Combination Chemotherapy Plus Radiation Therapy in Treating Patients With Non-Small Cell Lung Cancer

Phase I/II Study Of Concurrent Chemotherapy And Escalating Doses Of Radiotherapy (RT) For Unresectable Non-Small Cell Lung Cancer (NSCLC) Using A New RT Paradigm

RATIONALE: Drugs used in chemotherapy use 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 chemotherapy and radiation therapy may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of radiation therapy when given with combination chemotherapy and to see how well they work in treating patients with non-small cell lung cancer that cannot be surgically removed.

Study Overview

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

Detailed Description

OBJECTIVES:

• Determine the maximum tolerated dose of radiotherapy in combination with carboplatin and paclitaxel in patients with unresectable non-small cell lung cancer.
• Determine the 2-year survival of patients treated with this regimen.
• Determine the progression-free local control rate in patients treated this regimen.
• Determine the tolerability of this regimen in these patients.
• Assess the quality of life of patients treated with this regimen.

OUTLINE: This is a multicenter, dose-escalation study of radiotherapy.

Patients undergo radiotherapy* once daily 5 days a week for 7 weeks and 2 days (a total of 37 fractions). Patients concurrently receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes once weekly for 7 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity.

NOTE: *No prophylactic nodal radiotherapy is administered

Cohorts of 3-6 patients receive escalating doses of radiotherapy until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, 12 additional patients are treated at that dose level in the phase II portion of the study.

Beginning 3 weeks after completion of radiotherapy, patients receive paclitaxel and carboplatin as above. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity.

Quality of life is assessed at baseline, once during the last week of radiotherapy, and then every 3 months for 2 years.

Patients are followed at 3 weeks, every 3 months for 21 months, and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 90 patients will be accrued for this study.

• Study Type: Interventional
• Enrollment (Actual): 69
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259-5499
      • Mayo Clinic Scottsdale
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic - Jacksonville
  • Iowa
    • Ames, Iowa, United States, 50010
      • McFarland Clinic, PC
    • Des Moines, Iowa, United States, 50309
      • CCOP - Iowa Oncology Research Association
    • Des Moines, Iowa, United States, 50309
      • John Stoddard Cancer Center at Iowa Methodist Medical Center
    • Des Moines, Iowa, United States, 50309
      • Medical Oncology and Hematology Associates at John Stoddard Cancer Center
    • Des Moines, Iowa, United States, 50314
      • Medical Oncology and Hematology Associates at Mercy Cancer Center
    • Des Moines, Iowa, United States, 50314
      • Mercy Cancer Center at Mercy Medical Center - Des Moines
    • Des Moines, Iowa, United States, 50316
      • John Stoddard Cancer Center at Iowa Lutheran Hospital
    • Des Moines, Iowa, United States, 50307
      • Mercy Capitol Hospital
    • Sioux City, Iowa, United States, 51101
      • Siouxland Hematology-Oncology Associates, LLP
    • Sioux City, Iowa, United States, 51104
      • St. Luke's Regional Medical Center
    • Sioux City, Iowa, United States, 51104
      • Mercy Medical Center - Sioux City
  • Michigan
    • Adrian, Michigan, United States, 49221
      • Hickman Cancer Center at Bixby Medical Center
    • Lambertville, Michigan, United States, 48144
      • Haematology-Oncology Associates of Ohio and Michigan, PC
    • Monroe, Michigan, United States, 48162
      • Community Cancer Center of Monroe
    • Monroe, Michigan, United States, 48162
      • Mercy Memorial Hospital - Monroe
  • Minnesota
    • Bemidji, Minnesota, United States, 56601
      • MeritCare Bemidji
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Cancer Center
  • Nebraska
    • Omaha, Nebraska, United States, 68106
      • CCOP - Missouri Valley Cancer Consortium
    • Omaha, Nebraska, United States, 68122
      • Immanuel Medical Center
    • Omaha, Nebraska, United States, 68124
      • Alegant Health Cancer Center at Bergan Mercy Medical Center
    • Omaha, Nebraska, United States, 68131-2197
      • Creighton University Medical Center
  • North Dakota
    • Bismarck, North Dakota, United States, 58501
      • Bismarck Cancer Center
    • Bismarck, North Dakota, United States, 58501
      • Medcenter One Hospital Cancer Care Center
    • Bismarck, North Dakota, United States, 58501
      • Mid Dakota Clinic, PC
    • Bismarck, North Dakota, United States, 58502
      • St. Alexius Medical Center Cancer Center
    • Fargo, North Dakota, United States, 58122
      • CCOP - MeritCare Hospital
    • Fargo, North Dakota, United States, 58122
      • MeritCare Broadway
  • Ohio
    • Bowling Green, Ohio, United States, 43402
      • Wood County Oncology Center
    • Fremont, Ohio, United States, 43420
      • Fremont Memorial Hospital
    • Lima, Ohio, United States, 45804
      • Lima Memorial Hospital
    • Maumee, Ohio, United States, 43537
      • Northwest Ohio Oncology Center
    • Maumee, Ohio, United States, 43537
      • St. Luke's Hospital
    • Oregon, Ohio, United States, 43616
      • St. Charles Mercy Hospital
    • Oregon, Ohio, United States, 43616
      • Toledo Clinic - Oregon
    • Sandusky, Ohio, United States, 44870
      • Firelands Regional Medical Center
    • Sandusky, Ohio, United States, 44870
      • North Coast Cancer Care, Incorporated
    • Sylvania, Ohio, United States, 43560
      • Flower Hospital Cancer Center
    • Tiffin, Ohio, United States, 44883
      • Mercy Hospital of Tiffin
    • Toledo, Ohio, United States, 43608
      • St. Vincent Mercy Medical Center
    • Toledo, Ohio, United States, 43606
      • Toledo Hospital
    • Toledo, Ohio, United States, 43614
      • Medical University of Ohio Cancer Center
    • Toledo, Ohio, United States, 43617
      • CCOP - Toledo Community Hospital
    • Toledo, Ohio, United States, 43623
      • Toledo Clinic, Incorporated - Main Clinic
    • Wauseon, Ohio, United States, 43567
      • Fulton County Health Center
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Avera Cancer Institute
    • Sioux Falls, South Dakota, United States, 57105
      • Medical X-Ray Center, PC
    • Sioux Falls, South Dakota, United States, 57117-5039
      • Sanford Cancer Center at Sanford USD Medical Center
  • Virginia
    • Fredericksburg, Virginia, United States, 22401
      • Fredericksburg Oncology, Incorporated
  • Wisconsin
    • La Crosse, Wisconsin, United States, 54601
      • Franciscan Skemp Healthcare - La Crosse Campus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed non-small cell lung cancer (NSCLC)

  • Stage I, II, or III NSCLC that is unresectable due to tumor extent or other medical reasons
• Measurable disease
• Tumor must not exceed volume that would require radiation volumes greater than those allowed on this study
• No more than blunting of the costophrenic angle on chest x-ray due to pleural effusions
• No more than small effusions seen on chest CT scan only
• No supraclavicular adenopathy

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• ECOG 0-1

Life expectancy:

• At least 12 weeks

Hematopoietic:

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic:

• Total bilirubin no greater than 1.5 times upper limit of normal (ULN) OR
• Direct bilirubin no greater than 1.5 times ULN
• AST no greater than 3 times ULN

Renal:

• Creatinine clearance at least 40 mL/min

Cardiovascular:

• No New York Heart Association class III or IV heart disease

Pulmonary:

• FEV_1 at least 1 L or 35% of predicted

Other:

• No grade 2 or greater peripheral neuropathy
• No weight loss of 10% or more within the past 3 months
• No uncontrolled infection
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, adequately treated noninvasive carcinoma (carcinoma in situ), or localized prostate cancer
• No other severe underlying disease that would preclude study participation
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic:

• No prior biologic therapy for NSCLC
• No concurrent biologic therapy
• No concurrent prophylactic filgrastim (G-CSF)

Chemotherapy:

• No prior chemotherapy for NSCLC
• No other concurrent chemotherapy

Endocrine therapy:

• No prior endocrine therapy for NSCLC

Radiotherapy:

• No prior radiotherapy for NSCLC

Surgery:

• No prior surgery for NSCLC

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: radiotherapy + paclitaxel + carboplatin; Patients undergo radiotherapy once daily 5 days a week for 7 weeks and 2 days (a total of 37 fractions). Patients concurrently receive paclitaxel IV over 3 hours and carboplatin IV over 30 minutes once weekly for 7 weeks. Treatment continues in the absence of disease progression or unacceptable toxicity. Beginning 3 weeks after completion of radiotherapy, patients receive paclitaxel and carboplatin as above. Treatment repeats every 21 days for 3 courses in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline, once during the last week of radiotherapy, and then every 3 months for 2 years. Patients are followed at 3 weeks, every 3 months for 21 months, and then every 6 months for 3 years.

Drug: carboplatin; Radiation: radiation therapy; Drug: paclitaxel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum tolerated dose (MTD) as assessed by dose-limiting toxicity within 1 month after completion of study treatment (phase I)	Up to 1 month
Survival at 2 years (phase II)	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to progression	Up to 5 years
Survival time	Up to 5 years
Toxicity	Up to 5 years
Time to local progression	Up to 5 years

Collaborators and Investigators

• Sponsor: Alliance for Clinical Trials in Oncology
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Steven E. Schild, MD, Mayo Clinic

Publications and helpful links

General Publications

• Schild S, Graham D, Hillman S, et al.: Survival of patients (pts) treated with high-dose radiotherapy (RT) and concurrent chemotherapy for unresectable non-small cell lung cancer (NSCLC). [Abstract] J Clin Oncol 27 (Suppl 15): A-7544, 2009.
• Schild SE, McGinnis WL, Graham D, Hillman S, Fitch TR, Northfelt D, Garces YI, Shahidi H, Tschetter LK, Schaefer PL, Adjei A, Jett J. Results of a Phase I trial of concurrent chemotherapy and escalating doses of radiation for unresectable non-small-cell lung cancer. Int J Radiat Oncol Biol Phys. 2006 Jul 15;65(4):1106-11. doi: 10.1016/j.ijrobp.2006.02.046. Epub 2006 May 26.
• Schild SE, Hillman SL, Tan AD, Ross HJ, McGinnis WL, Garces YA, Graham DL, Adjei AA, Jett JR; Mayo Clinic, North Central Cancer Treatment Group. Long-Term Results of a Trial of Concurrent Chemotherapy and Escalating Doses of Radiation for Unresectable Non-Small Cell Lung Cancer: NCCTG N0028 (Alliance). J Thorac Oncol. 2017 Apr;12(4):697-703. doi: 10.1016/j.jtho.2016.12.021. Epub 2017 Jan 12.

Study record dates

Study Major Dates

• Study Start: May 1, 2002
• Primary Completion (Actual): January 1, 2008
• Study Completion (Actual): January 1, 2010

Study Registration Dates

• First Submitted: March 8, 2002
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): December 1, 2016
• Last Update Submitted That Met QC Criteria: November 30, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: stage IIIA non-small cell lung cancer; stage IIIB non-small cell lung cancer; stage I non-small cell lung cancer; stage II 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; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Carboplatin; Paclitaxel
• Other Study ID Numbers: NCCTG-N0028; NCI-2012-02458 (Registry Identifier: CTRP (Clinical Trials Reporting System)); CDR0000069250 (Registry Identifier: PDQ (Physician Data Query))