Hospital

Grants Pass, Oregon, 97527, United States

Location

Dubs Cancer Center at Rogue Valley Medical Center

Medford, Oregon, 97504, United States

Location

Providence Cancer Center at PMCC

Medford, Oregon, 97504, United States

Location

Albert Einstein Cancer Center

Philadelphia, Pennsylvania, 19141, United States

Location

Rapid City Regional Hospital

Rapid City, South Dakota, 57701, United States

Location

University of Texas Medical Branch

Galveston, Texas, 77555-0361, United States

Location

Joe Arrington Cancer Research and Treatment Center

Lubbock, Texas, 79410-1894, United States

Location

Schiffler Cancer Center at Wheeling Hospital

Wheeling, West Virginia, 26003, United States

Location

Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center

La Crosse, Wisconsin, 54601, United States

Location

Medical College of Wisconsin Cancer Center

Milwaukee, Wisconsin, 53226, United States

Location

Veterans Affairs Medical Center - Milwaukee

Milwaukee, Wisconsin, 53295, United States

Location

Tom Baker Cancer Centre - Calgary

Calgary, Alberta, T2N 4N2, Canada

Location

Related 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 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.

  PMID: 20368547 RESULT

• 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.

  PMID: 20457350 RESULT

• 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.

  RESULT

MeSH Terms

Conditions

Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Adenocarcinoma of Lung

Interventions

Carboplatin; Paclitaxel

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Limitations and Caveats

This study was originally designed to escalate 3DRT via increasing doses per fraction. However, due to excessive toxicity at dose level 1 (75.25 Gy, 2.15 Gy/fraction), the protocol was amended in January 2003 to de-escalate 3DRT dose.

Results Point of Contact

• Title: Wendy Seiferheld
• Organization: Radiation Therapy Oncology Group

wseiferheld@acr.org

Study Officials

• Jeffrey Bradley, MD

  Mallinckrodt Institute of Radiology at Washington University Medical Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2001
• First Posted: April 9, 2003
• Study Start: July 1, 2001
• Primary Completion: January 1, 2009
• Study Completion: November 1, 2013
• Last Updated: December 22, 2017
• Results First Posted: March 27, 2014

Record last verified: 2017-11

Locations

US (40); CA (1)