S0636: Erlotinib and Bevacizumab in Never-Smokers With Stage IIIB or Stage IV Primary Non-Small Cell Lung Cancer

Lung Cancer Clinical Trial

Official title:

A Phase II Trial of the Combination of OSI-774 (Erlotinib; NSC-718781) and Bevacizumab (RHUMAB VEGF; NSC 704865) in Never-Smokers With Stage IIIB and IV Primary NSCLC Adenocarcinomas

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00445848
• Other study ID #: CDR0000531056
• Secondary ID: S0636U10CA032102
• Status: Completed
• Phase: Phase 2
• Start date: July 2007
• Est. completion date: January 2014

Study information

• Verified date: February 2020
• Source: Southwest Oncology Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab also may stop the growth of non-small cell lung cancer by blocking blood flow to the tumor. Giving erlotinib together with bevacizumab may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving erlotinib together with bevacizumab works in treating patients with stage IIIB or stage IV primary non-small cell lung cancer who have never smoked.

Description:

OBJECTIVES:

Primary

• Assess overall survival of patients with stage IIIB or IV primary non-small cell lung adenocarcinoma who have never smoked and are treated with erlotinib hydrochloride and bevacizumab.

Secondary

• Assess progression-free survival of patients treated with this regimen.

• Assess the response rate (confirmed and unconfirmed, complete and partial) in a subset of patients with measurable disease treated with this regimen.

• Evaluate the frequency and severity of toxicities associated with this regimen in these patients.

OUTLINE: This is a multicenter study.

Patients receive oral erlotinib hydrochloride daily on days 1-21 and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

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

PROJECTED ACCRUAL: A total of 80 patients will be accrued for this study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 89
• Est. completion date: January 2014
• Est. primary completion date: August 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

DISEASE CHARACTERISTICS:

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

• Adenocarcinoma

• No component of squamous cell carcinoma present

• Incompletely resected or unresectable disease

• Stage IIIB or IV disease as defined below:

• Selected stage IIIB disease

• T4 (cytologically confirmed malignant pleural effusion OR pleural tumor foci that are separate from direct pleural invasion by the primary tumor)

• Any N

• M0

• Stage IV disease

• Any T

• Any N

• M1 (distant metastases present)

• Recurrent lung cancer in a separate lobe after resection or radiotherapy within the past 5 years OR multifocal lesions in > 1 lobe considered stage IV disease

• New lesions occurring = 5 years after resection may be considered a separate primary cancer and are not allowed if this is the only focus of lung cancer

• Measurable and/or nonmeasurable disease by CT scan, positron emission tomography scan, or MRI

• Disease must be present outside a previous radiotherapy field OR a new lesion must be inside the port

• Measurable disease must be assessed within the past 28 days

• Nonmeasurable disease must be assessed within the past 42 days

• Pleural effusions, ascites, and laboratory parameters are not acceptable as the only evidence of disease

• Must be a lifelong nonsmoker (< 100 cigarettes in lifetime)

• Treated brain metastases allowed provided the patient is asymptomatic and do not require steroids

PATIENT CHARACTERISTICS:

• Zubrod performance status 0-2

• Absolute neutrophil count = 1,500/mm^3

• Platelet count = 100,000/mm^3

• Total bilirubin normal

• SGOT or SGPT = 2.5 times upper limit of normal (ULN) (5 times ULN if liver metastases present)

• Alkaline phosphatase = 2.5 times ULN (5 times ULN if bone metastases present)

• Creatinine = 1.5 times ULN OR creatinine clearance = 50 mL/min

• Urine protein:creatinine ratio = 0.5 OR urine protein < 1,000 mg by 24-hour urine collection

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• Hypertension allowed if controlled on medication prior to study enrollment

• Must be willing to provide prior smoking history

• No immediate life-threatening complications from malignancies

• No prior major medical condition, psychological condition, or social situation that would preclude study treatment

• No hemoptysis = ½ teaspoon within the past 28 days

• No clinical history of pulmonary or upper respiratory hemorrhage = grade 2 within the past 6 months or grade 1 within the past 28 days

• No history of either thrombosis or hemorrhage, including hemorrhagic or thrombotic stroke, or other CNS bleeding

• No serious nonhealing wound, ulcer, or bone fracture

• No other prior malignancy except for the following:

• Adequately treated basal cell or squamous cell skin cancer

• Adequately treated stage I or II cancer from which the patient is currently in complete remission

• In situ cervical cancer

• Any other cancer from which the patient has been disease-free for 5 years

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics

• At least 7 days since prior fine-needle aspiration or core biopsy

• At least 28 days since prior radiotherapy (14 days for palliative radiotherapy) and recovered

• At least 28 days since prior surgery (e.g., thoracic or other major surgeries) and recovered

• At least 28 days since prior systemic chemotherapy

• Prior biologic therapy allowed

• No prior gefitinib, erlotinib hydrochloride, bevacizumab, or other targeted therapies against the epidermal growth factor receptor or vascular endothelial growth factor axes

• Concurrent stable, therapeutic anticoagulation therapy allowed (e.g., warfarin or low molecular weight heparin), provided the patient has no history of bleeding complications on anticoagulation or an inability to establish a stable therapeutic regimen for anticoagulation

• No concurrent surgery

• No other concurrent nonprotocol treatment (including chemotherapy, hormonal therapy, biological therapy, or radiotherapy) directed at this cancer

Related Conditions & MeSH terms

• Lung Cancer
• Lung Neoplasms

Intervention

Biological:
• bevacizumab

Drug:
• erlotinib hydrochloride

Locations

Country	Name	City	State
United States	CCOP - Michigan Cancer Research Consortium	Ann Arbor	Michigan
United States	Saint Joseph Mercy Cancer Center	Ann Arbor	Michigan
United States	Kaiser Permanente - Deer Valley	Antioch	California
United States	Randolph Hospital	Asheboro	North Carolina
United States	CCOP - Atlanta Regional	Atlanta	Georgia
United States	Northside Hospital Cancer Center	Atlanta	Georgia
United States	Piedmont Hospital	Atlanta	Georgia
United States	Saint Joseph's Hospital of Atlanta	Atlanta	Georgia
United States	University of Colorado Cancer Center at UC Health Sciences Center	Aurora	Colorado
United States	WellStar Cobb Hospital	Austell	Georgia
United States	Battle Creek Health System Cancer Care Center	Battle Creek	Michigan
United States	St. Joseph Cancer Center	Bellingham	Washington
United States	Alta Bates Summit Comprehensive Cancer Center	Berkeley	California
United States	Mecosta County Medical Center	Big Rapids	Michigan
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	Boston University Cancer Research Center	Boston	Massachusetts
United States	Bozeman Deaconess Cancer Center	Bozeman	Montana
United States	Olympic Hematology and Oncology	Bremerton	Washington
United States	Peninsula Medical Center	Burlingame	California
United States	St. James Healthcare Cancer Care	Butte	Montana
United States	Rocky Mountain Oncology	Casper	Wyoming
United States	Cancer Center of Kansas, PA - Chanute	Chanute	Kansas
United States	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina
United States	John B. Amos Cancer Center	Columbus	Georgia
United States	Oakwood Cancer Center at Oakwood Hospital and Medical Center	Dearborn	Michigan
United States	Cancer Care Center of Decatur	Decatur	Illinois
United States	Charles B. Eberhart Cancer Center at DeKalb Medical Center	Decatur	Georgia
United States	Decatur Memorial Hospital Cancer Care Institute	Decatur	Illinois
United States	Kaiser Permanente - Denver	Denver	Colorado
United States	Josephine Ford Cancer Center at Henry Ford Hospital	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	Genesys Hurley Cancer Institute	Flint	Michigan
United States	Hurley Medical Center	Flint	Michigan
United States	Broward General Medical Center Cancer Center	Fort Lauderdale	Florida
United States	Cancer Center of Kansas - Fort Scott	Fort Scott	Kansas
United States	Kaiser Permanente - Fremont	Fremont	California
United States	Northeast Georgia Medical Center	Gainesville	Georgia
United States	Valley View Hospital Cancer Center	Glenwood Springs	Colorado
United States	Butterworth Hospital at Spectrum Health	Grand Rapids	Michigan
United States	CCOP - Grand Rapids	Grand Rapids	Michigan
United States	Lacks Cancer Center at Saint Mary's Health Care	Grand Rapids	Michigan
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	Marin Cancer Institute at Marin General Hospital	Greenbrae	California
United States	Moses Cone Regional Cancer Center at Wesley Long Community Hospital	Greensboro	North Carolina
United States	Van Elslander Cancer Center at St. John Hospital and Medical Center	Grosse Pointe Woods	Michigan
United States	Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center	Hartford	Connecticut
United States	Northern Montana Hospital	Havre	Montana
United States	Kaiser Permanente Medical Center - Hayward	Hayward	California
United States	St. Peter's Hospital	Helena	Montana
United States	Pardee Memorial Hospital	Hendersonville	North Carolina
United States	Kaiser Permanente - Moanalua Medical Center and Clinic	Honolulu	Hawaii
United States	Cancer Center of Kansas-Independence	Independence	Kansas
United States	Foote Memorial Hospital	Jackson	Michigan
United States	Glacier Oncology, PLLC	Kalispell	Montana
United States	Kalispell Medical Oncology at KRMC	Kalispell	Montana
United States	Good Samaritan Cancer Center at Good Samaritan Hospital	Kearney	Nebraska
United States	Columbia Basin Hematology	Kennewick	Washington
United States	Cancer Center of Kansas, PA - Kingman	Kingman	Kansas
United States	Kaiser Permanente - Lafayette	Lafayette	Colorado
United States	Sparrow Regional Cancer Center	Lansing	Michigan
United States	Lawrence Memorial Hospital	Lawrence	Kansas
United States	Gwinnett Medical Center	Lawrenceville	Georgia
United States	Lucille P. Markey Cancer Center at University of Kentucky	Lexington	Kentucky
United States	Cancer Center of Kansas, PA - Liberal	Liberal	Kansas
United States	St. Mary Mercy Hospital	Livonia	Michigan
United States	Kennestone Cancer Center at Wellstar Kennestone Hospital	Marietta	Georgia
United States	Tibotec Therapeutics - Division of Ortho Biotech Products, LP	Marysville	California
United States	Providence Milwaukie Hospital	Milwaukie	Oregon
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	Skagit Valley Hospital Cancer Care Center	Mount Vernon	Washington
United States	Mercy General Health Partners	Muskegon	Michigan
United States	Edward Hospital Cancer Center	Naperville	Illinois
United States	Cancer Center of Kansas, PA - Newton	Newton	Kansas
United States	Kaiser Permanente Medical Center - Oakland	Oakland	California
United States	Cancer Center of Kansas, PA - Parsons	Parsons	Kansas
United States	Regional Cancer Center at Singing River Hospital	Pascagoula	Mississippi
United States	Valley Medical Oncology Consultants - Pleasanton	Pleasanton	California
United States	St. Joseph Mercy Oakland	Pontiac	Michigan
United States	Mercy Regional Cancer Center at Mercy Hospital	Port Huron	Michigan
United States	Adventist Medical Center	Portland	Oregon
United States	CCOP - Columbia River Oncology Program	Portland	Oregon
United States	Providence Cancer Center at Providence Portland Medical Center	Portland	Oregon
United States	Providence St. Vincent Medical Center	Portland	Oregon
United States	Harrison Poulsbo Hematology and Onocology	Poulsbo	Washington
United States	Cancer Center of Kansas, PA - Pratt	Pratt	Kansas
United States	Kaiser Permanente Medical Center - Redwood City	Redwood City	California
United States	Annie Penn Cancer Center	Reidsville	North Carolina
United States	Kaiser Permanente Medical Center - Richmond	Richmond	California
United States	Southern Regional Medical Center	Riverdale	Georgia
United States	Highland Hospital of Rochester	Rochester	New York
United States	Interlakes Oncology/Hematology PC	Rochester	New York
United States	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York
United States	Harbin Clinic Cancer Center - Medical Oncology	Rome	Georgia
United States	Kaiser Permanente Medical Center - Roseville	Roseville	California
United States	Kaiser Permanente Medical Center - Sacramento	Sacramento	California
United States	South Sacramento Kaiser-Permanente Medical Center	Sacramento	California
United States	University of California Davis Cancer Center	Sacramento	California
United States	Seton Cancer Institute at Saint Mary's - Saginaw	Saginaw	Michigan
United States	Cancer Center of Kansas, PA - Salina	Salina	Kansas
United States	Tammy Walker Cancer Center at Salina Regional Health Center	Salina	Kansas
United States	California Pacific Medical Center - California Campus	San Francisco	California
United States	Kaiser Permanente Medical Center - San Francisco Geary Campus	San Francisco	California
United States	Kaiser Permanente Medical Center - Santa Teresa	San Jose	California
United States	Kaiser Foundation Hospital - San Rafael	San Rafael	California
United States	Sutter Health - Western Division Cancer Research Group	San Rafael	California
United States	Kaiser Permanente Medical Center - Santa Clara Kiely Campus	Santa Clara	California
United States	Kaiser Permanente Medical Center - Santa Rosa	Santa Rosa	California
United States	Nancy N. and J. C. Lewis Cancer and Research Pavilion at St. Joseph's/Candler	Savannah	Georgia
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Group Health Central Hospital	Seattle	Washington
United States	Harborview Medical Center	Seattle	Washington
United States	Minor and James Medical, PLLC	Seattle	Washington
United States	Polyclinic First Hill	Seattle	Washington
United States	Swedish Cancer Institute at Swedish Medical Center - First Hill Campus	Seattle	Washington
United States	University Cancer Center at University of Washington Medical Center	Seattle	Washington
United States	Welch Cancer Center at Sheridan Memorial Hospital	Sheridan	Wyoming
United States	Kaiser Permanente Medical Center - South San Francisco	South San Francisco	California
United States	Cancer Care Northwest - Spokane South	Spokane	Washington
United States	Evergreen Hematology and Oncology, PS	Spokane	Washington
United States	CCOP - Cancer Research for the Ozarks	Springfield	Missouri
United States	Hulston Cancer Center at Cox Medical Center South	Springfield	Missouri
United States	St. John's Regional Health Center	Springfield	Missouri
United States	Iredell Memorial Hospital	Statesville	North Carolina
United States	Kaiser Permanente Medical Facility - Stockton	Stockton	California
United States	Cotton-O'Neil Cancer Center	Topeka	Kansas
United States	Munson Medical Center	Traverse City	Michigan
United States	Tahoe Forest Cancer Center	Truckee	California
United States	Kaiser Permanente Medical Center - Vallejo	Vallejo	California
United States	Southwest Washington Medical Center Cancer Center	Vancouver	Washington
United States	Kaiser Permanente Medical Center - Walnut Creek	Walnut Creek	California
United States	St. John Macomb Hospital	Warren	Michigan
United States	Cancer Center of Kansas, PA - Wellington	Wellington	Kansas
United States	Wenatchee Valley Medical Center	Wenatchee	Washington
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	Cancer Center of Kansas, PA - Winfield	Winfield	Kansas
United States	Central Dupage Cancer Center	Winfield	Illinois
United States	Metro Health Hospital	Wyoming	Michigan

Sponsors (2)

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

Country where clinical trial is conducted

United States, 

References & Publications (2)

Mack PC, Moon J, West HJ, et al.: Molecular marker analysis of SWOG S0636, a phase II trial of erlotinib and bevacizumab in never-smokers with advanced NSCLC. [Abstract] J Clin Oncol 30 (Suppl 15): A-7552, 2012.

West HJ, Moon J, Hirsch FR, et al.: SWOG S0635 and S0636: Phase II trials in advanced-stage NSCLC of erlotinib (OSI-774) and bevacizumab in bronchioloalveolar carcinoma (BAC) and adenocarcinoma with BAC features (adenoBAC), and in never-smokers with primary NSCLC adenocarcinoma (adenoCa). [Abstract] J Clin Oncol 30 (Suppl 15): A-7517, 2012.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival	From date of registration to date of death due to any cause. Patients last known to be alive are censored at date of last contact.	Disease assessment is performed every 6 weeks for 18 weeks, then every 9-12 weeks until progression up to 2 years. After disease progression, patients must be followed every 3 months for 1 year and then every 6 months for a maximum of 3 years.
Secondary	Progression-free Survival	From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause. Patients last known to be alive and progression-free are censored at date of last contact. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v 1.0), as a 20% increase in the sum of longest diameters of target measurable lesions over smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline, or unequivocal progression of non-measurable disease in the opinion of the treating physician (an explanation must be provided) or appearance of any new lesion/site, or death due to disease without prior documentation of progression and without symptomatic deterioration.	Disease assessment is performed every 6 weeks for 18 weeks, then every 9-12 weeks until progression up to 2 years. After disease progression, patients must be followed every 3 months for 1 year and then every 6 months for a maximum of 3 years.
Secondary	Response Rate (Complete and Partial)	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0): Complete Response (CR), Disappearance of all measurable and non-measurable disease; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.; All target measurable lesions must be assessed using the same techniques as baseline.	Disease assessment is performed every 6 weeks for 18 weeks, then every 9-12 weeks until progression up to 2 years. After disease progression, patients must be followed every 3 months for 1 year and then every 6 months for a maximum of 3 years.
Secondary	Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs	Adverse Events (AEs) are reported by CTCAE Version 3.0. Only adverse events that are possibly, probably or definitely related to study drug are reported. Any CTCAE 3.0 event of Grade 3 (serious), Grade 4 (life threatening) or Grade 5 (fatal) which were deemed to be related to protocol treatment are included.	Toxicity assessment was evaluated after each cycle (21 days) while on protocol therapy.