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

Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00288054
• Other study ID #: CDR0000456381
• Secondary ID: U10CA032102S0429
• Status: Terminated
• Phase: Phase 1
• First received: February 6, 2006
• Last updated: January 2, 2013
• Start date: April 2006
• Est. completion date: April 2012

Study information

• Verified date: January 2013
• Source: Southwest Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 24
• Est. completion date: April 2012
• Est. primary completion date: April 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Cancer
• Lung Neoplasms

Intervention

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.

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.

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.

Locations

Country	Name	City	State
United States	McDowell Cancer Center at Akron General Medical Center	Akron	Ohio
United States	Alaska Regional Hospital Cancer Center	Anchorage	Alaska
United States	Hospital District Sixth of Harper County	Anthony	Kansas
United States	University of Colorado Cancer Center at UC Health Sciences Center	Aurora	Colorado
United States	Billings Clinic - Downtown	Billings	Montana
United States	CCOP - Montana Cancer Consortium	Billings	Montana
United States	Hematology-Oncology Centers of the Northern Rockies - Billings	Billings	Montana
United States	Northern Rockies Radiation Oncology Center	Billings	Montana
United States	St. Vincent Healthcare Cancer Care Services	Billings	Montana
United States	Eugene M. and Christine E. Lynn Cancer Institute at Boca Raton Community Hospital - Main Campus	Boca Raton	Florida
United States	Eugene M. and Christine E. Lynn Cancer Institute at Boca Raton Community Hospital - West	Boca Raton	Florida
United States	Boston University Cancer Research Center	Boston	Massachusetts
United States	Caritas St. Elizabeth's Medical Center	Brighton	Massachusetts
United States	St. James Healthcare Cancer Care	Butte	Montana
United States	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas
United States	Charles M. Barrett Cancer Center at University Hospital	Cincinnati	Ohio
United States	Cleveland Clinic Taussig Cancer Center	Cleveland	Ohio
United States	Danville Regional Medical Center	Danville	Virginia
United States	Veterans Affairs Medical Center - Denver	Denver	Colorado
United States	Barbara Ann Karmanos Cancer Institute	Detroit	Michigan
United States	Cancer Center of Kansas, PA - Dodge City	Dodge City	Kansas
United States	Shaw Regional Cancer Center	Edwards	Colorado
United States	Cancer Center of Kansas, PA - El Dorado	El Dorado	Kansas
United States	Poudre Valley Hospital	Fort Collins	Colorado
United States	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas
United States	Valley View Hospital Cancer Center	Glenwood Springs	Colorado
United States	Wayne Memorial Hospital, Incorporated	Goldsboro	North Carolina
United States	Big Sky Oncology	Great Falls	Montana
United States	Great Falls Clinic - Main Facility	Great Falls	Montana
United States	Sletten Cancer Institute at Benefis Healthcare	Great Falls	Montana
United States	Northern Montana Hospital	Havre	Montana
United States	St. Peter's Hospital	Helena	Montana
United States	Pardee Memorial Hospital	Hendersonville	North Carolina
United States	Cancer Center of Kansas-Independence	Independence	Kansas
United States	Glacier Oncology, PLLC	Kalispell	Montana
United States	Kalispell Medical Oncology at KRMC	Kalispell	Montana
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center	Kansas City	Kansas
United States	Good Samaritan Cancer Center at Good Samaritan Hospital	Kearney	Nebraska
United States	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Southwest Medical Center	Liberal	Kansas
United States	USC/Norris Comprehensive Cancer Center and Hospital	Los Angeles	California
United States	MedCentral - Mansfield Hospital	Mansfield	Ohio
United States	Tibotec Therapeutics - Division of Ortho Biotech Products, LP	Marysville	California
United States	Cardinal Bernardin Cancer Center at Loyola University Medical Center	Maywood	Illinois
United States	Tucker Center for Cancer Care at Orange Regional Medical Center	Middletown	New York
United States	Community Medical Center	Missoula	Montana
United States	Guardian Oncology and Center for Wellness	Missoula	Montana
United States	Montana Cancer Center at St. Patrick Hospital and Health Sciences Center	Missoula	Montana
United States	Montana Cancer Specialists at Montana Cancer Center	Missoula	Montana
United States	Montrose Memorial Hospital Cancer Center	Montrose	Colorado
United States	Ted B. Wahby Cancer Center at Mount Clemens General Hospital	Mount Clemens	Michigan
United States	Hematology Oncology Consultants - Naperville	Naperville	Illinois
United States	Cancer Center of Kansas, PA - Newton	Newton	Kansas
United States	Olathe Cancer Center	Olathe	Kansas
United States	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas
United States	Regional Cancer Center at Singing River Hospital	Pascagoula	Mississippi
United States	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas
United States	Highland Hospital of Rochester	Rochester	New York
United States	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York
United States	University of California Davis Cancer Center	Sacramento	California
United States	Cancer Center of Kansas, PA - Salina	Salina	Kansas
United States	Curtis and Elizabeth Anderson Cancer Institute at Memorial Health University Medical Center	Savannah	Georgia
United States	Providence Cancer Institute at Providence Hospital - Southfield Campus	Southfield	Michigan
United States	Iredell Memorial Hospital	Statesville	North Carolina
United States	Cotton-O'Neil Cancer Center	Topeka	Kansas
United States	Pearlman Comprehensive Cancer Center at South Georgia Medical Center	Valdosta	Georgia
United States	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas
United States	Associates in Womens Health, PA - North Review	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Medical Arts Tower	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Wichita	Wichita	Kansas
United States	CCOP - Wichita	Wichita	Kansas
United States	Via Christi Cancer Center at Via Christi Regional Medical Center	Wichita	Kansas
United States	Wesley Medical Center	Wichita	Kansas
United States	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas

Sponsors (2)

Lead Sponsor	Collaborator
Southwest Oncology Group	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Yes
Secondary	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.	Yes
Secondary	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.	No
Secondary	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.	No
Secondary	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	No