Sorafenib Tosylate in Treating Patients With Desmoid Tumors or Aggressive Fibromatosis

A Phase III, Double Blind, Randomized, Placebo-Controlled Trial of Sorafenib in Desmoid Tumors or Aggressive Fibromatosis (DT/DF)

This randomized phase III trial compares the effects, good and/or bad, of sorafenib tosylate in treating patients with desmoid tumors or aggressive fibromatosis. Sorafenib tosylate may stop the growth of tumor cells by blocking some of the proteins needed for cell growth. [Funding Source - FDA OOPD]

Study Overview

• Status: Completed
• Conditions: Desmoid Fibromatosis
• Intervention / Treatment: Other: Placebo Administration; Other: Laboratory Biomarker Analysis; Drug: Sorafenib Tosylate; Other: Quality-of-Life Assessment

Detailed Description

PRIMARY OBJECTIVES:

I. To compare the progression-free survival (PFS) rates of patients with desmoid tumors (DT)/deep fibromatosis (DF) who receive either sorafenib (sorafenib tosylate) or placebo using a double-blinded randomized phase III study.

SECONDARY OBJECTIVES:

I. To assess toxicity. II. To assess time to surgical intervention. III. To assess tumor response rates and survival.

TERTIARY OBJECTIVES:

I. To evaluate changes in magnetic resonance imaging (MRI) Tesla (T)2 to predict (or correlate) with a biological effect such as tumor growth (by Response Evaluation Criteria in Solid Tumors [RECIST] version [v]1.1), and pain palliation. (Correlative companion study) II. The mechanism of action of sorafenib in DT/DF remains unknown. In patients consenting to undergo the paired tumor biopsies (A091105-ST1), treatment induced changes will be quantified by histology, gene expression profiling, proteomic changes and selected interrogation of key pathways by western blot and reverse transcription-polymerase chain reaction (RT-PCR). (Correlative companion study) III. To collect archival tissue, baseline (tumor, blood) and day 8 (tumor, blood) specimens for basic science research (A091105-ST1). (Correlative companion study) IV. To assess patient-reported adverse events and quality of life (QOL) as measured by the Patient-Reported Outcomes-Common Terminology Criteria for Adverse Events (PRO-CTCAE) and the single-item overall Linear Analogue Self-Assessment (LASA) (A091105-HO1). (Correlative companion study) V. To assess pain palliation measured by the "worst pain" item of the Brief Pain Inventory Short Form (A091105-HO1). (Correlative companion study)

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive sorafenib tosylate orally (PO) once daily (QD) on days 1-28.

ARM II: Patients receive placebo PO QD on days 1-28. Patients may crossover to Arm I upon disease progression.

In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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

• Study Type: Interventional
• Enrollment (Actual): 87
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • University Health Network-Princess Margaret Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham Cancer Center
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences
  • California
    • Arroyo Grande, California, United States, 93420
      • PCR Oncology
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Yale University
  • Delaware
    • Lewes, Delaware, United States, 19958
      • Beebe Medical Center
    • Newark, Delaware, United States, 19713
      • Helen F Graham Cancer Center
    • Newark, Delaware, United States, 19713
      • Delaware Clinical and Laboratory Physicians PA
    • Newark, Delaware, United States, 19713
      • Medical Oncology Hematology Consultants PA
    • Newark, Delaware, United States, 19718
      • Christiana Care Health System-Christiana Hospital
    • Newark, Delaware, United States, 19713
      • Christiana Gynecologic Oncology LLC
    • Rehoboth Beach, Delaware, United States, 19971
      • Beebe Health Campus
    • Seaford, Delaware, United States, 19973
      • TidalHealth Nanticoke / Allen Cancer Center
    • Wilmington, Delaware, United States, 19801
      • Christiana Care Health System-Wilmington Hospital
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • MedStar Washington Hospital Center
    • Washington, District of Columbia, United States, 20007
      • MedStar Georgetown University Hospital
    • Washington, District of Columbia, United States, 20016
      • Sibley Memorial Hospital
  • Florida
    • Jacksonville, Florida, United States, 32224-9980
      • Mayo Clinic in Florida
  • Georgia
    • Columbus, Georgia, United States, 31904
      • John B Amos Cancer Center
    • Savannah, Georgia, United States, 31405
      • Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
    • Savannah, Georgia, United States, 31404
      • Low Country Cancer Care
  • Hawaii
    • 'Aiea, Hawaii, United States, 96701
      • Pali Momi Medical Center
    • 'Aiea, Hawaii, United States, 96701
      • Queen's Cancer Center - Pearlridge
    • Honolulu, Hawaii, United States, 96813
      • Queen's Medical Center
    • Honolulu, Hawaii, United States, 96813
      • Hawaii Cancer Care Inc - Waterfront Plaza
    • Honolulu, Hawaii, United States, 96813
      • Straub Clinic and Hospital
    • Honolulu, Hawaii, United States, 96813
      • University of Hawaii Cancer Center
    • Honolulu, Hawaii, United States, 96817
      • Hawaii Cancer Care Inc-Liliha
    • Honolulu, Hawaii, United States, 96817
      • Kuakini Medical Center
    • Honolulu, Hawaii, United States, 96817
      • Queen's Cancer Center - Kuakini
    • Honolulu, Hawaii, United States, 96826
      • Kapiolani Medical Center for Women and Children
    • Lihue, Hawaii, United States, 96766
      • Wilcox Memorial Hospital and Kauai Medical Clinic
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
    • Mount Vernon, Illinois, United States, 62864
      • Good Samaritan Regional Health Center
  • Indiana
    • Richmond, Indiana, United States, 47374
      • Reid Health
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa/Holden Comprehensive Cancer Center
    • Sioux City, Iowa, United States, 51101
      • Siouxland Regional Cancer Center
  • Kentucky
    • Crestview Hills, Kentucky, United States, 41017
      • Oncology Hematology Care Inc-Crestview
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University/Sidney Kimmel Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan Comprehensive Cancer Center
  • Minnesota
    • Burnsville, Minnesota, United States, 55337
      • Fairview Ridges Hospital
    • Coon Rapids, Minnesota, United States, 55433
      • Mercy Hospital
    • Edina, Minnesota, United States, 55435
      • Fairview Southdale Hospital
    • Fridley, Minnesota, United States, 55432
      • Unity Hospital
    • Hutchinson, Minnesota, United States, 55350
      • Hutchinson Area Health Care
    • Maplewood, Minnesota, United States, 55109
      • Saint John's Hospital - Healtheast
    • Maplewood, Minnesota, United States, 55109
      • Minnesota Oncology Hematology PA-Maplewood
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center
    • Minneapolis, Minnesota, United States, 55407
      • Abbott-Northwestern Hospital
    • Minneapolis, Minnesota, United States, 55454
      • Health Partners Inc
    • New Ulm, Minnesota, United States, 56073
      • New Ulm Medical Center
    • Robbinsdale, Minnesota, United States, 55422
      • North Memorial Medical Health Center
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester
    • Saint Louis Park, Minnesota, United States, 55416
      • Park Nicollet Clinic - Saint Louis Park
    • Saint Louis Park, Minnesota, United States, 55416
      • Metro Minnesota Community Oncology Research Consortium
    • Saint Paul, Minnesota, United States, 55101
      • Regions Hospital
    • Saint Paul, Minnesota, United States, 55102
      • United Hospital
    • Shakopee, Minnesota, United States, 55379
      • Saint Francis Regional Medical Center
    • Stillwater, Minnesota, United States, 55082
      • Lakeview Hospital
    • Waconia, Minnesota, United States, 55387
      • Ridgeview Medical Center
    • Willmar, Minnesota, United States, 56201
      • Rice Memorial Hospital
    • Woodbury, Minnesota, United States, 55125
      • Minnesota Oncology Hematology PA-Woodbury
  • Missouri
    • Bolivar, Missouri, United States, 65613
      • Central Care Cancer Center - Bolivar
    • Branson, Missouri, United States, 65616
      • Cox Cancer Center Branson
    • Creve Coeur, Missouri, United States, 63141
      • Siteman Cancer Center at West County Hospital
    • Joplin, Missouri, United States, 64804
      • Freeman Health System
    • Joplin, Missouri, United States, 64804
      • Mercy Hospital Joplin
    • Rolla, Missouri, United States, 65401
      • Delbert Day Cancer Institute at PCRMC
    • Rolla, Missouri, United States, 65401
      • Mercy Clinic-Rolla-Cancer and Hematology
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
    • Saint Louis, Missouri, United States, 63141
      • Mercy Hospital Saint Louis
    • Saint Louis, Missouri, United States, 63129
      • Siteman Cancer Center-South County
    • Saint Louis, Missouri, United States, 63109
      • Saint Louis Cancer and Breast Institute-South City
    • Saint Peters, Missouri, United States, 63376
      • Siteman Cancer Center at Saint Peters Hospital
    • Springfield, Missouri, United States, 65807
      • CoxHealth South Hospital
    • Springfield, Missouri, United States, 65804
      • Mercy Hospital Springfield
  • Nebraska
    • Lincoln, Nebraska, United States, 68506
      • Nebraska Hematology and Oncology
    • Lincoln, Nebraska, United States, 68510
      • Nebraska Cancer Research Center
    • Lincoln, Nebraska, United States, 68516
      • Southeast Nebraska Cancer Center - 68th Street Place
    • Norfolk, Nebraska, United States, 68701
      • Faith Regional Health Services Carson Cancer Center
    • North Platte, Nebraska, United States, 69101
      • Great Plains Health Callahan Cancer Center
    • Omaha, Nebraska, United States, 68124
      • Alegent Health Bergan Mercy Medical Center
    • Omaha, Nebraska, United States, 68122
      • Alegent Health Immanuel Medical Center
    • Omaha, Nebraska, United States, 68130
      • Alegent Health Lakeside Hospital
    • Omaha, Nebraska, United States, 68131
      • Creighton University Medical Center
    • Omaha, Nebraska, United States, 68106
      • Missouri Valley Cancer Consortium
    • Omaha, Nebraska, United States, 68124
      • Nebraska Cancer Specialists - Omaha
    • Omaha, Nebraska, United States, 68130
      • Oncology Hematology West PC
    • Scottsbluff, Nebraska, United States, 69361
      • Regional West Medical Center Cancer Center
  • Nevada
    • Henderson, Nevada, United States, 89052
      • Comprehensive Cancer Centers of Nevada - Henderson
    • Henderson, Nevada, United States, 89052
      • Cancer and Blood Specialists-Henderson
    • Henderson, Nevada, United States, 89052
      • Las Vegas Cancer Center-Henderson
    • Henderson, Nevada, United States, 89074
      • Comprehensive Cancer Centers of Nevada-Southeast Henderson
    • Henderson, Nevada, United States, 89074
      • GenesisCare USA - Henderson
    • Las Vegas, Nevada, United States, 89144
      • Summerlin Hospital Medical Center
    • Las Vegas, Nevada, United States, 89106
      • Radiation Oncology Centers of Nevada Central
    • Las Vegas, Nevada, United States, 89109
      • GenesisCare USA - Las Vegas
    • Las Vegas, Nevada, United States, 89119
      • Radiation Oncology Centers of Nevada Southeast
    • Las Vegas, Nevada, United States, 89128
      • Comprehensive Cancer Centers of Nevada - Northwest
    • Las Vegas, Nevada, United States, 89144
      • Comprehensive Cancer Centers of Nevada-Summerlin
    • Las Vegas, Nevada, United States, 89148
      • Comprehensive Cancer Centers of Nevada
    • Las Vegas, Nevada, United States, 89148
      • OptumCare Cancer Care at Fort Apache
    • Las Vegas, Nevada, United States, 89169
      • Comprehensive Cancer Centers of Nevada - Central Valley
    • Las Vegas, Nevada, United States, 89106
      • Cancer and Blood Specialists-Shadow
    • Las Vegas, Nevada, United States, 89109
      • HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway
    • Las Vegas, Nevada, United States, 89113
      • HealthCare Partners Medical Group Oncology/Hematology-San Martin
    • Las Vegas, Nevada, United States, 89121
      • Cancer Therapy and Integrative Medicine
    • Las Vegas, Nevada, United States, 89128
      • Cancer and Blood Specialists-Tenaya
    • Las Vegas, Nevada, United States, 89128
      • GenesisCare USA - Vegas Tenaya
    • Las Vegas, Nevada, United States, 89128
      • HealthCare Partners Medical Group Oncology/Hematology-Tenaya
    • Las Vegas, Nevada, United States, 89148-2405
      • Las Vegas Cancer Center-Medical Center
    • Las Vegas, Nevada, United States, 89148
      • GenesisCare USA - Fort Apache
    • Las Vegas, Nevada, United States, 89149
      • HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills
    • Las Vegas, Nevada, United States, 89169
      • Nevada Cancer Research Foundation NCORP
    • Reno, Nevada, United States, 89503
      • Saint Mary's Regional Medical Center
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10032
      • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Centerville, Ohio, United States, 45459
      • Miami Valley Hospital South
    • Cincinnati, Ohio, United States, 45242
      • Oncology Hematology Care Inc-Blue Ash
    • Cincinnati, Ohio, United States, 45202
      • Oncology Hematology Care Inc-Eden Park
    • Cincinnati, Ohio, United States, 45211
      • Oncology Hematology Care Inc-Mercy West
    • Cincinnati, Ohio, United States, 45230
      • Oncology Hematology Care Inc-Anderson
    • Cincinnati, Ohio, United States, 45236
      • Oncology Hematology Care Inc-Kenwood
    • Dayton, Ohio, United States, 45406
      • Good Samaritan Hospital - Dayton
    • Dayton, Ohio, United States, 45409
      • Miami Valley Hospital
    • Dayton, Ohio, United States, 45415
      • Miami Valley Hospital North
    • Dayton, Ohio, United States, 45459
      • Dayton NCI Community Oncology Research Program
    • Fairfield, Ohio, United States, 45014
      • Oncology Hematology Care Inc-Healthplex
    • Findlay, Ohio, United States, 45840
      • Blanchard Valley Hospital
    • Franklin, Ohio, United States, 45005-1066
      • Atrium Medical Center-Middletown Regional Hospital
    • Greenville, Ohio, United States, 45331
      • Wayne Hospital
    • Kettering, Ohio, United States, 45429
      • Kettering Medical Center
    • Springfield, Ohio, United States, 45505
      • Springfield Regional Medical Center
    • Springfield, Ohio, United States, 45504
      • Springfield Regional Cancer Center
    • Troy, Ohio, United States, 45373
      • Upper Valley Medical Center
    • Wright-Patterson Air Force Base, Ohio, United States, 45433
      • Wright-Patterson Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
    • Tulsa, Oklahoma, United States, 74146
      • Oklahoma Cancer Specialists and Research Institute-Tulsa
  • Pennsylvania
    • Chadds Ford, Pennsylvania, United States, 19317
      • Christiana Care Health System-Concord Health Center
    • Philadelphia, Pennsylvania, United States, 19111
      • Fox Chase Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Institute/University of Utah
  • Virginia
    • Martinsville, Virginia, United States, 24115
      • Sovah Health Martinsville
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin
    • New Richmond, Wisconsin, United States, 54017
      • Cancer Center of Western Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients must have confirmation of DT/DF by local pathologist prior to registration
• Patients may have been treated with locoregional therapies such as major surgery, radiation, radiofrequency ablation, or cryosurgery provided this has been completed at least 4 weeks prior to registration and recovered from therapy related toxicity to less than CTCAE grade 2
• Patients may have been treated with cytotoxic, biologic (antibody), immune or experimental therapy, tyrosine kinase inhibitors, hormone inhibitors or nonsteroidal anti-inflammatory drugs (NSAIDs) provided this has been completed at least 4 weeks prior to registration (6 weeks for mitomycin and nitrosoureas) and recovered from any therapy related toxicity to less than CTCAE grade 2
• Patients with prior or current treatment of sorafenib are excluded

• No concomitant treatment, in therapeutic doses, with anticoagulants such as warfarin or warfarin-related agents, heparin, thrombin or Factor Xa inhibitors, or antiplatelet agents (e.g., clopidogrel); low dose aspirin (=< 81 mg/day), low-dose warfarin (=< 1 mg/day), and prophylactic low molecular weight heparin (LMWH) are permitted; please note that drugs that strongly induce or inhibit cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) or are associated with a risk of torsades are not allowed; chronic concomitant treatment of CYP3A4 inducers is not allowed (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital, and St. John's wort); as part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product; the following drugs are strong inhibitors of CYP3A4 and are not allowed during the treatment with sorafenib:

  • Boceprevir
  • Indinavir
  • Nelfinavir
  • Lopinavir/ritonavir
  • Saquinavir
  • Telaprevir
  • Ritonavir
  • Clarithromycin
  • Conivaptan
  • Itraconazole
  • Ketoconazole
  • Mibefradil
  • Nefazodone
  • Posaconazole
  • Voriconazole

  • Telithromycin

    • Drugs with possible or conditional risk of torsades should be used with caution knowing that sorafenib could prolong the QT interval
• Chronic daily NSAID use as treatment for controlling desmoid tumors is not allowed, and should be stopped >= 3 days prior to registration; NSAIDS are allowed when used for desmoid tumor-related pain or for symptoms that are unrelated to desmoid disease (eg. headache, arthritis)
• Patients must have measurable disease

• Patients have to meet one of the following criteria to be eligible:

  • Disease determined unresectable or entailing unacceptably morbid surgery based on 1 or more of the following characteristics:

    • Multifocal disease
    • Disease in which there is involvement or inadequate plane from: neurovascular bundle, bone, skin, or viscera
    • Large size in relationship to location OR multi-compartment involvement
  • Progression by radiographic imaging (10% increase in size by RECIST v1.1 within 6 months of registration)

  • Patients with symptomatic disease which meets the following criteria Brief Pain Inventory (BPI) score greater than or equal to 3 AND one of the following:

    • Inability to control pain with NSAIDs and considering addition of narcotics OR
    • > 30% increase in current use of narcotics OR
    • Addition of a new opioid narcotic
• Eastern Cooperative Oncology Group (ECOG) performance status =< 2
• Patients who are pregnant or nursing are not eligible
• No patients with a history of cardiac disease: congestive heart failure > class II New York Heart Association (NYHA); active coronary artery disease (CAD) (myocardial infarction or unstable angina within 6 months prior to study entry)
• No patients with inadequately controlled hypertension (defined as a blood pressure of >= 150 mmHg systolic and/or >= 90 mmHg diastolic), or any prior history of hypertensive crisis or hypertensive encephalopathy
• No patients with clinically significant gastrointestinal (GI) bleeding or bleeding diathesis within 30 days prior to registration
• Absolute neutrophil count >= 1,500/mm^3
• Hemoglobin >= 8 g/dl
• Platelets >= 75,000/mm^3
• Total bilirubin =< 1.5 x upper limits of normal (ULN)
• Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST])/serum glutamate pyruvate transaminase (SGPT) (aspartate aminotransferase [ALT]) =< 1.5 x ULN
• Calculated creatinine clearance >= 50 mL/min using the Cockcroft-Gault equation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (sorafenib tosylate); Patients receive sorafenib tosylate PO QD on days 1-28.	Other: Laboratory Biomarker Analysis; Optional correlative studies; Drug: Sorafenib Tosylate; Given PO; Other Names: BAY 54-9085; Nexavar; BAY 43-9006 Tosylate; sorafenib; Other: Quality-of-Life Assessment; Optional ancillary studies; Other Names: Quality of Life Assessment
Placebo Comparator: Arm II (placebo); Patients receive placebo PO QD on days 1-28. Patients may crossover to Arm I upon disease progression.	Other: Placebo Administration; Given PO; Other: Laboratory Biomarker Analysis; Optional correlative studies; Other: Quality-of-Life Assessment; Optional ancillary studies; Other Names: Quality of Life Assessment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival(PFS) Rate	PFS is defined as the time from randomization to the first occurrence of progression or death due to any cause. If no event exists, the PFS will be censored at the last disease assessment. Data following cross over will be analyzed and summarized separately from the data from the main course of treatment for these patients in an exploratory and hypothesis generating manner. Intention to treat principles will be used. Patient disease status was evaluated using RECSIT v1.1. Patients ending treatment for symptomatic deterioration without radiographic evidence of PD, were classified as having PD. Otherwise, patients not yet showing disease progression were classified as having no progression at the most recent disease assessment and in the following cases: crossing over to receive sorafenib, date of first non-protocol directed anti-cancer therapy, lost to follow-up, withdrawal of consent, and changing imaging methods from that which was used at study entry.	Time from randomization to the first occurrence of progression or death due to any cause, assessed up to 3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Adverse Events, Using the Patient Reported Outcomes-Common Terminology Criteria in Adverse Events Version 4.0	INCLUDED IN THE ADVERSE EVENTS PORTION OF THE RESULTS SECTION. Frequency tables, summary statistics, and categorical analysis will be used to compare the distributions of toxicity for patients treated with sorafenib tosylate vs placebo. Data for patients who have crossed over or having received surgical or radiotherapy intervention will be summarized independently from their primary course of study treatment in an exploratory and hypothesis generating manner.	Up to 3 years
Time to Surgical Intervention During Treatment	A log rank test will be used to compare the distributions of time to surgical intervention between the two arms using a 2-sided test and alpha=0.05 level of significance. Kaplan-Meier methodology will be used to estimate various time points and 95% confidence intervals will be calculated for these estimates. Surgery will be classified by outcome (eg, complete-macroscopic, complete-microscopic, or partial), type, location (eg, limb), thereafter analyzed by categorical analysis and descriptive statistics. Non-parametric methods will be used, as appropriate. Too few patients had surgery during treatment to perform analysis.	Time between randomization to the patient undergoing therapeutic surgical resection for this disease, assessed up to 3 years
Overall Survival	Kaplan-Meier methodology and log rank tests will be used to compare overall survival between the groups at various time points (eg, 1 year rate, 2 year rate, etc) and 95% confidence intervals will be calculated for these estimates. Data following crossover will be analyzed and summarized separately from the main course of treatment for these patients in an exploratory and hypothesis generating manner.	Time between the date of randomization to until death, assessed up to 3 years
Best Objective Status Between the Two Treatment Arms According to Response Evaluation Criteria in Solid Tumors Version 1.1	Compared between the two treatment arms and using the Cochran-Mantel-Haenszel test. Complete Response (CR): All of the following must be true: a. Disappearance of all target lesions. b. Each target lymph node must have reduction in short axis to <1.0 cm. Partial Response (PR): At least a 30% decrease in PBSD (sum of the longest diameter for all target lesions plus the sum of the short axis of all the target lymph nodes at current evaluation) taking as reference the BSD. Patients on Arm II (placebo) who crossover are censored for Best Objective Status at the time of crossover.	Up to 3 years
Duration of Response	Kaplan Meier methodology will be used to estimate the distribution of duration of response and the log-rank test will be used to test for a difference in duration of response between the two arms. Patients on Arm II (placebo) who crossover are censored for Duration of Response at the time of crossover.	Time between first tumor response and progression, assessed up to 3 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in Tumor Size by Response Evaluation Criteria in Solid Tumors Version 1.1 (Correlative Companion Study-Imaging Study)	Best response (ordinal variable) and percent T2 signal change (continuous) will be correlated by Spearman?s rho.	Baseline up to 3 years
Percent Changes in MRI T2 Signal (Correlative Companion Study-Imaging Study)	Percent T2 signal change (continuous) will be correlated by Spearman?s rho. The percent changes in MRI T2 signal from Week 8 to subsequent imaging will be compared between groups with > 30% pain palliation using t-test or a nonparametric alternative (e.g., Wilcoxon rank-sum test).	Baseline up to 3 years
Time to Pain Progression Measured by the ?Worst Pain? Item of the Brief Pain Inventory Short Form (Correlative Companion Study- A091105-H01 QOL Study)	Defined as a >= 30% increase compared with baseline in the worst pain intensity score (BPI-SF ?worst pain? item) or either a >= 30% increase in the average daily use of any type of opioid narcotic or the addition of a new opioid narcotic compared with baseline. Estimated for each arm using Kaplan-Meier estimates and will be compared between arms using a log- rank test. Descriptive statistics will include means, standard deviations, medians, and ranges for each continuous or ordinal scale/subscale/item by group at each time point.	Date of randomization to the earliest date that pain progression is observed, assessed up to 12 weeks
Time to Pain Palliation Measured by the ?Worst Pain? Item of the Brief Pain Inventory Short Form (Correlative Companion Study-A091105-H01 QOL Study)	Defined at each time point as >= 30% decrease from baseline in the worst pain intensity score (BPI-SF ?worst pain? item), with neither a concomitant >= 30% increase in average daily use of any opioid narcotic, nor addition of any new opioid narcotic, relative to baseline. Estimated for each arm using Kaplan-Meier estimates and will be compared between arms using a log- rank test. Descriptive statistics will include means, standard deviations, medians, and ranges for each continuous or ordinal scale/subscale/item by group at each time point.	Date of randomization to the earliest date that confirmed pain palliation is observed, assessed up to 12 weeks
Duration of Pain Palliation Measured by the ?Worst Pain? Item of the Brief Pain Inventory Short Form (Correlative Companion Study- A091105-H01 QOL Study)	Defined for all patients who experience confirmed pain palliation. Descriptive statistics will include means, standard deviations, medians, and ranges for each continuous or ordinal scale/subscale/item by group at each time point. Descriptive graphical techniques will include mean plots by group for each continuous or ordinal scale/subscale/item. Relative frequencies of responses for each ordinal item will also be generated at each time point by group.	Time from the earliest date that confirmed pain palliation is observed to the earliest date that pain progression is observed, assessed up to 12 weeks
Rate of Pain Palliation Measured by the ?Worst Pain? Item of the Brief Pain Inventory Short Form (Correlative Companion Study-A091105-H01 QOL Study)	Rate of pain palliation at week 8 confirmed as week 12 will be compared between arms using a two-sided alpha=0.05 chi-squared tests at the time of the final analysis. Descriptive statistics will include means, standard deviations, medians, and ranges for each continuous or ordinal scale/subscale/item by group at each time point. Descriptive graphical techniques will include mean plots by group for each continuous or ordinal scale/subscale/item. Relative frequencies of responses for each ordinal item will also be generated at each time point by group.	Baseline up to 12 weeks
Cadherin-associated Protein, Beta 1 (CTNNB1) Genotype (Correlative Companion Study-A091105-ST1 Study)	Associations among the possible predictors of response to sorafenib and CTNNBI mutations will be examined using Fisher?s exact test, Kruskal-Wallis test, or Spearman?s correlation coefficient as appropriate. Strata will be compared by using the log-rank test. Multivariate models will be constructed by introducing all variables aforementioned simultaneously into the model and then eliminating variables using the backward selection method. P values will be two-tailed and considered significant at alpha 0.05.	Up to 3 years
False Discovery Rate (Correlative Companion Study- A091105-ST1 Study)	Permutation testing of the same selection will be performed 1000 times and the sample group labels switched around in each permutation. A two-sided t-test will be used to identify differentially expressed genes on log transformed data and those with a twofold change. False discovery rate will be assessed by permutation testing (n = 1000) of the sample group labels. Enrichment will be assessed by one-sided Fisher?s exact test with estimated false discovery rate.	Up to day 8
Treatment-specific Gene Expression Signature (Correlative Companion Study- A091105-ST1 Study)	The analysis will identify over- and under-expressed genes in pre-treatment and day 8 biopsies as compared to all control samples.	Up to day 8
Changes in Immunohistochemistry Score of Vascular Endothelial Growth Factor (Correlative Companion Study- A091105-ST1 Study)	Compared by paired t-test. Quantitative changes will be correlated with disease status at 1 year by Fishers exact test.	Baseline up to day 8
Changes in Immunohistochemistry Score of Platelet-derived Growth Factor Receptor (Correlative Companion Study- A091105-ST1 Study)	Compared by paired t-test. Quantitative changes will be correlated with disease status at 1 year by Fishers exact test.	Baseline up to day 8
Changes in Immunohistochemistry Score of Beta-catenin Cytoplasm/Nuclear Ratio (Correlative Companion Study- A091105-ST1 Study)	Compared by paired t-test. Quantitative changes will be correlated with disease status at 1 year by Fishers exact test.	Baseline up to day 8

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Mrinal M Gounder, Alliance for Clinical Trials in Oncology

Publications and helpful links

General Publications

• Mazza GL, Petersen MM, Ginos B, Langlais BT, Heon N, Gounder MM, Mahoney MR, Zoroufy AJ, Schwartz GK, Rogak LJ, Thanarajasingam G, Basch E, Dueck AC. Missing data strategies for the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) in Alliance A091105 and COMET-2. Qual Life Res. 2022 Apr;31(4):1069-1080. doi: 10.1007/s11136-021-02968-1. Epub 2021 Aug 21. Erratum In: Qual Life Res. 2021 Oct 11;:
• Basch E, Becker C, Rogak LJ, Schrag D, Reeve BB, Spears P, Smith ML, Gounder MM, Mahoney MR, Schwartz GK, Bennett AV, Mendoza TR, Cleeland CS, Sloan JA, Bruner DW, Schwab G, Atkinson TM, Thanarajasingam G, Bertagnolli MM, Dueck AC. Composite grading algorithm for the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). Clin Trials. 2021 Feb;18(1):104-114. doi: 10.1177/1740774520975120. Epub 2020 Dec 1.
• Gounder MM, Mahoney MR, Van Tine BA, Ravi V, Attia S, Deshpande HA, Gupta AA, Milhem MM, Conry RM, Movva S, Pishvaian MJ, Riedel RF, Sabagh T, Tap WD, Horvat N, Basch E, Schwartz LH, Maki RG, Agaram NP, Lefkowitz RA, Mazaheri Y, Yamashita R, Wright JJ, Dueck AC, Schwartz GK. Sorafenib for Advanced and Refractory Desmoid Tumors. N Engl J Med. 2018 Dec 20;379(25):2417-2428. doi: 10.1056/NEJMoa1805052.

Helpful Links

• Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive.

Study record dates

Study Major Dates

• Study Start (Actual): March 21, 2014
• Primary Completion (Actual): July 3, 2019
• Study Completion (Actual): December 1, 2022

Study Registration Dates

• First Submitted: February 17, 2014
• First Submitted That Met QC Criteria: February 17, 2014
• First Posted (Estimated): February 19, 2014

Study Record Updates

• Last Update Posted (Actual): June 7, 2023
• Last Update Submitted That Met QC Criteria: June 6, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Connective Tissue; Neoplasms, Fibrous Tissue; Fibromatosis, Aggressive; Fibroma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Sorafenib
• Other Study ID Numbers: NCI-2014-00264 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); U10CA180821 (U.S. NIH Grant/Contract); U10CA031946 (U.S. NIH Grant/Contract); PA091105_A04PAMDREVW01; A091105 (Other Identifier: CTEP); R01FD005105 (U.S. FDA Grant/Contract)