Clinical trial NCT00770120: S0722: Everolimus in Treating Patients With Pleural Malignant Mesothelioma That Cannot Be Removed By Surgery
Official title: Phase II Trial of mTOR Inhibitor, Everolimus (RAD001), in Malignant Pleural Mesothelioma (MPM)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Malignant Mesothelioma
Keywords: recurrent malignant mesothelioma
stage II malignant mesothelioma
stage III malignant mesothelioma
stage IV malignant mesothelioma
Lead sponsor: SWOG Cancer Research Network
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2008-10-09
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

PURPOSE: This phase II trial is studying how well everolimus works in treating patients with pleural malignant mesothelioma that cannot be removed by surgery.

Detailed description: OBJECTIVES:

Primary

* To determine the 4-month progression-free survival in patients with unresectable malignant pleural mesothelioma treated with everolimus.

Secondary

* To determine the response rate (confirmed and unconfirmed, complete and partial responses) and disease control rate (response or stable disease) in patients with measurable disease by RECIST and modified RECIST criteria.
* To determine overall survival of these patients.
* To evaluate the frequency and severity of toxicities associated with this treatment regimen.

OUTLINE: This is a multicenter study.

Patients receive oral everolimus once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed malignant pleural mesothelioma

  * Unresectable disease
* Must have measurable or nonmeasurable disease by RECIST or modified RECIST criteria
* Must have received prior systemically administered\* platinum-based chemotherapy and meets the following criteria:

  * No more than 2 prior systemic therapeutic regimens allowed (including biologics, targeted, and immunotherapies)
  * At least 1 regimen must have been platinum-based
  * Neoadjuvant and/or adjuvant systemic therapy is not counted as a prior regimen, assuming ≥ 12 weeks have elapsed between the end of neoadjuvant/adjuvant therapy and development of progressive disease NOTE: \*Pleural space washing with cisplatin does not constitute systemic administration
* No known CNS metastases

PATIENT CHARACTERISTICS:

* Zubrod performance status 0-1
* ANC ≥ 1,500/mm³
* Platelet count ≥ 100,000/mm³
* Serum bilirubin normal
* AST or ALT ≤ 1.5 times upper limit of normal (ULN)
* Serum creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 50 mL/min
* Not pregnant or nursing
* Fertile patients must use effective contraception
* No evidence of bleeding diathesis or coagulopathy

  * Previous pulmonary embolism allowed provided the patient is on therapeutic low molecular weight heparin injections or warfarin AND no evidence of bleeding

    * Patients on therapeutic warfarin must have an INR of \< 5 within 28 days prior to registration
* No pathologic condition other than mesothelioma that carries a high risk of bleeding
* No known HIV positivity
* No gastrointestinal tract disease resulting in an inability to take oral or enteral medication via a feeding tube or a requirement for IV alimentation, or active peptic ulcer disease
* No other prior malignancy allowed except for any of the following:

  * Adequately treated basal cell or squamous cell skin cancer
  * In situ cervical cancer
  * Adequately treated stage I or II cancer from which the patient is currently in complete remission
  * Any other cancer from which patient has been disease-free for 5 years

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics
* Recovered from all prior therapy
* At least 28 days since prior systemic therapy (42 days for nitrosoureas or mitomycin C)
* At least 28 days since prior thoracic or other major surgery (e.g., pleurectomy or pleurodesis) and no anticipated need for major surgical procedures during study
* At least 14 days since prior radiotherapy
* No prior surgical procedure affecting absorption
* No prior chronic, systemic corticosteroids or other immunosuppressive agent, except corticosteroids equivalent to prednisone ≤ 20 mg daily

  * Must have been on a stable dosage regimen for ≥ 4 weeks
  * Topical and inhaled corticosteroids allowed
* No prior mTOR inhibitor therapy (i.e., rapamycin, everolimus, or temsirolimus)
* No concurrent immunization with attenuated live vaccines
* No concurrent antiretroviral therapy for HIV-positive patients
* No other concurrent investigational therapy
* No other concurrent anticancer agents

Primary outcomes:
measure: Progression-Free Survival
timeFrame: Every 8 weeks until disease progression, up to 3 years.
Secondary outcomes:
measure: Response
timeFrame: Every 8 weeks until disease progression, up to 3 years.
measure: Overall Survival
timeFrame: Every 8 weeks until disease progression, up to 3 years.
measure: Frequency and Severity of Toxicities
timeFrame: Weekly during the first 8 weeks of treatment, then every 4 weeks while on treatment, then every 8 weeks until disease progression, then every 6 months thereafter.
Other outcomes:
Locations:
city: Tucson
country: United States
facility: Arizona Cancer Center at University of Arizona Health Sciences Center
state: Arizona
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: Orange
country: United States
facility: Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center
state: California
city: Pleasanton
country: United States
facility: Valley Medical Oncology Consultants - Pleasanton
state: California
city: Sacramento
country: United States
facility: University of California Davis Cancer Center
state: California
city: Alamosa
country: United States
facility: San Luis Valley Regional Medical Center
state: Colorado
city: Aurora
country: United States
facility: University of Colorado Cancer Center at UC Health Sciences Center
state: Colorado
city: Edwards
country: United States
facility: Shaw Regional Cancer Center
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: Hartford
country: United States
facility: Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center
state: Connecticut
city: Gainesville
country: United States
facility: Northeast Georgia Medical Center
state: Georgia
city: Decatur
country: United States
facility: Decatur Memorial Hospital Cancer Care Institute
state: Illinois
city: Naperville
country: United States
facility: Edward Hospital Cancer Center
state: Illinois
city: Springfield
country: United States
facility: Regional Cancer Center at Memorial Medical Center
state: Illinois
city: Beech Grove
country: United States
facility: St. Francis Hospital and Health Centers - Beech Grove Campus
state: Indiana
city: Richmond
country: United States
facility: Reid Hospital & Health Care Services
state: Indiana
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: 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: Cancer Center of Kansas, PA - Liberal
state: Kansas
city: Newton
country: United States
facility: Cancer Center of Kansas, PA - Newton
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: Salina
country: United States
facility: Tammy Walker Cancer Center at Salina Regional Health 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: Winfield
country: United States
facility: Cancer Center of Kansas, PA - Winfield
state: Kansas
city: Ann Arbor
country: United States
facility: Saint Joseph Mercy Cancer Center
state: Michigan
city: Ann Arbor
country: United States
facility: CCOP - Michigan Cancer Research Consortium
state: Michigan
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Dearborn
country: United States
facility: Oakwood Cancer Center at Oakwood Hospital and Medical Center
state: Michigan
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: Flint
country: United States
facility: Genesys Hurley Cancer Institute
state: Michigan
city: Flint
country: United States
facility: Hurley Medical Center
state: Michigan
city: Grosse Pointe Woods
country: United States
facility: Van Elslander Cancer Center at St. John Hospital and Medical Center
state: Michigan
city: Jackson
country: United States
facility: Foote Memorial Hospital
state: Michigan
city: Lansing
country: United States
facility: Sparrow Regional Cancer Center
state: Michigan
city: Livonia
country: United States
facility: St. Mary Mercy Hospital
state: Michigan
city: Pontiac
country: United States
facility: St. Joseph Mercy Oakland
state: Michigan
city: Port Huron
country: United States
facility: Mercy Regional Cancer Center at Mercy Hospital
state: Michigan
city: Saginaw
country: United States
facility: Seton Cancer Institute at Saint Mary's - Saginaw
state: Michigan
city: Warren
country: United States
facility: St. John Macomb Hospital
state: Michigan
city: Billings
country: United States
facility: CCOP - Montana Cancer Consortium
state: Montana
city: Billings
country: United States
facility: St. Vincent Healthcare Cancer Care Services
state: Montana
city: Billings
country: United States
facility: Hematology-Oncology Centers of the Northern Rockies - Billings
state: Montana
city: Billings
country: United States
facility: Billings Clinic - Downtown
state: Montana
city: Bozeman
country: United States
facility: Bozeman Deaconess Cancer Center
state: Montana
city: Butte
country: United States
facility: St. James Healthcare Cancer Care
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: 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: 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: Albuquerque
country: United States
facility: University of New Mexico Cancer Center
state: New Mexico
city: Charlotte
country: United States
facility: Presbyterian Cancer Center at Presbyterian Hospital
state: North Carolina
city: Goldsboro
country: United States
facility: Wayne Memorial Hospital, Incorporated
state: North Carolina
city: Statesville
country: United States
facility: Iredell Memorial Hospital
state: North Carolina
city: Bellefontaine
country: United States
facility: Mary Rutan Hospital
state: Ohio
city: Chillicothe
country: United States
facility: Adena Regional Medical Center
state: Ohio
city: Columbus
country: United States
facility: Riverside Methodist Hospital Cancer Care
state: Ohio
city: Columbus
country: United States
facility: CCOP - Columbus
state: Ohio
city: Columbus
country: United States
facility: Grant Medical Center Cancer Care
state: Ohio
city: Columbus
country: United States
facility: Mount Carmel Health - West Hospital
state: Ohio
city: Columbus
country: United States
facility: Doctors Hospital at Ohio Health
state: Ohio
city: Dayton
country: United States
facility: Grandview Hospital
state: Ohio
city: Dayton
country: United States
facility: Good Samaritan Hospital
state: Ohio
city: Dayton
country: United States
facility: David L. Rike Cancer Center at Miami Valley Hospital
state: Ohio
city: Dayton
country: United States
facility: Samaritan North Cancer Care Center
state: Ohio
city: Dayton
country: United States
facility: CCOP - Dayton
state: Ohio
city: Delaware
country: United States
facility: Grady Memorial Hospital
state: Ohio
city: Findlay
country: United States
facility: Blanchard Valley Medical Associates
state: Ohio
city: Franklin
country: United States
facility: Middletown Regional Hospital
state: Ohio
city: Greenville
country: United States
facility: Wayne Hospital
state: Ohio
city: Kettering
country: United States
facility: Charles F. Kettering Memorial Hospital
state: Ohio
city: Lancaster
country: United States
facility: Fairfield Medical Center
state: Ohio
city: Marietta
country: United States
facility: Strecker Cancer Center at Marietta Memorial Hospital
state: Ohio
city: Mount Vernon
country: United States
facility: Knox Community Hospital
state: Ohio
city: Newark
country: United States
facility: Licking Memorial Cancer Care Program at Licking Memorial Hospital
state: Ohio
city: Springfield
country: United States
facility: Community Hospital of Springfield and Clark County
state: Ohio
city: Troy
country: United States
facility: UVMC Cancer Care Center at Upper Valley Medical Center
state: Ohio
city: Westerville
country: United States
facility: Mount Carmel St. Ann's Cancer Center
state: Ohio
city: Wilmington
country: United States
facility: Clinton Memorial Hospital
state: Ohio
city: Xenia
country: United States
facility: Ruth G. McMillan Cancer Center at Greene Memorial Hospital
state: Ohio
city: Zanesville
country: United States
facility: Genesis - Good Samaritan Hospital
state: Ohio
city: Clackamas
country: United States
facility: Clackamas Radiation Oncology Center
state: Oregon
city: Milwaukie
country: United States
facility: Providence Milwaukie Hospital
state: Oregon
city: Newberg
country: United States
facility: Providence Newberg Medical Center
state: Oregon
city: Oregon City
country: United States
facility: Willamette Falls Hospital
state: Oregon
city: Portland
country: United States
facility: Providence Cancer Center at Providence Portland Medical Center
state: Oregon
city: Portland
country: United States
facility: CCOP - Columbia River Oncology Program
state: Oregon
city: Portland
country: United States
facility: Providence St. Vincent Medical Center
state: Oregon
city: Kingsport
country: United States
facility: Christine LaGuardia Phillips Cancer Center at Wellmont Holston Valley Medical Center
state: Tennessee
city: Knoxville
country: United States
facility: U.T. Medical Center Cancer Institute
state: Tennessee
city: Houston
country: United States
facility: M. D. Anderson Cancer Center at University of Texas
state: Texas
city: Danville
country: United States
facility: Danville Regional Medical Center
state: Virginia
city: Norton
country: United States
facility: Southwest Virginia Regional Cancer Center at Wellmonth Health
state: Virginia
city: Bellingham
country: United States
facility: St. Joseph Cancer Center
state: Washington
city: Bremerton
country: United States
facility: Olympic Hematology and Oncology
state: Washington
city: Kennewick
country: United States
facility: Columbia Basin Hematology
state: Washington
city: Mount Vernon
country: United States
facility: Skagit Valley Hospital Cancer Care Center
state: Washington
city: Poulsbo
country: United States
facility: Harrison Poulsbo Hematology and Onocology
state: Washington
city: Seattle
country: United States
facility: Harborview Medical Center
state: Washington
city: Seattle
country: United States
facility: Minor and James Medical, PLLC
state: Washington
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Seattle
country: United States
facility: Group Health Central Hospital
state: Washington
city: Seattle
country: United States
facility: Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
state: Washington
city: Seattle
country: United States
facility: University Cancer Center at University of Washington Medical Center
state: Washington
city: Spokane
country: United States
facility: Cancer Care Northwest - Spokane South
state: Washington
city: Spokane
country: United States
facility: Evergreen Hematology and Oncology, PS
state: Washington
city: Vancouver
country: United States
facility: Southwest Washington Medical Center Cancer Center
state: Washington
city: Vancouver
country: United States
facility: Northwest Cancer Specialists at Vancouver Cancer Center
state: Washington
city: Wenatchee
country: United States
facility: Wenatchee Valley Medical Center
state: Washington
city: Casper
country: United States
facility: Rocky Mountain Oncology
state: Wyoming
city: Sheridan
country: United States
facility: Welch Cancer Center at Sheridan Memorial Hospital
state: Wyoming
Study officials:
affiliation: Chao Family Comprehensive Cancer Center
name: Sai-Hong I. Ou, MD, PhD
role: STUDY_CHAIR
affiliation: University of Arizona
name: Linda Garland, MD
role: STUDY_CHAIR
References:
citation: Ou SH, Moon J, Garland LL, Mack PC, Testa JR, Tsao AS, Wozniak AJ, Gandara DR. SWOG S0722: phase II study of mTOR inhibitor everolimus (RAD001) in advanced malignant pleural mesothelioma (MPM). J Thorac Oncol. 2015 Feb;10(2):387-91. doi: 10.1097/JTO.0000000000000360.