Gefitinib With or Without Carboplatin and Paclitaxel in Treating Older Patients With Unresectable or Metastatic Non-Small Cell Lung Cancer

Parallel Phase II Trials of ZD1839 (Iressa) Alone or Weekly Carboplatin and Paclitaxel Followed by ZD1839 (Iressa) (Oncologists Must Choose) for Metastatic Non-Small Cell Lung Cancer in Patients > or = 65 Years of Age

RATIONALE: Biological therapies such as gefitinib may interfere with the growth of cancer cells and slow the growth of the tumor. Drugs used in chemotherapy such as carboplatin and paclitaxel use different ways to stop tumor cells from dividing so they stop growing or die. Combining gefitinib with carboplatin and paclitaxel may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving gefitinib alone or together with carboplatin and paclitaxel works in treating older patients with unresectable or metastatic non-small cell lung cancer.

Study Overview

• Status: Completed
• Conditions: Lung Cancer
• Intervention / Treatment: Drug: carboplatin; Drug: paclitaxel; Drug: gefitinib

Detailed Description

OBJECTIVES:

Primary

• Determine the 6-month progression status of older patients with unresectable or metastatic non-small cell lung cancer treated with gefitinib alone or with carboplatin and paclitaxel.

Secondary

• Determine the response rate in patients treated with these regimens.
• Determine the quality of life of patients treated with these regimens.
• Determine whether serum-secreted or soluble epidermal growth factor receptor (EGFR) concentrations predict response in patients treated with these regimens.
• Correlate the presence of social support for these patients with toxicity and efficacy of these regimens.
• Determine whether social support for these patients differs according to gender.
• Determine the reasons an oncologist would choose a chemotherapy vs a nonchemotherapy regimen for these patients.

Tertiary

• Correlate EGFR signaling pathway markers, RNA expression profile, gene polymorphisms of prespecified germline and tumor genes, and plasma and urine proteomic patterns with response rate and time to progression of patients receiving treatment in group I.

OUTLINE: This is a nonrandomized, multicenter study. Patients are assigned to 1 of 2 treatment groups as determined by their treating physician.

• Group I: Patients receive oral gefitinib on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
• Group II: Patients receive paclitaxel IV over 1 hour and carboplatin IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. After completion of chemotherapy and in the absence of disease progression, patients receive oral gefitinib as in group I.

Quality of life is assessed at baseline and after the completion of course 2.

Patients are followed every 3 months for 5 years.

PROJECTED ACCRUAL: A total of 107 patients (51 for group I and 56 for group II) will be accrued for this study within 1.7 years.

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Saskatchewan
    • Regina, Saskatchewan, Canada, S4T 7T1
      • Allan Blair Cancer Centre at Pasqua Hospital
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Mayo Clinic Scottsdale
  • Colorado
    • Fort Collins, Colorado, United States, 80524
      • Front Range Cancer Specialists
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic - Jacksonville
  • Illinois
    • Aurora, Illinois, United States, 60507
      • Rush-Copley Cancer Care Center
    • Bloomington, Illinois, United States, 61701
      • St. Joseph Medical Center
    • Canton, Illinois, United States, 61520
      • Graham Hospital
    • Carthage, Illinois, United States, 62321
      • Memorial Hospital
    • Effingham, Illinois, United States, 62401
      • St. Anthony's Memorial Hospital
    • Eureka, Illinois, United States, 61530
      • Eureka Community Hospital
    • Galesburg, Illinois, United States, 61401
      • Galesburg Cottage Hospital
    • Galesburg, Illinois, United States, 61401
      • Galesburg Clinic
    • Havana, Illinois, United States, 62644
      • Mason District Hospital
    • Hopedale, Illinois, United States, 61747
      • Hopedale Medical Complex
    • Joliet, Illinois, United States, 60435
      • Joliet Oncology Hematology Associates, Limited - West
    • Kewanee, Illinois, United States, 61443
      • Kewanee Hospital
    • Macomb, Illinois, United States, 61455
      • Mcdonough District Hospital
    • Normal, Illinois, United States, 61761
      • Bromenn Regional Medical Center
    • Normal, Illinois, United States, 61761
      • Community Cancer Center
    • Ottawa, Illinois, United States, 61350
      • Community Hospital of Ottawa
    • Ottawa, Illinois, United States, 61350
      • Oncology Hematology Associates of Central Illinois - Ottawa
    • Pekin, Illinois, United States, 61554
      • Cancer Treatment Center at Pekin Hospital
    • Peoria, Illinois, United States, 61636
      • Methodist Medical Center of Illinois
    • Peoria, Illinois, United States, 61614
      • Proctor Hospital
    • Peoria, Illinois, United States, 61637
      • OSF St. Francis Medical Center
    • Peoria, Illinois, United States, 61615
      • CCOP - Illinois Oncology Research Association
    • Peoria, Illinois, United States, 61615
      • Oncology/Hematology Associates of Central Illinois, P.C.
    • Peru, Illinois, United States, 61354
      • Illinois Valley Community Hospital
    • Princeton, Illinois, United States, 61356
      • Perry Memorial Hospital
    • Spring Valley, Illinois, United States, 61362
      • St. Margaret's Hospital
    • Urbana, Illinois, United States, 61801
      • Carle Cancer Center at Carle Foundation Hospital
    • Urbana, Illinois, United States, 61801
      • CCOP - Carle Cancer Center
  • Indiana
    • Beech Grove, Indiana, United States, 46107
      • St. Francis Hospital and Health Centers - Beech Grove Campus
    • Michigan City, Indiana, United States, 46360
      • Saint Anthony Memorial Health Centers
  • Iowa
    • Cedar Rapids, Iowa, United States, 52402
      • St. Luke's Hospital
    • Cedar Rapids, Iowa, United States, 52403
      • Cedar Rapids Oncology Associates
    • Cedar Rapids, Iowa, United States, 52403
      • Mercy Regional Cancer Center at Mercy Medical Center
    • 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, 50307
      • Mercy Capitol Hospital
    • Des Moines, Iowa, United States, 50316-2301
      • John Stoddard Cancer Center at Iowa Lutheran Hospital
    • Sioux City, Iowa, United States, 51101
      • Siouxland Regional Cancer Center
    • Sioux City, Iowa, United States, 51104
      • St. Luke's Regional Medical Center
    • Sioux City, Iowa, United States, 51104
      • Mercy Medical Center - Sioux City
    • Sioux City, Iowa, United States, 51101
      • Siouxland Hematology-Oncology Associates at June E. Nylen Cancer Center
    • West Des Moines, Iowa, United States, 50266
      • Medical Oncology and Hematology Associates - West Des Moines
  • Kansas
    • Chanute, Kansas, United States, 66720
      • Cancer Center of Kansas, P.A. - Chanute
    • Dodge City, Kansas, United States, 67801
      • Cancer Center of Kansas, P.A. - Dodge City
    • El Dorado, Kansas, United States, 67042
      • Cancer Center of Kansas, P.A. - El Dorado
    • Kingman, Kansas, United States, 67068
      • Cancer Center of Kansas, P.A. - Kingman
    • Liberal, Kansas, United States, 67901
      • Southwest Medical Center
    • Newton, Kansas, United States, 67114
      • Cancer Center of Kansas, P.A. - Newton
    • Parsons, Kansas, United States, 67357
      • Cancer Center of Kansas, P.A. - Parsons
    • Pratt, Kansas, United States, 67124
      • Cancer Center of Kansas, P.A. - Pratt
    • Salina, Kansas, United States, 67042
      • Cancer Center of Kansas, P.A. - Salina
    • Wellington, Kansas, United States, 67152
      • Cancer Center of Kansas, P.A. - Wellington
    • Wichita, Kansas, United States, 67214
      • CCOP - Wichita
    • Wichita, Kansas, United States, 67214
      • Via Christi Cancer Center at Via Christi Regional Medical Center
    • Wichita, Kansas, United States, 67214
      • Cancer Center of Kansas, P.A. - Wichita
    • Wichita, Kansas, United States, 67203
      • Associates in Womens Health, P.A. - North Review
    • Wichita, Kansas, United States, 67208
      • Cancer Center of Kansas, P.A. - Medical Arts Tower
    • Winfield, Kansas, United States, 67156
      • Cancer Center of Kansas, P.A. - Winfield
  • 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, P.C.
    • Monroe, Michigan, United States, 48162
      • Community Cancer Center of Monroe
    • Monroe, Michigan, United States, 48162
      • Mercy Memorial Hospital System
  • Minnesota
    • Alexandria, Minnesota, United States, 56308
    • Bemidji, Minnesota, United States, 56601
      • MeritCare Clinic - Bemidji
    • Brainerd, Minnesota, United States, 56401
      • Brainerd Medical Center
    • Brainerd, Minnesota, United States, 56401
      • St. Joseph's Medical Center
    • Burnsville, Minnesota, United States, 55337
      • Fairview Ridges Hospital
    • Coon Rapids, Minnesota, United States, 55433
      • Mercy and Unity Cancer Center at Mercy Hospital
    • Edina, Minnesota, United States, 55435
      • Fairview Southdale Hospital
    • Fergus Falls, Minnesota, United States, 56537
    • Fridley, Minnesota, United States, 55432
      • Mercy and Unity Cancer Center at Unity Hospital
    • Hutchinson, Minnesota, United States, 55350
      • Hutchinson Area Health Care
    • Lichfield, Minnesota, United States, 55355
      • Meeker County Memorial Hospital
    • Maplewood, Minnesota, United States, 55109
      • St. John's Hospital
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center - Minneapolis
    • Minneapolis, Minnesota, United States, 55407
      • Virginia Piper Cancer Institute at Abbott-Northwestern Hospital
    • Montevideo, Minnesota, United States, 56265
      • Chippewa County - Montevideo Hospital
    • Robbinsdale, Minnesota, United States, 55422-2900
      • Hubert H. Humphrey Cancer Center at North Memorial Medical Center
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Cancer Center
    • Saint Cloud, Minnesota, United States, 56303
      • Coborn Cancer Center
    • Saint Louis Park, Minnesota, United States, 55416
      • CCOP - Metro-Minnesota
    • Shakopee, Minnesota, United States, 55379
      • Saint Francis Cancer Center
    • St Paul, Minnesota, United States, 55102
      • St. Joseph's Hospital
    • St. Cloud, Minnesota, United States, 56303
      • CentraCare Clinic - River Campus
    • St. Louis Park, Minnesota, United States, 55416
      • Park Nicollet Health Services
    • St. Paul, Minnesota, United States, 55102
      • United Hospital
    • St. Paul, Minnesota, United States, 55101
      • Regions Hospital Cancer Care Center
    • Waconia, Minnesota, United States, 55387
      • Ridgeview Medical Center
    • Woodbury, Minnesota, United States, 55125
      • Woodwinds Health Campus
  • North Dakota
    • Bismarck, North Dakota, United States, 58501
      • Bismarck Cancer Center
    • Bismarck, North Dakota, United States, 58501
      • Cancer Care Center at Medcenter One Hospital
    • Bismarck, North Dakota, United States, 58501
      • Mid Dakota Clinic, P. C.
    • Bismarck, North Dakota, United States, 58502
      • St. Alexius Medical Center
    • Fargo, North Dakota, United States, 58122
      • CCOP - MeritCare Hospital
    • Fargo, North Dakota, United States, 58122
      • MeritCare Medical Group
    • Grand Forks, North Dakota, United States, 58201
      • Altru Cancer Center at Altru Hospital
  • Ohio
    • Bowling Green, Ohio, United States, 43402
      • Wood County Oncology Center
    • Dayton, Ohio, United States, 45428
      • Veterans Affairs Medical Center - Dayton
    • Dayton, Ohio, United States, 45405
      • Grandview Hospital
    • Dayton, Ohio, United States, 45406
      • Good Samaritan Hospital
    • Dayton, Ohio, United States, 45409
      • David L. Rike Cancer Center at Miami Valley Hospital
    • Dayton, Ohio, United States, 45415
      • Samaritan North Cancer Care Center
    • Dayton, Ohio, United States, 45429
      • CCOP - Dayton
    • Findlay, Ohio, United States, 45840
      • Blanchard Valley Medical Associates
    • Fremont, Ohio, United States, 43420
      • Fremont Memorial Hospital
    • Kenton, Ohio, United States, 43326
      • Kenton Oncology, Incorporated
    • Kettering, Ohio, United States, 45429
      • Charles F. Kettering 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
    • Middletown, Ohio, United States, 45044
      • Middletown Regional 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
      • Promedica Cancer Center at Flower Hospital
    • 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, 43623
      • Toledo Clinic, Incorporated - Main Clinic
    • Toledo, Ohio, United States, 43623
      • CCOP - Toledo Community Hospital
    • Toledo, Ohio, United States, 43614
      • Medical College of Ohio Cancer Institute
    • Toledo, Ohio, United States, 43623
      • Toledo Surgical Specialists
    • Troy, Ohio, United States, 45373-1300
      • UVMC Cancer Care Center at Upper Valley Medical Center
    • Wauseon, Ohio, United States, 43567
      • Fulton County Health Center
    • Xenia, Ohio, United States, 45385
      • Ruth G. McMillan Cancer Center at Greene Memorial Hospital
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18105
      • Morgan Cancer Center at Lehigh Valley Hospital - Cedar Crest
    • Danville, Pennsylvania, United States, 17822-0001
      • Geisinger Medical Center
    • State College, Pennsylvania, United States, 16801
      • Geisinger Medical Group
    • Wilkes-Barre, Pennsylvania, United States, 18711
      • Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57117-5039
      • Sioux Valley Hospital and University of South Dakota Medical Center
    • Sioux Falls, South Dakota, United States, 57105-1080
      • Avera McKennan Hospital and University Health Center
    • Sioux Falls, South Dakota, United States, 57105
      • Medical X-Ray Center, P. C.
  • Wisconsin
    • La Crosse, Wisconsin, United States, 54601
      • Franciscan Skemp Healthcare

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years to 120 years (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

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

  • Metastatic or unresectable disease

• Measurable disease

  • At least 1 lesion at least 2.0 cm
  • Disease must be completely outside prior radiotherapy port OR documented disease progression since the completion of radiotherapy
• No meningeal carcinomatosis

• No untreated brain metastases

  • Current metastatic CNS disease must have been treated and clinically stable for at least 2 weeks prior to study chemotherapy
• No potentially curative treatment options available (e.g., chemotherapy with surgery or radiotherapy)

PATIENT CHARACTERISTICS:

Age

• 65 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 12 weeks

Hematopoietic

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Hemoglobin at least 10.0 g/dL

Hepatic

• Bilirubin no greater than 2.0 mg/dL
• No uncontrolled hepatic disease

Renal

• Creatinine no greater than 2 times upper limit of normal
• No uncontrolled renal disease

Cardiovascular

• No uncontrolled cardiac disease

Pulmonary

• No clinically active interstitial lung disease

  • Asymptomatic, chronic stable radiographic changes allowed
• No uncontrolled respiratory disease

Other

• Fertile patients must use effective contraception
• Able and willing to complete questionnaires alone or with assistance
• No known hypersensitivity to gefitinib or any of its excipients
• No active infection within the past 2 weeks
• No other prior malignancy within the past 5 years except basal cell skin cancer
• No grade 2 or greater peripheral neuropathy (CTC v2.0)
• No uncontrolled diabetes mellitus (for patients receiving study chemotherapy)
• No dysphagia or inability to swallow intact capsules
• No significant medical condition that would preclude study treatment or follow-up
• No severe or uncontrolled systemic disease

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics
• No prior chemotherapy for metastatic NSCLC

Endocrine therapy

• Concurrent steroids allowed provided the dose is not changed

Radiotherapy

• See Disease Characteristics
• At least 3 weeks since prior radiotherapy and recovered
• No prior radiotherapy to more than 25% of marrow-containing skeleton
• No concurrent radiotherapy (including palliative)

Surgery

• See Disease Characteristics
• At least 3 weeks since prior major surgery
• No surgery within 7 days after study participation

Other

• More than 30 days since prior non-FDA approved investigational drugs
• No concurrent oral retinoids

• No concurrent CYP3A4-inducing agents, including the following:

  • Carbamazepine
  • Oxcarbazepine
  • Modafinil
  • Ethosuximide
  • Griseofulvin
  • Nafcillin
  • Phenobarbital
  • Phenylbutazone
  • Phenytoin
  • Primidone
  • Rifampin
  • Hypericum perforatum (St. John's wort)
  • Barbiturates
  • Sulfinpyrazone
• No concurrent drugs that cause sustained elevation of gastric pH (≥ 5)
• No concurrent antacids within 4 hours before, during, and within 4 hours after gefitinib administration
• No concurrent itraconazole, fluconazole, ketoconazole, or erythromycin

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: gefitinib; Patients receive oral gefitinib on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline and after the completion of course 2. Patients are followed every 3 months for 5 years.	Drug: gefitinib
Experimental: paclitaxel + carboplatin + gefitinib; Patients receive paclitaxel IV over 1 hour and carboplatin IV over 30 minutes on days 1, 8, and 15. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. After completion of chemotherapy and in the absence of disease progression, patients receive oral gefitinib as in group I. Quality of life is assessed at baseline and after the completion of course 2. Patients are followed every 3 months for 5 years.	Drug: carboplatin; Drug: paclitaxel; Drug: gefitinib

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression status at 6 months	at 6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Progression-free survival	Up to 5 years
Overall survival	Up to 5 years
Confirmed response rate (complete or partial response)	Up to 5 years
Quality of life as assessed by the Lung Cancer Symptom scale	Up to 5 years
Social support measure as assessed by the Lubben Social Network scale	Up to 5 years

Collaborators and Investigators

• Sponsor: Alliance for Clinical Trials in Oncology
• Collaborators: National Cancer Institute (NCI)

Publications and helpful links

General Publications

• Mc Kean H, Stella PJ, Hillman SL, Rowland KM, Cannon MW, Behrens RJ, Gross GG, Sborov MD, Friedman EL, Jatoi A. Exploring therapeutic decisions in elderly patients with non-small cell lung cancer: results and conclusions from North Central Cancer Treatment Group Study N0222. Cancer Invest. 2011 May;29(4):266-71. doi: 10.3109/07357907.2010.535061. Epub 2011 Feb 23.

Study record dates

Study Major Dates

• Study Start: October 1, 2004
• Primary Completion (Actual): August 1, 2006
• Study Completion (Actual): November 1, 2010

Study Registration Dates

• First Submitted: June 5, 2003
• First Submitted That Met QC Criteria: June 5, 2003
• First Posted (Estimate): June 6, 2003

Study Record Updates

• Last Update Posted (Estimate): December 14, 2016
• Last Update Submitted That Met QC Criteria: December 12, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: stage IIIB non-small cell lung cancer; stage IV 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; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Protein Kinase Inhibitors; Carboplatin; Paclitaxel; Gefitinib
• Other Study ID Numbers: NCCTG-N0222; NCI-2012-02535 (Registry Identifier: CTRP (Clinical Trials Reporting System)); CDR0000304453 (Registry Identifier: PDQ (Physician Data Query))