Clinical trial NCT00288054: S0429: Docetaxel, Cetuximab, and Radiation Therapy in Treating Patients With Stage III Non-Small Cell Lung Cancer
Official title: A Pilot (Phase I) Study of Weekly Docetaxel and Cetuximab Chemoradiation for Poor Risk Stage III Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Lung Cancer
Keywords: stage IIIA non-small cell lung cancer
stage IIIB non-small cell lung cancer
adenocarcinoma of the lung
large cell lung cancer
squamous cell lung cancer
Lead sponsor: SWOG Cancer Research Network
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2006-02-07
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Treatment-related Esophagitis or Pneumonitis
timeFrame: Weekly for the first 8 weeks, then every 4 weeks thereafter for up to 4 months after complettion of radiotherapy.
Secondary outcomes:
measure: Toxicity
timeFrame: Weekly for the first 8 weeks, then every 4 weeks while subject on protocol treatment.
measure: Overall Survival
timeFrame: weekly while patient is on protocol treatment, then monthly thereafter.
measure: Progression-free Survival.
timeFrame: At week 10, week 22, and then every 3 months until progression for up to 3 years after enrollment.
measure: Response Rate
timeFrame: Week 10 and week 22
Other outcomes:
Locations:
city: Anchorage
country: United States
facility: Alaska Regional Hospital Cancer Center
state: Alaska
city: Los Angeles
country: United States
facility: USC/Norris Comprehensive Cancer Center and Hospital
state: California
city: Marysville
country: United States
facility: Tibotec Therapeutics - Division of Ortho Biotech Products, LP
state: California
city: Sacramento
country: United States
facility: University of California Davis Cancer Center
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center at UC Health Sciences Center
state: Colorado
city: Denver
country: United States
facility: Veterans Affairs Medical Center - Denver
state: Colorado
city: Edwards
country: United States
facility: Shaw Regional Cancer Center
state: Colorado
city: Fort Collins
country: United States
facility: Poudre Valley Hospital
state: Colorado
city: Glenwood Springs
country: United States
facility: Valley View Hospital Cancer Center
state: Colorado
city: Montrose
country: United States
facility: Montrose Memorial Hospital Cancer Center
state: Colorado
city: Boca Raton
country: United States
facility: Eugene M. and Christine E. Lynn Cancer Institute at Boca Raton Community Hospital - West
state: Florida
city: Boca Raton
country: United States
facility: Eugene M. and Christine E. Lynn Cancer Institute at Boca Raton Community Hospital - Main Campus
state: Florida
city: Savannah
country: United States
facility: Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center
state: Georgia
city: Valdosta
country: United States
facility: Pearlman Comprehensive Cancer Center at South Georgia Medical Center
state: Georgia
city: Maywood
country: United States
facility: Cardinal Bernardin Cancer Center at Loyola University Medical Center
state: Illinois
city: Naperville
country: United States
facility: Hematology Oncology Consultants - Naperville
state: Illinois
city: Anthony
country: United States
facility: Hospital District Sixth of Harper County
state: Kansas
city: Chanute
country: United States
facility: Cancer Center of Kansas, PA - Chanute
state: Kansas
city: Dodge City
country: United States
facility: Cancer Center of Kansas, PA - Dodge City
state: Kansas
city: El Dorado
country: United States
facility: Cancer Center of Kansas, PA - El Dorado
state: Kansas
city: Fort Scott
country: United States
facility: Cancer Center of Kansas - Fort Scott
state: Kansas
city: Independence
country: United States
facility: Cancer Center of Kansas-Independence
state: Kansas
city: Kansas City
country: United States
facility: Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center
state: Kansas
city: Kingman
country: United States
facility: Cancer Center of Kansas, PA - Kingman
state: Kansas
city: Lawrence
country: United States
facility: Lawrence Memorial Hospital
state: Kansas
city: Liberal
country: United States
facility: Southwest Medical Center
state: Kansas
city: Newton
country: United States
facility: Cancer Center of Kansas, PA - Newton
state: Kansas
city: Olathe
country: United States
facility: Olathe Cancer Center
state: Kansas
city: Parsons
country: United States
facility: Cancer Center of Kansas, PA - Parsons
state: Kansas
city: Pratt
country: United States
facility: Cancer Center of Kansas, PA - Pratt
state: Kansas
city: Salina
country: United States
facility: Cancer Center of Kansas, PA - Salina
state: Kansas
city: Topeka
country: United States
facility: Cotton-O'Neil Cancer Center
state: Kansas
city: Wellington
country: United States
facility: Cancer Center of Kansas, PA - Wellington
state: Kansas
city: Wichita
country: United States
facility: Associates in Womens Health, PA - North Review
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas, PA - Medical Arts Tower
state: Kansas
city: Wichita
country: United States
facility: Cancer Center of Kansas, PA - Wichita
state: Kansas
city: Wichita
country: United States
facility: CCOP - Wichita
state: Kansas
city: Wichita
country: United States
facility: Via Christi Cancer Center at Via Christi Regional Medical Center
state: Kansas
city: Wichita
country: United States
facility: Wesley Medical Center
state: Kansas
city: Winfield
country: United States
facility: Cancer Center of Kansas, PA - Winfield
state: Kansas
city: Boston
country: United States
facility: Boston University Cancer Research Center
state: Massachusetts
city: Brighton
country: United States
facility: Caritas St. Elizabeth's Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Mount Clemens
country: United States
facility: Ted B. Wahby Cancer Center at Mount Clemens General Hospital
state: Michigan
city: Southfield
country: United States
facility: Providence Cancer Institute at Providence Hospital - Southfield Campus
state: Michigan
city: Pascagoula
country: United States
facility: Regional Cancer Center at Singing River Hospital
state: Mississippi
city: Billings
country: United States
facility: CCOP - Montana Cancer Consortium
state: Montana
city: Billings
country: United States
facility: Hematology-Oncology Centers of the Northern Rockies - Billings
state: Montana
city: Billings
country: United States
facility: Northern Rockies Radiation Oncology Center
state: Montana
city: Billings
country: United States
facility: St. Vincent Healthcare Cancer Care Services
state: Montana
city: Billings
country: United States
facility: Billings Clinic - Downtown
state: Montana
city: Butte
country: United States
facility: St. James Healthcare Cancer Care
state: Montana
city: Great Falls
country: United States
facility: Big Sky Oncology
state: Montana
city: Great Falls
country: United States
facility: Great Falls Clinic - Main Facility
state: Montana
city: Great Falls
country: United States
facility: Sletten Cancer Institute at Benefis Healthcare
state: Montana
city: Great Falls
country: United States
state: Montana
city: Havre
country: United States
facility: Northern Montana Hospital
state: Montana
city: Helena
country: United States
facility: St. Peter's Hospital
state: Montana
city: Kalispell
country: United States
facility: Glacier Oncology, PLLC
state: Montana
city: Kalispell
country: United States
facility: Kalispell Medical Oncology at KRMC
state: Montana
city: Kalispell
country: United States
facility: Kalispell Regional Medical Center
state: Montana
city: Missoula
country: United States
facility: Community Medical Center
state: Montana
city: Missoula
country: United States
facility: Guardian Oncology and Center for Wellness
state: Montana
city: Missoula
country: United States
facility: Montana Cancer Specialists at Montana Cancer Center
state: Montana
city: Missoula
country: United States
facility: Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
state: Montana
city: Kearney
country: United States
facility: Good Samaritan Cancer Center at Good Samaritan Hospital
state: Nebraska
city: Middletown
country: United States
facility: Tucker Center for Cancer Care at Orange Regional Medical Center
state: New York
city: Rochester
country: United States
facility: Highland Hospital of Rochester
state: New York
city: Rochester
country: United States
facility: James P. Wilmot Cancer Center at University of Rochester Medical Center
state: New York
city: Goldsboro
country: United States
facility: Wayne Memorial Hospital, Incorporated
state: North Carolina
city: Hendersonville
country: United States
facility: Pardee Memorial Hospital
state: North Carolina
city: Statesville
country: United States
facility: Iredell Memorial Hospital
state: North Carolina
city: Akron
country: United States
facility: McDowell Cancer Center at Akron General Medical Center
state: Ohio
city: Cincinnati
country: United States
facility: Charles M. Barrett Cancer Center at University Hospital
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
city: Mansfield
country: United States
facility: MedCentral - Mansfield Hospital
state: Ohio
city: Danville
country: United States
facility: Danville Regional Medical Center
state: Virginia
Study officials:
affiliation: James P. Wilmot Cancer Center
name: Yuhchyau Chen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: James P. Wilmot Cancer Center
name: Kishan J. Pandya, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, Davis
name: Derick H. Lau, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Colorado, Denver
name: Karen Kelly, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Colorado, Denver
name: Laurie E. Gaspar, MD, MBA
role: PRINCIPAL_INVESTIGATOR
References: