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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier:
NCT00023673
First received: September 13, 2001
Last updated: April 1, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Lung Cancer
Drug: carboplatin
Drug: paclitaxel
Radiation: three-dimensional conformal radiation therapy
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Radiation Therapy Oncology Group:

Primary Outcome Measures:
  • Maximum Tolerated Dose (MTD) of Three-dimensional Conformal Radiation Therapy (3DRT), in Terms of Gy Per Fraction, Combined With Concurrent Chemotherapy [ Time Frame: From start of treatment to 90 days ] [ Designated as safety issue: Yes ]

    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 RTOG (Radiation Therapy Oncolgy Group) 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


  • Percentage of Patients Who Survive at Least 12 Months [ Time Frame: From registration to 1 year ] [ Designated as safety issue: No ]
    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:
  • Toxicity [ Time Frame: From start of treatment to end of follow-up ] [ Designated as safety issue: Yes ]
  • Partial Organ Tolerance Doses for Lung and Esophagus [ Time Frame: From start of treatment to end of follow-up ] [ Designated as safety issue: Yes ]
  • Complete Response Rate at 3 Months After Therapy [ Time Frame: From start of treatment until 3 months after completion of therapy ] [ Designated as safety issue: No ]

Enrollment: 63
Study Start Date: July 2001
Study Completion Date: November 2013
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Phase I: 75.25 Gy/36 fx + chemotherapy
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
Experimental: Phase I: 74 Gy/37 fx + chemotherapy
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
Experimental: Phase I: 70 Gy/35 fx + chemotherapy
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
Experimental: Phase II: 74 Gy/37 fx + chemotherapy
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

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

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00023673

  Show 41 Study Locations
Sponsors and Collaborators
Radiation Therapy Oncology Group
Investigators
Study Chair: Jeffrey Bradley, MD Mallinckrodt Institute of Radiology at Washington University Medical Center
  More Information

Additional Information:
Publications:
Responsible Party: Radiation Therapy Oncology Group
ClinicalTrials.gov Identifier: NCT00023673     History of Changes
Other Study ID Numbers: RTOG L-0117, CDR0000068850, NCI-2012-02401
Study First Received: September 13, 2001
Results First Received: February 12, 2014
Last Updated: April 1, 2014
Health Authority: United States: Federal Government

Keywords provided by Radiation Therapy Oncology Group:
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

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carboplatin
Paclitaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 21, 2014