S0722: Everolimus in Treating Patients With Pleural Malignant Mesothelioma That Cannot Be Removed By Surgery

February 19, 2020 updated by: Southwest Oncology Group

Phase II Trial of mTOR Inhibitor, Everolimus (RAD001), in Malignant Pleural Mesothelioma (MPM)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

61

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Tucson, Arizona, United States, 85724-5024
        • Arizona Cancer Center at University of Arizona Health Sciences 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
      • Orange, California, United States, 92868
        • Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center
      • Pleasanton, California, United States, 94588
        • Valley Medical Oncology Consultants - Pleasanton
      • Sacramento, California, United States, 95817
        • University of California Davis Cancer Center
    • Colorado
      • Alamosa, Colorado, United States, 81101
        • San Luis Valley Regional Medical Center
      • Aurora, Colorado, United States, 80045
        • University of Colorado Cancer Center at UC Health Sciences Center
      • Edwards, Colorado, United States, 81632
        • Shaw Regional Cancer Center
      • Glenwood Springs, Colorado, United States, 81601
        • Valley View Hospital Cancer Center
      • Montrose, Colorado, United States, 81401
        • Montrose Memorial Hospital Cancer Center
    • Connecticut
      • Hartford, Connecticut, United States, 06105
        • Saint Francis/Mount Sinai Regional Cancer Center at Saint Francis Hospital and Medical Center
    • Georgia
      • Gainesville, Georgia, United States, 30501
        • Northeast Georgia Medical Center
    • Illinois
      • Decatur, Illinois, United States, 62526
        • Decatur Memorial Hospital Cancer Care Institute
      • Naperville, Illinois, United States, 60540
        • Edward Hospital Cancer Center
      • Springfield, Illinois, United States, 62781-0001
        • Regional Cancer Center at Memorial Medical Center
    • Indiana
      • Beech Grove, Indiana, United States, 46107
        • St. Francis Hospital and Health Centers - Beech Grove Campus
      • Richmond, Indiana, United States, 47374
        • Reid Hospital & Health Care Services
    • Kansas
      • 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
      • Kingman, Kansas, United States, 67068
        • Cancer Center of Kansas, PA - Kingman
      • Lawrence, Kansas, United States, 66044
        • Lawrence Memorial Hospital
      • Liberal, Kansas, United States, 67905
        • Cancer Center of Kansas, PA - Liberal
      • Newton, Kansas, United States, 67114
        • Cancer Center of Kansas, PA - Newton
      • 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, 67401
        • Cancer Center of Kansas, PA - Salina
      • Salina, Kansas, United States, 67401
        • Tammy Walker Cancer Center at Salina Regional Health Center
      • Wellington, Kansas, United States, 67152
        • Cancer Center of Kansas, PA - Wellington
      • 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
    • Michigan
      • Ann Arbor, Michigan, United States, 48109-0942
        • University Of Michigan Comprehensive Cancer Center
      • Ann Arbor, Michigan, United States, 48106-0995
        • Saint Joseph Mercy Cancer Center
      • Ann Arbor, Michigan, United States, 48106
        • CCOP - Michigan Cancer Research Consortium
      • Dearborn, Michigan, United States, 48123-2500
        • Oakwood Cancer Center at Oakwood Hospital and Medical Center
      • Detroit, Michigan, United States, 48201-1379
        • Barbara Ann Karmanos Cancer Institute
      • Flint, Michigan, United States, 48503
        • Hurley Medical Center
      • Flint, Michigan, United States, 48503
        • Genesys Hurley Cancer Institute
      • Grosse Pointe Woods, Michigan, United States, 48236
        • Van Elslander Cancer Center at St. John Hospital and Medical Center
      • Jackson, Michigan, United States, 49201
        • Foote Memorial Hospital
      • Lansing, Michigan, United States, 48912-1811
        • Sparrow Regional Cancer Center
      • Livonia, Michigan, United States, 48154
        • St. Mary Mercy Hospital
      • Pontiac, Michigan, United States, 48341-2985
        • St. Joseph Mercy Oakland
      • Port Huron, Michigan, United States, 48060
        • Mercy Regional Cancer Center at Mercy Hospital
      • Saginaw, Michigan, United States, 48601
        • Seton Cancer Institute at Saint Mary's - Saginaw
      • Warren, Michigan, United States, 48093
        • St. John Macomb Hospital
    • Montana
      • Billings, Montana, United States, 59101
        • CCOP - Montana Cancer Consortium
      • Billings, Montana, United States, 59101
        • St. Vincent Healthcare Cancer Care Services
      • Billings, Montana, United States, 59107-7000
        • Billings Clinic - Downtown
      • Billings, Montana, United States, 59102
        • Hematology-Oncology Centers of the Northern Rockies - Billings
      • Bozeman, Montana, United States, 59715
        • Bozeman Deaconess Cancer Center
      • 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
        • 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, 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
    • New Mexico
      • Albuquerque, New Mexico, United States, 87131-5636
        • University of New Mexico Cancer Center
    • North Carolina
      • Charlotte, North Carolina, United States, 28233-3549
        • Presbyterian Cancer Center at Presbyterian Hospital
      • Goldsboro, North Carolina, United States, 27534
        • Wayne Memorial Hospital, Incorporated
      • Statesville, North Carolina, United States, 28677
        • Iredell Memorial Hospital
    • Ohio
      • Bellefontaine, Ohio, United States, 43311
        • Mary Rutan Hospital
      • Chillicothe, Ohio, United States, 45601
        • Adena Regional Medical Center
      • Columbus, Ohio, United States, 43214-3998
        • Riverside Methodist Hospital Cancer Care
      • Columbus, Ohio, United States, 43222
        • Mount Carmel Health - West Hospital
      • Columbus, Ohio, United States, 43215
        • CCOP - Columbus
      • Columbus, Ohio, United States, 43215
        • Grant Medical Center Cancer Care
      • Columbus, Ohio, United States, 43228
        • Doctors Hospital at Ohio Health
      • Dayton, Ohio, United States, 45405
        • Grandview Hospital
      • Dayton, Ohio, United States, 45406
        • Good Samaritan Hospital
      • Dayton, Ohio, United States, 45409
        • David L. Rike Cancer Center at Miami Valley Hospital
      • Dayton, Ohio, United States, 45415
        • Samaritan North Cancer Care Center
      • Dayton, Ohio, United States, 45420
        • CCOP - Dayton
      • Delaware, Ohio, United States, 43015
        • Grady Memorial Hospital
      • Findlay, Ohio, United States, 45840
        • Blanchard Valley Medical Associates
      • Franklin, Ohio, United States, 45005-1066
        • Middletown Regional Hospital
      • Greenville, Ohio, United States, 45331
        • Wayne Hospital
      • Kettering, Ohio, United States, 45429
        • Charles F. Kettering Memorial Hospital
      • Lancaster, Ohio, United States, 43130
        • Fairfield Medical Center
      • Marietta, Ohio, United States, 45750
        • Strecker Cancer Center at Marietta Memorial Hospital
      • Mount Vernon, Ohio, United States, 43050
        • Knox Community Hospital
      • Newark, Ohio, United States, 43055
        • Licking Memorial Cancer Care Program at Licking Memorial Hospital
      • Springfield, Ohio, United States, 45505
        • Community Hospital of Springfield and Clark County
      • Troy, Ohio, United States, 45373-1300
        • UVMC Cancer Care Center at Upper Valley Medical Center
      • Westerville, Ohio, United States, 43081
        • Mount Carmel St. Ann's Cancer Center
      • Wilmington, Ohio, United States, 45177
        • Clinton Memorial Hospital
      • Xenia, Ohio, United States, 45385
        • Ruth G. McMillan Cancer Center at Greene Memorial Hospital
      • Zanesville, Ohio, United States, 43701
        • Genesis - Good Samaritan Hospital
    • Oregon
      • Clackamas, Oregon, United States, 97015
        • Clackamas Radiation Oncology Center
      • Milwaukie, Oregon, United States, 97222
        • Providence Milwaukie Hospital
      • Newberg, Oregon, United States, 97132
        • Providence Newberg Medical Center
      • Oregon City, Oregon, United States, 97045
        • Willamette Falls Hospital
      • Portland, Oregon, United States, 97213-2967
        • Providence Cancer Center at Providence Portland Medical Center
      • Portland, Oregon, United States, 97225
        • CCOP - Columbia River Oncology Program
      • Portland, Oregon, United States, 97225
        • Providence St. Vincent Medical Center
    • Tennessee
      • Kingsport, Tennessee, United States, 37662
        • Christine LaGuardia Phillips Cancer Center at Wellmont Holston Valley Medical Center
      • Knoxville, Tennessee, United States, 37920-6999
        • U.T. Medical Center Cancer Institute
    • Texas
      • Houston, Texas, United States, 77030-4009
        • M. D. Anderson Cancer Center at University of Texas
    • Virginia
      • Danville, Virginia, United States, 24541
        • Danville Regional Medical Center
      • Norton, Virginia, United States, 24273
        • Southwest Virginia Regional Cancer Center at Wellmonth Health
    • Washington
      • Bellingham, Washington, United States, 98225
        • St. Joseph Cancer Center
      • Bremerton, Washington, United States, 98310
        • Olympic Hematology and Oncology
      • Kennewick, Washington, United States, 99336
        • Columbia Basin Hematology
      • Mount Vernon, Washington, United States, 98273
        • Skagit Valley Hospital Cancer Care Center
      • Poulsbo, Washington, United States, 98370
        • Harrison Poulsbo Hematology and Onocology
      • Seattle, Washington, United States, 98109
        • Fred Hutchinson Cancer Research Center
      • Seattle, Washington, United States, 98104
        • Harborview Medical Center
      • Seattle, Washington, United States, 98104
        • Minor and James Medical, PLLC
      • Seattle, Washington, United States, 98112
        • Group Health Central Hospital
      • Seattle, Washington, United States, 98122-4307
        • Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
      • Seattle, Washington, United States, 98195
        • University Cancer Center at University of Washington Medical Center
      • Spokane, Washington, United States, 99202
        • Cancer Care Northwest - Spokane South
      • Spokane, Washington, United States, 99218
        • Evergreen Hematology and Oncology, PS
      • Vancouver, Washington, United States, 98684
        • Northwest Cancer Specialists at Vancouver Cancer Center
      • Vancouver, Washington, United States, 98668
        • Southwest Washington Medical Center Cancer Center
      • Wenatchee, Washington, United States, 98801-2028
        • Wenatchee Valley Medical Center
    • Wyoming
      • Casper, Wyoming, United States, 82609
        • Rocky Mountain Oncology
      • Sheridan, Wyoming, United States, 82801
        • Welch Cancer Center at Sheridan Memorial Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 120 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Everolimus
Daily oral Everolimus 10 mg/day
Drug: everolimus

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-Free Survival
Time Frame: Every 8 weeks until disease progression, up to 3 years.
Progression-Free Survival was defined as the duration from the date of registration until the date of disease progression per RECIST or death due to any cause. Patients known to be alive without evidence of disease progression were censored at the date of last contact. Disease progression was defined as a >= 20% increase over nadir in the sum of longest diameters of target lesions, unequivocal progression of non-target lesions in the opinion of the treating investigator, appearance of new lesions, symptomatic deterioration, or death due to disease
Every 8 weeks until disease progression, up to 3 years.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Response
Time Frame: Every 8 weeks until disease progression, up to 3 years.
A response was defined as either a confirmed or unconfirmed complete or partial responses as defined by RECIST. A complete response (CR) was defined as the disappearance of all disease. A partial response (PR) was defined as a >= 30% decrease in the sum of longest diameters of target lesions. A CR or PR was considered confirmed if two consecutive determinations were made at least 4 weeks apart.
Every 8 weeks until disease progression, up to 3 years.
Overall Survival
Time Frame: Every 8 weeks until disease progression, up to 3 years.
Overall survival was defined as the duration between the date of enrollment and the date of death due to any cause. Patients last known to be alive were censored at the date of last contact.
Every 8 weeks until disease progression, up to 3 years.
Frequency and Severity of Toxicities
Time Frame: 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.
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.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Southwest Oncology Group

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Sai-Hong I. Ou, MD, PhD, Chao Family Comprehensive Cancer Center
  • Study Chair: Linda Garland, MD, University of Arizona

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2008

Primary Completion (Actual)

April 1, 2014

Study Completion (Actual)

April 1, 2014

Study Registration Dates

First Submitted

October 8, 2008

First Submitted That Met QC Criteria

October 8, 2008

First Posted (Estimate)

October 9, 2008

Study Record Updates

Last Update Posted (Actual)

March 6, 2020

Last Update Submitted That Met QC Criteria

February 19, 2020

Last Verified

February 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000616162
  • U10CA032102 (U.S. NIH Grant/Contract)
  • S0722 (Other Identifier: SWOG)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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