Gemcitabine, Carboplatin or Paclitaxel Plus Radiation Therapy in Treating Patients With Stage IIIA or IIIB Non-Small Cell Lung Cancer

A Phase I Study of Gemcitabine, Carboplatin or Gemcitabine, Paclitaxel and Radiation Therapy Followed by Adjuvant Chemotherapy for Patients With Favorable Prognosis Inoperable Stage IIIA/B Non-Small Cell Lung Cancer (NSCLC)

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

PURPOSE: Phase I trial to study the effectiveness of combining combination chemotherapy with radiation therapy in treating patients who have stage IIIA or stage IIIB non-small cell lung cancer.

Study Overview

• Status: Completed
• Conditions: Lung Cancer
• Intervention / Treatment: Drug: carboplatin; Radiation: radiation therapy; Drug: gemcitabine hydrochloride; Drug: paclitaxel

Detailed Description

OBJECTIVES:

• Determine the maximum tolerated dose (MTD) of gemcitabine when administered with carboplatin and thoracic radiotherapy followed by adjuvant gemcitabine and carboplatin in patients with stage IIIA or IIIB non-small cell lung cancer.
• Determine the MTD of gemcitabine and paclitaxel when administered with thoracic radiotherapy followed by adjuvant gemcitabine and carboplatin in these patients.

OUTLINE: This is a multicenter, dose-escalation study of gemcitabine and paclitaxel. Patients are sequentially assigned to 1 of 3 treatment regimens.

• Regimen A: Patients receive gemcitabine IV over 30-60 minutes on days 1, 8, 22, 29, and 43 and thoracic radiotherapy daily 5 days a week for 7 weeks beginning on day 1.
• Regimen B (closed to accrual as of 5/13/03): Patients receive gemcitabine and thoracic radiotherapy as in regimen A and carboplatin IV over 30 minutes on days 1, 8, 22, 29, and 43.
• Regimen C: Patients receive gemcitabine and thoracic radiotherapy as in regimen A and paclitaxel IV over 1 hour on days 1, 8, 22, 29, and 43.

At 3 weeks after completion of chemoradiotherapy, all patients receive adjuvant gemcitabine IV over 30-60 minutes on days 71, 78, 92, and 99 and carboplatin IV over 30 minutes on days 71 and 92.

The first 6 patients enrolled receive regimen A to determine the safety of the initial dose of gemcitabine. After completion of regimen A, cohorts of 3-6 patients receive escalating doses of gemcitabine in regimen B (closed to accrual as of 5/13/03) until the maximum tolerated dose (MTD) is determined. In a separate sequence, cohorts of 3-6 patients receive alternating escalating doses of gemcitabine and paclitaxel in regimen C until the MTD is determined. The MTD is defined as the dose preceding that at which at least 3 of 6 patients experience dose-limiting toxicity.

Patients are followed at 3 months, 6 months, every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

PROJECTED ACCRUAL: A maximum of 78 patients will be accrued for this study within 29 months.

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Oakland, California, United States, 94609-3305
      • CCOP - Bay Area Tumor Institute
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Sylvester Comprehensive Cancer Center
  • Iowa
    • Dubuque, Iowa, United States, 52001
      • Wendt Regional Cancer Center of Finley Hospital
  • New Jersey
    • Long Branch, New Jersey, United States, 07740-6395
      • Monmouth Medical Center
  • Ohio
    • Akron, Ohio, United States, 44304
      • Akron City Hospital
    • Salem, Ohio, United States, 44460
      • Cancer Care Center, Incorporated
  • Pennsylvania
    • Drexel Hill, Pennsylvania, United States, 19026
      • Delaware County Memorial Hospital
    • East Stroudsburg, Pennsylvania, United States, 18301
      • Dale and Frances Hughes Cancer Center
    • Pittsburgh, Pennsylvania, United States, 15219
      • Mercy Hospital of Pittsburgh
  • Tennessee
    • Nashville, Tennessee, United States, 37232-5671
      • Vanderbilt-Ingram Cancer Center at Vanderbilt Medical Center
  • Utah
    • Murray, Utah, United States, 84107
      • Cottonwood Hospital Medical Center
    • Ogden, Utah, United States, 84403
      • McKay-Dee Hospital Center
    • Provo, Utah, United States, 84604
      • Utah Valley Regional Medical Center - Provo
    • Saint George, Utah, United States, 84770
      • Dixie Regional Medical Center
    • Salt Lake City, Utah, United States, 84143
      • LDS Hospital
  • Virginia
    • Danville, Virginia, United States, 24541
      • Danville Regional Medical Center
  • Wisconsin
    • La Crosse, Wisconsin, United States, 54601
      • Gundersen Lutheran Cancer Center at Gundersen Lutheran Medical Center
    • Milwaukee, Wisconsin, United States, 53295
      • Veterans Affairs Medical Center - Milwaukee (Zablocki)
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed loco-regionally advanced non-small cell lung cancer meeting one of the following staging criteria:

  • Medically inoperable stage IIIA
  • Unresectable stage IIIA or IIIB
• Measurable disease on three-dimensional planning CT scan
• No post-resection intrathoracic tumor recurrence
• No pleural effusion on chest x-ray except those occurring after attempted thoracotomy or other invasive thoracic procedure
• No evidence of small cell histology
• No evidence of hematogenous or distant metastases

PATIENT CHARACTERISTICS:

Age:

• Not specified

Performance status:

• Zubrod 0-1

Life expectancy:

• Not specified

Hematopoietic:

• Platelet count at least 100,000/mm^3
• Absolute granulocyte count at least 2,000/mm^3
• Hemoglobin at least 8.0 g/dL

Hepatic:

• Bilirubin no greater than 1.5 mg/dL
• Serum glutamate oxaloacetate transaminase (SGOT) no greater than 1.5 times upper limit of normal (unless caused by documented benign disease)

Renal:

• Creatinine no greater than 1.5 mg/dL

Cardiovascular:

• No myocardial infarction within the past 6 months
• No symptomatic heart disease, including angina, congestive heart failure, or uncontrolled arrhythmia

Pulmonary:

• Forced expiratory volume (FEV)_1 greater than 1,000 mL

Other:

• No other invasive malignancy within the past 3 years except nonmelanoma skin cancer
• No weight loss of more than 10% in 3 months prior to diagnosis
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• Not specified

Chemotherapy:

• No prior chemotherapy

Endocrine therapy:

• Not specified

Radiotherapy:

• No prior thoracic or neck radiotherapy

Surgery:

• See Disease Characteristics
• No prior complete or subtotal tumor resection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

13

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; Sequence A: Gemcitabine 300 mg/m2/week plus radiation therapy (RT)	Radiation: radiation therapy; Drug: gemcitabine hydrochloride
Experimental: Arm 2; Sequence B: Gemcitabine 300 mg/m2/week plus paclitaxel 30 mg/m2/week and RT	Radiation: radiation therapy; Drug: gemcitabine hydrochloride; Drug: paclitaxel
Experimental: Arm 3; Sequence A: Gemcitabine 300 mg/m2/week plus carboplatin 2 AUC and RT	Drug: carboplatin; Radiation: radiation therapy; Drug: gemcitabine hydrochloride
Experimental: Arm 4; Sequence B: Gemcitabine 450 mg/m2/week plus paclitaxel 30 mg/m2/week and RT	Radiation: radiation therapy; Drug: gemcitabine hydrochloride; Drug: paclitaxel
Experimental: Arm 6; Sequence B: Gemcitabine 450 mg/m2/week plus paclitaxel 40 mg/m2/week and RT	Radiation: radiation therapy; Drug: gemcitabine hydrochloride; Drug: paclitaxel
Experimental: Arm 8; Sequence B: Gemcitabine 600 mg/m2/week plus paclitaxel 40 mg/m2/week and RT	Radiation: radiation therapy; Drug: gemcitabine hydrochloride; Drug: paclitaxel
Experimental: Arm 10; Sequence B: Gemcitabine 600 mg/m2/week plus paclitaxel 50 mg/m2/week and RT	Radiation: radiation therapy; Drug: gemcitabine hydrochloride; Drug: paclitaxel
Experimental: Arm 12; Sequence B: Gemcitabine 750 mg/m2/week plus paclitaxel 50 mg/m2/week and RT	Radiation: radiation therapy; Drug: gemcitabine hydrochloride; Drug: paclitaxel
Experimental: Arm 14; Sequence B: Gemcitabine 900 mg/m2/week plus paclitaxel 50 mg/m2/week and RT	Radiation: radiation therapy; Drug: gemcitabine hydrochloride; Drug: paclitaxel
Experimental: Arm 5; Sequence A: Gemcitabine 450 mg/m2/week plus carboplatin 2 AUC and RT	Drug: carboplatin; Radiation: radiation therapy; Drug: gemcitabine hydrochloride
Experimental: Arm 7; Sequence A: Gemcitabine 600 mg/m2/week plus carboplatin 2 AUC and RT	Drug: carboplatin; Radiation: radiation therapy; Drug: gemcitabine hydrochloride
Experimental: Arm 9; Sequence A: Gemcitabine 750 mg/m2/week plus carboplatin 2 AUC and RT	Drug: carboplatin; Radiation: radiation therapy; Drug: gemcitabine hydrochloride
Experimental: Arm 11; Sequence A: Gemcitabine 900 mg/m2/week plus carboplatin 2 AUC and RT	Drug: carboplatin; Radiation: radiation therapy; Drug: gemcitabine hydrochloride

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To determine the maximum tolerated dose of gemcitabine with carboplatin-based chemotherapy and radiation therapy	From start of treatment to 90 days
To determine the maximum tolerated dose of gemcitabine with paclitaxel-based chemotherapy and radiation therapy	From start of treatment to 90 days

Collaborators and Investigators

• Sponsor: Radiation Therapy Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Hak Choy, MD, Simmons Cancer Center

Publications and helpful links

General Publications

• Choy H, Jain AK, Moughan J, Curran W, Whipple G, Demas WF, Ettinger DS. RTOG 0017: a phase I trial of concurrent gemcitabine/carboplatin or gemcitabine/paclitaxel and radiation therapy ("ping-pong trial") followed by adjuvant chemotherapy for patients with favorable prognosis inoperable stage IIIA/B non-small cell lung cancer. J Thorac Oncol. 2009 Jan;4(1):80-6. doi: 10.1097/JTO.0b013e318191503f.
• Choy H, Swann S, Curran W, et al.: A phase I trial of gemcitabine, carboplatin or gemcitabine, paclitaxel and concurrent radiation therapy followed by consolidative gemcitabine and carboplatin for inoperable stage III non-small cell lung cancer: an RTOG 0017 study. [Abstract] Int J Radiat Oncol Biol Phys 63 (2 Suppl 1): A-70, S42, 2005.
• Choy H, Swann S, Walter C, et al.: A phase I trial of gemcitabine, carboplatin or gemcitabine, paclitaxel and concurrent radiation therapy followed by consolidative gemcitabine and carboplatin for inoperable stage III non-small cell lung cancer: an RTOG study. [Abstract] J Clin Oncol 23 (Suppl 16): A-7103, 646s, 2005.

Study record dates

Study Major Dates

• Study Start: May 1, 2001
• Primary Completion (Actual): January 1, 2009
• Study Completion (Actual): June 1, 2010

Study Registration Dates

• First Submitted: May 6, 2001
• First Submitted That Met QC Criteria: May 6, 2003
• First Posted (Estimate): May 7, 2003

Study Record Updates

• Last Update Posted (Estimate): November 17, 2015
• Last Update Submitted That Met QC Criteria: November 14, 2015
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Keywords: stage IIIA non-small cell lung cancer; stage IIIB non-small cell lung cancer
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Gemcitabine; Carboplatin; Paclitaxel
• Other Study ID Numbers: RTOG-0017; RTOG-L-0017; CDR0000068622