S0330 Erlotinib in Treating Patients With Unresectable or Metastatic Malignant Peripheral Nerve Sheath Tumor

U.S./Canada Sarcoma Intergroup Study of OSI-774 in Malignant Peripheral Nerve Sheath Tumors, Phase II

RATIONALE: Erlotinib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth.

PURPOSE: This phase II trial is studying how well erlotinib works in treating patients with unresectable or metastatic malignant peripheral nerve sheath tumor.

Study Overview

• Status: Completed
• Conditions: Sarcoma
• Intervention / Treatment: Drug: erlotinib hydrochloride

Detailed Description

OBJECTIVES:

• Determine response (confirmed, complete, and partial) in patients with unresectable or metastatic malignant peripheral nerve sheath tumor when treated with erlotinib.
• Determine the qualitative and quantitative toxic effects of this drug in these patients.
• Correlate, preliminarily, indicators of epidermal growth factor receptor (EGFR) function (e.g., expression, phosphorylation, or markers of signal transduction downstream of EGFR) with response and progression-free and overall survival in patients treated with this drug.
• Determine the feasibility of accruing these patients in the cooperative group setting.

OUTLINE: This is a multicenter study.

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

Patients who achieve at least a confirmed partial response and become resectable undergo surgical resection (with or without radiotherapy) and then receive 2 additional courses of erlotinib. Patients with responding disease who do not become resectable continue erlotinib as above. Patients achieving a complete response (CR) receive 2 additional courses of erlotinib beyond the CR.

Patients are followed every 6 months for 2 years and then annually for 3 years.

PROJECTED ACCRUAL: A total of 20-40 patients will be accrued for this study.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
  • California
    • Davis, California, United States, 95616
      • University of California Davis Cancer Center
    • Martinez, California, United States, 94553-3156
      • Contra Costa Regional Medical Center
  • Colorado
    • Denver, Colorado, United States, 80204
      • St. Anthony Central Hospital
    • Denver, Colorado, United States, 80217-3364
      • University of Colorado Cancer Center at University of Colorado Health Sciences Center
    • Montrose, Colorado, United States, 81401
      • Montrose Memorial Hospital Cancer Center
    • Westminster, Colorado, United States, 80030
      • St. Anthony North Hospital
    • Wheat Ridge, Colorado, United States, 80033
      • Exempla Lutheran Medical Center
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Piedmont Hospital
    • Atlanta, Georgia, United States, 30342
      • Saint Joseph's Hospital of Atlanta
    • Atlanta, Georgia, United States, 30342
      • CCOP - Atlanta Regional
    • Atlanta, Georgia, United States, 30342
      • Northside Hospital Cancer Center
    • Austell, Georgia, United States, 30106
      • WellStar Cobb Hospital
    • Decatur, Georgia, United States, 30033
      • Charles B. Eberhart Cancer Center at DeKalb Medical Center
    • Lawrenceville, Georgia, United States, 30045
      • Gwinnett Medical Center
    • Marietta, Georgia, United States, 30060
      • Kennestone Cancer Center at Wellstar Kennestone Hospital
    • Riverdale, Georgia, United States, 30274
      • Southern Regional Medical Center
  • Illinois
    • Maywood, Illinois, United States, 60153
      • Cardinal Bernardin Cancer Center at Loyola University Medical 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
  • Iowa
    • Ames, Iowa, United States, 50010
      • McFarland Clinic, P.C.
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70806
      • Baton Rouge General Regional Cancer Center
    • Baton Rouge, Louisiana, United States, 70809
      • Mary Bird Perkins Cancer Center - Baton Rouge
    • New Orleans, Louisiana, United States, 70112
      • MBCCOP - LSU Health Sciences Center
    • New Orleans, Louisiana, United States, 70112
      • Medical Center of Louisiana - New Orleans
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Comprehensive Cancer Center
    • Battle Creek, Michigan, United States, 49017
      • Battle Creek Health System Cancer Care Center
    • Big Rapids, Michigan, United States, 49307
      • Mecosta County General Hospital
    • Grand Rapids, Michigan, United States, 49503
      • CCOP - Grand Rapids
    • Grand Rapids, Michigan, United States, 49503
      • Lacks Cancer Center at Saint Mary's Mercy Medical Center
    • Grand Rapids, Michigan, United States, 49503
      • Spectrum Health Cancer Care - Butterworth Campus
    • Grand Rapids, Michigan, United States, 49506
      • Metropolitan Hospital
    • Grand Rapids, Michigan, United States, 49506
      • Spectrum Health Hospital - Blodgett Campus
    • Holland, Michigan, United States, 49423
      • Holland Community Hospital
    • Muskegon, Michigan, United States, 49443
      • Hackley Hospital
    • Petoskey, Michigan, United States, 49770
      • Northern Michigan Hospital
    • Traverse City, Michigan, United States, 49684
      • Munson Medical Center
  • Montana
    • Billings, Montana, United States, 59101
      • CCOP - Montana Cancer Consortium
    • Billings, Montana, United States, 59101
      • Northern Rockies Radiation Oncology Center
    • Billings, Montana, United States, 59101
      • Deaconess Billings Clinic - Downtown
    • Billings, Montana, United States, 59101
      • St. Vincent Healthcare
    • Billings, Montana, United States, 59107
      • Deaconess Billings Clinic Cancer Center
    • Bozeman, Montana, United States, 59715
      • Bozeman Deaconess Hospital
    • Butte, Montana, United States, 59701
      • St. James Community Hospital
    • Helena, Montana, United States, 59601
      • St. Peter's Hospital
    • Kalispell, Montana, United States, 59901
      • Kalispell Regional Medical Center
    • Miles City, Montana, United States, 59301
      • Eastern Montana Cancer Center
    • Missoula, Montana, United States, 59801
      • Community Medical Center
    • Missoula, Montana, United States, 59802
      • Montana Cancer Center at St. Patrick Hospital and Health Sciences Center
  • Nebraska
    • Omaha, Nebraska, United States, 68114
      • Methodist Cancer Center at Methodist Hospital - Omaha
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Blumenthal Cancer Center at Carolinas Medical Center
    • Goldsboro, North Carolina, United States, 27534
      • Wayne Memorial Hospital, Incorporated
    • Wilson, North Carolina, United States, 27893
      • Wilson Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Taussig Cancer Center
    • Dayton, Ohio, United States, 45428
      • Veterans Affairs Medical Center - Dayton
    • 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, 45429
      • CCOP - Dayton
    • Independence, Ohio, United States, 44131
      • Community Oncology Group - Independence
    • Kettering, Ohio, United States, 45429
      • Charles F. Kettering Memorial Hospital
    • Middletown, Ohio, United States, 45044
      • Middletown Regional Hospital
    • Troy, Ohio, United States, 45373
      • UVMC Cancer Care Center at Upper Valley Medical Center
    • Wooster, Ohio, United States, 44691
      • Cleveland Clinic - Wooster
    • Xenia, Ohio, United States, 45385
      • Ruth G. McMillan Cancer Center at Greene Memorial Hospital
  • Oregon
    • Gresham, Oregon, United States, 97030
      • Legacy Mount Hood Medical Center
    • Milwaukie, Oregon, United States, 97222
      • Providence Milwaukie Hospital
    • Portland, Oregon, United States, 97225
      • CCOP - Columbia River Oncology Program
    • Portland, Oregon, United States, 97225
      • Providence St. Vincent Medical Center
    • Portland, Oregon, United States, 97210
      • Comprehensive Cancer Center at Legacy Good Samaritan Hospital & Medical Center
    • Portland, Oregon, United States, 97213
      • Providence Cancer Center at Providence Portland Medical Center
    • Portland, Oregon, United States, 97227
      • Institute of Oncology at Vilnius University
    • Portland, Oregon, United States, 97239
      • Cancer Institute at Oregon Health and Science University
    • Tualatin, Oregon, United States, 97062
      • Legacy Meridian Park Hospital
  • Virginia
    • Danville, Virginia, United States, 24541
      • Danville Regional Medical Center
  • Washington
    • Auburn, Washington, United States, 98002
      • Auburn Regional Center for Cancer Care
    • Bellingham, Washington, United States, 98225
      • St. Joseph Hospital Community Cancer Center
    • Bremerton, Washington, United States, 98310
      • Olympic Hematology and Oncology
    • Centralia, Washington, United States, 98531
      • Regional Cancer Center at Providence Hospital
    • Federal Way, Washington, United States, 98003
      • St. Francis Hospital
    • Mount Vernon, Washington, United States, 98273
      • Skagit Valley Hospital Cancer Care Center
    • Olympia, Washington, United States, 98507
      • Capital Medical Center
    • Olympia, Washington, United States, 95806
      • Providence St. Peter Hospital Regional Cancer Center
    • Puyallup, Washington, United States, 98372
      • Good Samaritan Cancer Center
    • Seattle, Washington, United States, 98104
      • Harborview Medical Center
    • Seattle, Washington, United States, 98104
      • Fred Hutchinson Cancer Research Center
    • Seattle, Washington, United States, 98195
      • University Cancer Center at University of Washington Medical Center
    • Seattle, Washington, United States, 98104
      • Group Health Central Hospital
    • Seattle, Washington, United States, 98114
      • Swedish Cancer Institute at Swedish Medical Center - First Hill Campus
    • Sedro-Woolley, Washington, United States, 98284
      • North Puget Oncology at United General Hospital
    • Spokane, Washington, United States, 99202
      • Cancer Care Northwest - Spokane South
    • Tacoma, Washington, United States, 98405
      • Allenmore Hospital
    • Tacoma, Washington, United States, 98405
      • CCOP - Northwest
    • Tacoma, Washington, United States, 98499
      • St. Clare Hospital
    • Tacoma, Washington, United States, 98405
      • St. Joseph Medical Center at Franciscan Health System
    • Vancouver, Washington, United States, 98668
      • Southwest Washington Medical Center Cancer Center
    • Wenatchee, Washington, United States, 98801
      • Central Washington Hospital
    • Wenatchee, Washington, United States, 98801
      • Wenatchee Valley Clinic
  • West Virginia
    • Parkersburg, West Virginia, United States, 26101
      • Community Comprehensive Cancer Center at Camden-Clark Memorial Hospital
  • Wyoming
    • Sheridan, Wyoming, United States, 82801
      • Welch Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 118 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed malignant peripheral nerve sheath tumor

  • Malignant schwannoma or neurofibrosarcoma
  • Clinical evidence of unresectable or metastatic disease
• Measurable disease
• No known current CNS metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Zubrod 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count greater than 1,500/mm^3
• Platelet count greater than 100,000/mm^3

Hepatic

• Bilirubin less than 1.5 times upper limit of normal (ULN)
• SGOT or SGPT less than 1.5 times ULN (5 times ULN for patients with documented liver metastases)

Renal

• Creatinine no greater than 1.5 times ULN
• Creatinine clearance greater than 60 mL/min

Ophthalmic

• No known history of any of the following corneal diseases:

  • Dry eye syndrome
  • Sjögren's syndrome
  • Keratoconjunctivitis sicca
  • Exposure keratopathy
  • Fuch's dystrophy
• No other active disorders of the cornea

Gastrointestinal

• No gastrointestinal tract disease resulting in an inability to take oral medication or a requirement for IV alimentation
• No active peptic ulcer disease
• No intractable nausea or vomiting
• Able to swallow medications OR receive enteral medications via gastrostomy feeding tube

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer currently in complete remission

PRIOR CONCURRENT THERAPY:

Biologic therapy

• More than 28 days since prior biologic therapy for this malignancy

Chemotherapy

• More than 28 days since prior chemotherapy for this malignancy

Endocrine therapy

• Not specified

Radiotherapy

• More than 60 days since prior radiotherapy to the target lesion with subsequent documented progression
• More than 60 days since prior radiofrequency ablation to the target lesion with subsequent documented progression
• No concurrent radiotherapy

Surgery

• At least 3 weeks since prior major surgery and recovered
• No prior surgical procedure affecting absorption

Other

• More than 28 days since prior investigational drugs for this malignancy
• More than 60 days since prior embolization to the target lesion with subsequent documented progression
• No prior epidermal growth factor receptor-targeting therapy
• No concurrent antiretroviral therapy for HIV-positive patients
• No other concurrent investigational or commercial agents or therapies for the malignancy

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (OSI-774); Drug: erlotinib hydrochloride Other Names: OSI-774 150 mg per day, daily until disease progression	Drug: erlotinib hydrochloride; 150 mg per day, daily until disease progression; Other Names: OSI-774

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patients With Response (Confirmed Complete, and Partial) With Unresectable or Metastatic Malignant Peripheral Nerve Sheath Tumor When Treated With Erlotinib.	Complete response - Complete disappearance of all measurable and non-measurable disease. No new lesions, no disease related symptoms, normalization of markers and other abnormal lab values. Partial response - Greater than or equal to 30% decrease under baseline of the sum of longest diameters of all target measurable lesions. No unequivocal progression of non-measurable disease, no new lesions.	25 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Toxicity	Only adverse events that are possibly, probably or definitely related to study drug are reported.	Up to 25 weeks

Other Outcome Measures

Outcome Measure	Measure Description
Correlate, Preliminarily, Indicators of Epidermal Growth Factor Receptor (EGFR) Function With Response and Progression-free and Overall Survival in Patients Treated With This Drug.	NOT COMPLETED DUE TO EARLY CLOSURE OF STUDY
Feasibility of Accruing These Patients in the Cooperative Group Setting	NOT COMPLETED DUE TO EARLY CLOSURE OF STUDY

Collaborators and Investigators

• Sponsor: Southwest Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Karen H. Albritton, MD, Dana-Farber Cancer Institute; Study Chair: Scott M. Schuetze, MD, PhD, University of Michigan Rogel Cancer Center

Publications and helpful links

General Publications

• Albritton KH, Rankin C, Coffin CM, et al.: Phase II study of erlotinib in metastatic or unresectable malignant peripheral nerve sheath tumors (MPNST). [Abstract] J Clin Oncol 24 (Suppl 18): A-9518, 524s, 2006.

Study record dates

Study Major Dates

• Study Start: December 1, 2003
• Primary Completion (Actual): July 1, 2007
• Study Completion (Actual): August 1, 2009

Study Registration Dates

• First Submitted: September 10, 2003
• First Submitted That Met QC Criteria: September 10, 2003
• First Posted (Estimate): September 11, 2003

Study Record Updates

• Last Update Posted (Actual): November 6, 2017
• Last Update Submitted That Met QC Criteria: October 3, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: adult neurofibrosarcoma; stage IV adult soft tissue sarcoma; recurrent adult soft tissue sarcoma; stage III adult soft tissue sarcoma; stage II adult soft tissue sarcoma
• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neuromuscular Diseases; Neoplasms, Nerve Tissue; Peripheral Nervous System Diseases; Nervous System Neoplasms; Neoplasms, Connective Tissue; Peripheral Nervous System Neoplasms; Neoplasms, Fibrous Tissue; Fibrosarcoma; Neurofibroma; Sarcoma; Nerve Sheath Neoplasms; Neurofibrosarcoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Erlotinib Hydrochloride
• Other Study ID Numbers: CDR0000322023; U10CA032102 (U.S. NIH Grant/Contract); S0330 (Other Identifier: SWOG)