S0429: Docetaxel, Cetuximab, and Radiation Therapy in Treating Patients With Stage III Non-Small Cell Lung Cancer

A Pilot (Phase I) Study of Weekly Docetaxel and Cetuximab Chemoradiation for Poor Risk Stage III Non-Small Cell Lung Cancer

RATIONALE: Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as cetuximab, can block tumor growth in different ways. Some find tumor cells and kill them or carry tumor-killing substances to them. Others interfere with the ability of tumor cells to grow and spread. Radiation therapy uses high-energy x-rays to kill tumor cells. Giving docetaxel and cetuximab together with radiation therapy may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of docetaxel when given together with cetuximab and radiation therapy in treating patients with stage III non-small cell lung cancer.

Study Overview

• Status: Terminated
• Conditions: Lung Cancer
• Intervention / Treatment: Biological: cetuximab; Radiation: radiation therapy; Drug: docetaxel

Detailed Description

OBJECTIVES:

Primary

• Test the feasibility and toxicity of combined cetuximab, weekly docetaxel, and concurrent radiotherapy in patients with poor-risk stage III non-small cell lung cancer (NSCLC).

Secondary

• Evaluate response rates (confirmed and unconfirmed, complete and partial) as well as overall and progression-free survival.
• Correlate EGFR mutations, KRAS mutations, EGFR/HER2 gene copy number detected by FISH, and protein expression by immunohistochemistry of EGFR-HER signaling pathways, phosphorylation, proliferative markers, apoptotic markers, selected oncogene markers, and markers for angiogenesis in biopsied pre-treatment tumor tissues with response and survival outcomes.
• Explore possible associations between changes in plasma angiogenic factors (VEGF, IL-8, bFGF) and cytokine levels (IL-6, IL-1α, ICAM, TGF-β, and others) and the risk of treatment-related pneumonitis and esophagitis.

OUTLINE: Patients are enrolled sequentially to 1 of 2 treatment groups.

• Cohort 1: Patients receive cetuximab IV over 1-2 hours on days 1, 8, 15, and 22.
• Cohort 2: Patients receive cetuximab as in group 1 followed by docetaxel IV over 15-30 minutes on days 8, 15, and 22 of course 1 and on days 1, 8, 15, and 22 of course 2.

Initially, 27 patients will be enrolled in Cohort 1. Once all patients in Cohort 1 have discontinued treatment, if toxicity rates are acceptable per protocol specifications, an additional 27 patients will be enrolled to Cohort 2. Treatment in both cohorts repeats every 28 days for 2 courses in the absence of disease progression or unacceptable toxicity. All patients also undergo radiotherapy once daily, 5 days a week, beginning on day 8 of course 1 and continuing through course 2 (approximately 7 weeks). Patients with no progressive disease then receive cetuximab alone once weekly. Treatment with cetuximab alone continues in the absence of disease progression for up to 2 years.

After completion of study treatment, patients are followed periodically for up to 3 years.

PROJECTED ACCRUAL: A total of 54 patients will be accrued for this study.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Alaska
    • Anchorage, Alaska, United States, 99508
      • Alaska Regional Hospital Cancer Center
  • California
    • Los Angeles, California, United States, 90089-9181
      • USC/Norris Comprehensive Cancer Center and Hospital
    • Marysville, California, United States, 95901
      • Tibotec Therapeutics - Division of Ortho Biotech Products, LP
    • Sacramento, California, United States, 95817
      • University of California Davis Cancer Center
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Cancer Center at UC Health Sciences Center
    • Denver, Colorado, United States, 80220
      • Veterans Affairs Medical Center - Denver
    • Edwards, Colorado, United States, 81632
      • Shaw Regional Cancer Center
    • Fort Collins, Colorado, United States, 80524
      • Poudre Valley Hospital
    • Glenwood Springs, Colorado, United States, 81601
      • Valley View Hospital Cancer Center
    • Montrose, Colorado, United States, 81401
      • Montrose Memorial Hospital Cancer Center
  • Florida
    • Boca Raton, Florida, United States, 33428
      • Eugene M. and Christine E. Lynn Cancer Institute at Boca Raton Community Hospital - West
    • Boca Raton, Florida, United States, 33486
      • Eugene M. and Christine E. Lynn Cancer Institute at Boca Raton Community Hospital - Main Campus
  • Georgia
    • Savannah, Georgia, United States, 31403-3089
      • Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center
    • Valdosta, Georgia, United States, 31603
      • Pearlman Comprehensive Cancer Center at South Georgia Medical Center
  • Illinois
    • Maywood, Illinois, United States, 60153
      • Cardinal Bernardin Cancer Center at Loyola University Medical Center
    • Naperville, Illinois, United States, 60540
      • Hematology Oncology Consultants - Naperville
  • Kansas
    • Anthony, Kansas, United States, 67003
      • Hospital District Sixth of Harper County
    • Chanute, Kansas, United States, 66720
      • Cancer Center of Kansas, PA - Chanute
    • Dodge City, Kansas, United States, 67801
      • Cancer Center of Kansas, PA - Dodge City
    • El Dorado, Kansas, United States, 67042
      • Cancer Center of Kansas, PA - El Dorado
    • Fort Scott, Kansas, United States, 66701
      • Cancer Center of Kansas - Fort Scott
    • Independence, Kansas, United States, 67301
      • Cancer Center of Kansas-Independence
    • Kansas City, Kansas, United States, 66160-7357
      • Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
    • Kingman, Kansas, United States, 67068
      • Cancer Center of Kansas, PA - Kingman
    • Lawrence, Kansas, United States, 66044
      • Lawrence Memorial Hospital
    • Liberal, Kansas, United States, 67901
      • Southwest Medical Center
    • Newton, Kansas, United States, 67114
      • Cancer Center of Kansas, PA - Newton
    • Olathe, Kansas, United States, 66061
      • Olathe Cancer Center
    • Parsons, Kansas, United States, 67357
      • Cancer Center of Kansas, PA - Parsons
    • Pratt, Kansas, United States, 67124
      • Cancer Center of Kansas, PA - Pratt
    • Salina, Kansas, United States, 67042
      • Cancer Center of Kansas, PA - Salina
    • Topeka, Kansas, United States, 66606
      • Cotton-O'Neil Cancer Center
    • Wellington, Kansas, United States, 67152
      • Cancer Center of Kansas, PA - Wellington
    • Wichita, Kansas, United States, 67214
      • Wesley Medical Center
    • Wichita, Kansas, United States, 67208
      • Cancer Center of Kansas, PA - Medical Arts Tower
    • Wichita, Kansas, United States, 67214
      • Cancer Center of Kansas, PA - Wichita
    • 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, 67208
      • Associates in Womens Health, PA - North Review
    • Winfield, Kansas, United States, 67156
      • Cancer Center of Kansas, PA - Winfield
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston University Cancer Research Center
    • Brighton, Massachusetts, United States, 02135-2997
      • Caritas St. Elizabeth's Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48201-1379
      • Barbara Ann Karmanos Cancer Institute
    • Mount Clemens, Michigan, United States, 48043
      • Ted B. Wahby Cancer Center at Mount Clemens General Hospital
    • Southfield, Michigan, United States, 48075
      • Providence Cancer Institute at Providence Hospital - Southfield Campus
  • Mississippi
    • Pascagoula, Mississippi, United States, 39581
      • Regional Cancer Center at Singing River Hospital
  • Montana
    • Billings, Montana, United States, 59101
      • CCOP - Montana Cancer Consortium
    • Billings, Montana, United States, 59101
      • Hematology-Oncology Centers of the Northern Rockies - Billings
    • Billings, Montana, United States, 59101
      • Northern Rockies Radiation Oncology Center
    • Billings, Montana, United States, 59101
      • St. Vincent Healthcare Cancer Care Services
    • Billings, Montana, United States, 59107-7000
      • Billings Clinic - Downtown
    • Butte, Montana, United States, 59701
      • St. James Healthcare Cancer Care
    • Great Falls, Montana, United States, 59405
      • Great Falls Clinic - Main Facility
    • Great Falls, Montana, United States, 59405
    • Great Falls, Montana, United States, 59405-5309
      • Big Sky Oncology
    • Great Falls, Montana, United States, 59405
      • Sletten Cancer Institute at Benefis Healthcare
    • Havre, Montana, United States, 59501
      • Northern Montana Hospital
    • Helena, Montana, United States, 59601
      • St. Peter's Hospital
    • Kalispell, Montana, United States, 59901
      • Kalispell Regional Medical Center
    • Kalispell, Montana, United States, 59901
      • Glacier Oncology, PLLC
    • Kalispell, Montana, United States, 59901
      • Kalispell Medical Oncology at KRMC
    • Missoula, Montana, United States, 59801
      • Community Medical Center
    • Missoula, Montana, United States, 59804
      • Guardian Oncology and Center for Wellness
    • Missoula, Montana, United States, 59807-7877
      • Montana Cancer Specialists at Montana Cancer Center
    • Missoula, Montana, United States, 59807
      • Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
  • Nebraska
    • Kearney, Nebraska, United States, 68848-1990
      • Good Samaritan Cancer Center at Good Samaritan Hospital
  • New York
    • Middletown, New York, United States, 10940-4199
      • Tucker Center for Cancer Care at Orange Regional Medical Center
    • Rochester, New York, United States, 14642
      • James P. Wilmot Cancer Center at University of Rochester Medical Center
    • Rochester, New York, United States, 14620
      • Highland Hospital of Rochester
  • North Carolina
    • Goldsboro, North Carolina, United States, 27534
      • Wayne Memorial Hospital, Incorporated
    • Hendersonville, North Carolina, United States, 28791
      • Pardee Memorial Hospital
    • Statesville, North Carolina, United States, 28677
      • Iredell Memorial Hospital
  • Ohio
    • Akron, Ohio, United States, 44307
      • McDowell Cancer Center at Akron General Medical Center
    • Cincinnati, Ohio, United States, 45267
      • Charles M. Barrett Cancer Center at University Hospital
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Taussig Cancer Center
    • Mansfield, Ohio, United States, 44903
      • MedCentral - Mansfield Hospital
  • Virginia
    • Danville, Virginia, United States, 24541
      • Danville Regional Medical Center

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 proven newly diagnosed single, primary, bronchogenic stage IIIA or selected stage IIIB (excluding malignant pleural effusion) non-small cell lung cancer (NSCLC) of one of the following cellular types:

  • Adenocarcinoma
  • Large cell carcinoma
  • Squamous cell carcinoma
  • Unspecified
• Histology or cytology from involved mediastinal or supraclavicular nodes will be sufficient for diagnosis if a separate primary lesion of the lung parenchyma is clearly evident on radiographs (i.e., a second biopsy will not be required)

• Underwent positron emission tomography (PET) scan within the past 42 days

  • N2 or N3 mediastinal disease by PET scan OR enlarged nodes on CT scan determined to be N2 or N3 by biopsy

• Measurable disease, defined as lesions that can be accurately measured in at least one dimension as ≥ 2 cm by conventional techniques or ≥ 1 cm by spiral CT scan

  • Pleural effusion, ascites, bone lesions, and laboratory parameters are not considered measurable disease
• No brain metastases

• Malignant pleural effusion allowed provided 1 of the following is true:

  • Present before mediastinoscopy or exploratory thoracotomy AND the pleural fluid is transudate with negative cytology
  • Present only after but not before exploratory or staging thoracotomy AND the pleural fluid is either transudate or exudate with negative cytology
  • Present only on CT scan but not on decubitus chest x-ray AND deemed too small to tap under either CT scan or ultrasound guidance

PATIENT CHARACTERISTICS:

• Zubrod performance status 0-1, meeting ≥ 1 of the following criteria OR Zubrod performance status 2 with no co-morbidities or meeting 1 of the following criteria:

  • No co-morbidities
  • FEV_1 < 2 L OR < 1 L with estimated contralateral FEV_1 ≥ 0.6 L
  • DLCO > 10 mL/mm Hg/min
  • Albumin < 0.85 times lower limit of normal
  • Unintentional weight loss > 10% within the past 6 months
  • Controlled congestive heart failure which, in the opinion of the investigator, may become decompensated due to radiotherapy
• FEV_1 < 2 L OR < 1 L with estimated contralateral FEV_1 ≥ 0.6 L
• Absolute neutrophil count ≥ 1,500/mm^3
• Platelet count ≥ 100,000/mm^3
• Serum creatinine ≤ 1.5 times upper limit of normal (ULN)
• Must provide prior smoking history
• Serum bilirubin normal

• Meets one of the following criteria:

  • Alkaline phosphatase (AP) ≤ 4 times ULN AND SGOT or SGPT normal
  • AP normal AND SGOT or SGPT ≤ 2.5 times ULN
• No other prior malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or adequately treated stage I or II cancer from which the patient is currently in complete remission
• No pregnant or nursing patients
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

• No prior chemotherapy or curative surgery for this cancer
• No prior radiotherapy to the neck and/or thorax for any reason
• No prior therapy which specifically targets the EGFR pathway
• No concurrent growth factors (e.g., filgrastim [G-CSF], epoetin alfa, or pegfilgrastim) or amifostine
• No concurrent intensity-modulated radiotherapy
• No concurrent prophylactic mediastinal, contralateral hilar, or supraclavicular lymph node radiotherapy

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cetuximab + Radiotherapy (no Docetaxel)	Biological: cetuximab; Cohorts 1 and 2: 400 mg/m2 (initial dose) 2 hour IV infusion on Day 1, Cycle 1 only. 250 mg/m2, 1 hour IV infusion on Days 8 , 15 and 22 during Cycle 1. 250 mg/m2 (subsequent doses), 1 hour IV infusion on Days 1, 8 , 15 and 22 during subsequent cycles.; Radiation: radiation therapy; Radiation therapy should begin on Day 8 of Cycle 1 and continue through the end of Cycle 2. Refer to Section 12.1 for Radiation Therapy Review. RT prescription should be PTV (GTV + 2-cm margins on CT scan) to 6,480 cGy in 36 fractions given 5 days a week, 180 cGy per day. The dose is prescribed to the isocenter. The entire treatment should be planned prior to starting treatment to ensure that the plan meets protocol specifications.
Experimental: Cetuximab + Radiotherapy + Docetaxel	Biological: cetuximab; Cohorts 1 and 2: 400 mg/m2 (initial dose) 2 hour IV infusion on Day 1, Cycle 1 only. 250 mg/m2, 1 hour IV infusion on Days 8 , 15 and 22 during Cycle 1. 250 mg/m2 (subsequent doses), 1 hour IV infusion on Days 1, 8 , 15 and 22 during subsequent cycles.; Radiation: radiation therapy; Radiation therapy should begin on Day 8 of Cycle 1 and continue through the end of Cycle 2. Refer to Section 12.1 for Radiation Therapy Review. RT prescription should be PTV (GTV + 2-cm margins on CT scan) to 6,480 cGy in 36 fractions given 5 days a week, 180 cGy per day. The dose is prescribed to the isocenter. The entire treatment should be planned prior to starting treatment to ensure that the plan meets protocol specifications.; Drug: docetaxel; Cohort 2 ONLY: 20 mg/m2 IV over 15 - 30 minutes on Days 8, 15 and 22 of Cycle 1. Concurrent with RT and cetuximab starting at Week 2. 20 mg/m2 IV over 15 - 30 minutes on Days 1, 8, 15 and 22 of Cycle 2.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment-related Esophagitis or Pneumonitis	The primary endpoint will be the rate of Grade 3 or greater esophagitis and/or pneumonitis within 4 months after discontinuation of radiation therapy.	Weekly for the first 8 weeks, then every 4 weeks thereafter for up to 4 months after complettion of radiotherapy.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Toxicity	Only adverse events that are possibly, probably or definitely related to study drug are reported.	Weekly for the first 8 weeks, then every 4 weeks while subject on protocol treatment.
Overall Survival	The duration form the date of enrollment until the date of death due to any cause. Patients last known to be alive are censored at the date of last contact.	weekly while patient is on protocol treatment, then monthly thereafter.
Progression-free Survival.	Duration from the date of enrollment until the date of progression (as defined by RECIST: >= 20% increase over baseline in the sum of longest diameters, or appearance of new lesions, or non-measurable disease that is clearly worsening in the opinion of the treating investigator, or symptomatic deterioration) or death due to any cause. Patients last known to be alive and free of disease progression are censored at the date of last contact.	At week 10, week 22, and then every 3 months until progression for up to 3 years after enrollment.
Response Rate	Confirmed and unconfirmed complete and partial responses in the subset of patients with measurable disease (as defined per RECIST). A confirmed complete response (CR) is defined as disappearance of all disease, confirmed by a second determination of CR at least 4 weeks later. A confirmed partial response (PR) is defined as a >= 30% decrease from baseline in the sum of longest diameters, confirmed by a second determination of PR at least 4 weeks later. A patient is considered to have measurable disease if they have at least one lesion with a longest diameter of >= 2 cm by conventional CT, or >= 1 cm by spiral CT.	Week 10 and week 22

Collaborators and Investigators

• Sponsor: Southwest Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Derick H. Lau, MD, University of California, Davis; Principal Investigator: Yuhchyau Chen, MD, PhD, James P. Wilmot Cancer Center; Principal Investigator: Kishan J. Pandya, MD, James P. Wilmot Cancer Center; Principal Investigator: Karen Kelly, MD, University of Colorado, Denver; Principal Investigator: Laurie E. Gaspar, MD, MBA, University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start: April 1, 2006
• Primary Completion (Actual): April 1, 2012
• Study Completion (Actual): April 1, 2012

Study Registration Dates

• First Submitted: February 6, 2006
• First Submitted That Met QC Criteria: February 6, 2006
• First Posted (Estimate): February 7, 2006

Study Record Updates

• Last Update Posted (Estimate): January 4, 2013
• Last Update Submitted That Met QC Criteria: January 2, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Keywords: stage IIIA non-small cell lung cancer; stage IIIB non-small cell lung cancer; squamous cell lung cancer; large cell lung cancer; adenocarcinoma of the lung
• 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, Immunological; Docetaxel; Cetuximab
• Other Study ID Numbers: CDR0000456381; U10CA032102 (U.S. NIH Grant/Contract); S0429 (Other Identifier: SWOG)