Desmoid FibromatosisPhase 3NCT02066181
Sorafenib Tosylate in Treating Patients With Desmoid Tumors or Aggressive Fibromatosis
A Phase 3 study testing Laboratory Biomarker Analysis, Quality-of-Life Assessment and Sorafenib Tosylate in people with Desmoid Fibromatosis, run by National Cancer Institute (NCI) at 150 sites in 2 countries.
Trial summary
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] Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Desmoid Fibromatosis
- What is being tested?
- Laboratory Biomarker Analysis, Quality-of-Life Assessment and Sorafenib Tosylate
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 87 participants
- Where
- 150 sitesin 2 countries
- Study dates
- 21 Mar 2014to 1 Dec 2022
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 45Show fewer
- 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
Who cannot join
None listed.
Trial locations and contacts
150 sites in 2 countries.
150 sites in 2 countries
United States149 sites
Pali Momi Medical Center
‘Aiea, Hawaii, 96701
Queen's Cancer Center - Pearlridge
‘Aiea, Hawaii, 96701
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109
PCR Oncology
Arroyo Grande, California, 93420
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, 35233
Central Care Cancer Center - Bolivar
Bolivar, Missouri, 65613
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Cox Cancer Center Branson
Branson, Missouri, 65616
Fairview Ridges Hospital
Burnsville, Minnesota, 55337
Miami Valley Hospital South
Centerville, Ohio, 45459
Christiana Care Health System-Concord Health Center
Chadds Ford, Pennsylvania, 19317
Northwestern University
Chicago, Illinois, 60611
Oncology Hematology Care Inc-Eden Park
Cincinnati, Ohio, 45202
Oncology Hematology Care Inc-Mercy West
Cincinnati, Ohio, 45211
Oncology Hematology Care Inc-Anderson
Cincinnati, Ohio, 45230
Oncology Hematology Care Inc-Kenwood
Cincinnati, Ohio, 45236
Oncology Hematology Care Inc-Blue Ash
Cincinnati, Ohio, 45242
Siteman Cancer Center at Saint Peters Hospital
City of Saint Peters, Missouri, 63376
John B Amos Cancer Center
Columbus, Georgia, 31904
Mercy Hospital
Coon Rapids, Minnesota, 55433
Oncology Hematology Care Inc-Crestview
Crestview Hills, Kentucky, 41017
Siteman Cancer Center at West County Hospital
Creve Coeur, Missouri, 63141
Good Samaritan Hospital - Dayton
Dayton, Ohio, 45406
Miami Valley Hospital
Dayton, Ohio, 45409
Miami Valley Hospital North
Dayton, Ohio, 45415
Dayton NCI Community Oncology Research Program
Dayton, Ohio, 45459
Duke University Medical Center
Durham, North Carolina, 27710
Fairview Southdale Hospital
Edina, Minnesota, 55435
Oncology Hematology Care Inc-Healthplex
Fairfield, Ohio, 45014
Blanchard Valley Hospital
Findlay, Ohio, 45840
Atrium Medical Center-Middletown Regional Hospital
Franklin, Ohio, 45005-1066
Unity Hospital
Fridley, Minnesota, 55432
Wayne Hospital
Greenville, Ohio, 45331
Hackensack University Medical Center
Hackensack, New Jersey, 07601
Cancer and Blood Specialists-Henderson
Henderson, Nevada, 89052
Comprehensive Cancer Centers of Nevada - Henderson
Henderson, Nevada, 89052
Las Vegas Cancer Center-Henderson
Henderson, Nevada, 89052
Comprehensive Cancer Centers of Nevada-Southeast Henderson
Henderson, Nevada, 89074
GenesisCare USA - Henderson
Henderson, Nevada, 89074
Hawaii Cancer Care Inc - Waterfront Plaza
Honolulu, Hawaii, 96813
Queen's Medical Center
Honolulu, Hawaii, 96813
Straub Clinic and Hospital
Honolulu, Hawaii, 96813
University of Hawaii Cancer Center
Honolulu, Hawaii, 96813
Hawaii Cancer Care Inc-Liliha
Honolulu, Hawaii, 96817
Kuakini Medical Center
Honolulu, Hawaii, 96817
Queen's Cancer Center - Kuakini
Honolulu, Hawaii, 96817
Kapiolani Medical Center for Women and Children
Honolulu, Hawaii, 96826
M D Anderson Cancer Center
Houston, Texas, 77030
Hutchinson Area Health Care
Hutchinson, Minnesota, 55350
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242
Mayo Clinic in Florida
Jacksonville, Florida, 32224-9980
Freeman Health System
Joplin, Missouri, 64804
Mercy Hospital Joplin
Joplin, Missouri, 64804
Kettering Medical Center
Kettering, Ohio, 45429
Cancer and Blood Specialists-Shadow
Las Vegas, Nevada, 89106
Radiation Oncology Centers of Nevada Central
Las Vegas, Nevada, 89106
GenesisCare USA - Las Vegas
Las Vegas, Nevada, 89109
HealthCare Partners Medical Group Oncology/Hematology-Maryland Parkway
Las Vegas, Nevada, 89109
HealthCare Partners Medical Group Oncology/Hematology-San Martin
Las Vegas, Nevada, 89113
Radiation Oncology Centers of Nevada Southeast
Las Vegas, Nevada, 89119
Cancer Therapy and Integrative Medicine
Las Vegas, Nevada, 89121
Cancer and Blood Specialists-Tenaya
Las Vegas, Nevada, 89128
Comprehensive Cancer Centers of Nevada - Northwest
Las Vegas, Nevada, 89128
GenesisCare USA - Vegas Tenaya
Las Vegas, Nevada, 89128
HealthCare Partners Medical Group Oncology/Hematology-Tenaya
Las Vegas, Nevada, 89128
Comprehensive Cancer Centers of Nevada-Summerlin
Las Vegas, Nevada, 89144
Summerlin Hospital Medical Center
Las Vegas, Nevada, 89144
Las Vegas Cancer Center-Medical Center
Las Vegas, Nevada, 89148-2405
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, 89148
GenesisCare USA - Fort Apache
Las Vegas, Nevada, 89148
OptumCare Cancer Care at Fort Apache
Las Vegas, Nevada, 89148
HealthCare Partners Medical Group Oncology/Hematology-Centennial Hills
Las Vegas, Nevada, 89149
Comprehensive Cancer Centers of Nevada - Central Valley
Las Vegas, Nevada, 89169
Nevada Cancer Research Foundation NCORP
Las Vegas, Nevada, 89169
Beebe Medical Center
Lewes, Delaware, 19958
Wilcox Memorial Hospital and Kauai Medical Clinic
Lihue, Hawaii, 96766
Nebraska Hematology and Oncology
Lincoln, Nebraska, 68506
Nebraska Cancer Research Center
Lincoln, Nebraska, 68510
Southeast Nebraska Cancer Center - 68th Street Place
Lincoln, Nebraska, 68516
University of Arkansas for Medical Sciences
Little Rock, Arkansas, 72205
Minnesota Oncology Hematology PA-Maplewood
Maplewood, Minnesota, 55109
Saint John's Hospital - Healtheast
Maplewood, Minnesota, 55109
Sovah Health Martinsville
Martinsville, Virginia, 24115
Loyola University Medical Center
Maywood, Illinois, 60153
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Abbott-Northwestern Hospital
Minneapolis, Minnesota, 55407
Hennepin County Medical Center
Minneapolis, Minnesota, 55415
Health Partners Inc
Minneapolis, Minnesota, 55454
Good Samaritan Regional Health Center
Mount Vernon, Illinois, 62864
Yale University
New Haven, Connecticut, 06520
Cancer Center of Western Wisconsin
New Richmond, Wisconsin, 54017
New Ulm Medical Center
New Ulm, Minnesota, 56073
NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center
New York, New York, 10032
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Christiana Gynecologic Oncology LLC
Newark, Delaware, 19713
Delaware Clinical and Laboratory Physicians PA
Newark, Delaware, 19713
Helen F Graham Cancer Center
Newark, Delaware, 19713
Medical Oncology Hematology Consultants PA
Newark, Delaware, 19713
Christiana Care Health System-Christiana Hospital
Newark, Delaware, 19718
Faith Regional Health Services Carson Cancer Center
Norfolk, Nebraska, 68701
Great Plains Health Callahan Cancer Center
North Platte, Nebraska, 69101
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104
Missouri Valley Cancer Consortium
Omaha, Nebraska, 68106
Alegent Health Immanuel Medical Center
Omaha, Nebraska, 68122
Alegent Health Bergan Mercy Medical Center
Omaha, Nebraska, 68124
Nebraska Cancer Specialists - Omaha
Omaha, Nebraska, 68124
Alegent Health Lakeside Hospital
Omaha, Nebraska, 68130
Oncology Hematology West PC
Omaha, Nebraska, 68130
Creighton University Medical Center
Omaha, Nebraska, 68131
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111
Beebe Health Campus
Rehoboth Beach, Delaware, 19971
Saint Mary's Regional Medical Center
Reno, Nevada, 89503
Reid Health
Richmond, Indiana, 47374
North Memorial Medical Health Center
Robbinsdale, Minnesota, 55422
Mayo Clinic in Rochester
Rochester, Minnesota, 55905
Delbert Day Cancer Institute at PCRMC
Rolla, Missouri, 65401
Mercy Clinic-Rolla-Cancer and Hematology
Rolla, Missouri, 65401
Metro Minnesota Community Oncology Research Consortium
Saint Louis Park, Minnesota, 55416
Park Nicollet Clinic - Saint Louis Park
Saint Louis Park, Minnesota, 55416
Regions Hospital
Saint Paul, Minnesota, 55101
United Hospital
Saint Paul, Minnesota, 55102
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112
Low Country Cancer Care
Savannah, Georgia, 31404
Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
Savannah, Georgia, 31405
Regional West Medical Center Cancer Center
Scottsbluff, Nebraska, 69361
TidalHealth Nanticoke / Allen Cancer Center
Seaford, Delaware, 19973
Saint Francis Regional Medical Center
Shakopee, Minnesota, 55379
Siouxland Regional Cancer Center
Sioux City, Iowa, 51101
Mercy Hospital Springfield
Springfield, Missouri, 65804
CoxHealth South Hospital
Springfield, Missouri, 65807
Springfield Regional Cancer Center
Springfield, Ohio, 45504
Springfield Regional Medical Center
Springfield, Ohio, 45505
Saint Louis Cancer and Breast Institute-South City
St Louis, Missouri, 63109
Washington University School of Medicine
St Louis, Missouri, 63110
Siteman Cancer Center-South County
St Louis, Missouri, 63129
Mercy Hospital Saint Louis
St Louis, Missouri, 63141
Lakeview Hospital
Stillwater, Minnesota, 55082
Upper Valley Medical Center
Troy, Ohio, 45373
Oklahoma Cancer Specialists and Research Institute-Tulsa
Tulsa, Oklahoma, 74146
Ridgeview Medical Center
Waconia, Minnesota, 55387
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, 20007
MedStar Washington Hospital Center
Washington D.C., District of Columbia, 20010
Sibley Memorial Hospital
Washington D.C., District of Columbia, 20016
Rice Memorial Hospital
Willmar, Minnesota, 56201
Christiana Care Health System-Wilmington Hospital
Wilmington, Delaware, 19801
Minnesota Oncology Hematology PA-Woodbury
Woodbury, Minnesota, 55125
Wright-Patterson Medical Center
Wright-Patterson Air Force Base, Ohio, 45433
Canada1 site
University Health Network-Princess Margaret Hospital
Toronto, Ontario, M5G 2M9
About this study
Official title: 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]
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- To assess toxicity. II. To assess time to surgical intervention. III. To assess tumor response rates and survival.
TERTIARY OBJECTIVES:
- 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.
- Conditions
- Desmoid Fibromatosis
- Being tested
- Laboratory Biomarker Analysis, Placebo Administration, Quality-of-Life Assessment, Sorafenib Tosylate
- Medical subject headings
- Desmoid Tumors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Laboratory Biomarker AnalysisOther
Optional correlative studies
Placebo AdministrationOther
Given PO
Quality-of-Life AssessmentOther
Also called Quality of Life Assessment
Optional ancillary studies
Sorafenib TosylateDrug
Also called BAY 43-9006 Tosylate, BAY 54-9085, Nexavar, sorafenib
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Arm I (sorafenib tosylate) | Experimental | Patients receive sorafenib tosylate PO QD on days 1-28. Receives: Other: Laboratory Biomarker Analysis; Other: Quality-of-Life Assessment; Drug: Sorafenib Tosylate |
| Arm II (placebo) | Placebo comparator | Patients receive placebo PO QD on days 1-28. Patients may crossover to Arm I upon disease progression. Receives: Other: Laboratory Biomarker Analysis; Other: Placebo Administration; Other: Quality-of-Life Assessment |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Time from randomization to the first occurrence of progression or death due to any cause, assessed up to 3 years
Secondary outcomes (5)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Time between first tumor response and progression, assessed up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2014 (estimated)
- Study start21 Mar 2014
- Primary completion3 Jul 2019
- Study completion1 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Desmoid FibromatosisStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 87 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Mrinal M Gounder, Principal investigator, Alliance for Clinical Trials in Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02066181
- Sponsor's protocol ID
- NCI-2014-00264
- Other IDs
- NCI-2014-00264, PA091105_A04PAMDREVW01, A091105, A091105, A091105, R01FD005105, U10CA180821, U10CA031946
- Status last verified
- May 2026
- First submitted
- 17 Feb 2014
- Last updated
- 24 Jun 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
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.
PubMed 34420143Basch 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.
PubMed 33258687Gounder 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.
PubMed 30575484
Study at a glance
From the registry record, last updated by the sponsor on 24 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase III, Double Blind, Randomized, Placebo-Controlled Trial of Sorafenib in Desmoid Tumors or Aggressive Fibromatosis (DT/DF)
- ClinicalTrials.gov ID
- NCT02066181
- Acronym / sponsor ID
- NCI-2014-00264
- Conditions
- Desmoid Fibromatosis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 87 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 21 Mar 2014 (actual)
- Primary completion
- 3 Jul 2019 (actual)
- Study completion
- 1 Dec 2022 (actual)
- First posted
- 19 Feb 2014 (estimated)
- Results
- Posted 20 Sep 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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]
Detailed description
PRIMARY OBJECTIVES:
- 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:
- To assess toxicity. II. To assess time to surgical intervention. III. To assess tumor response rates and survival.
TERTIARY OBJECTIVES:
- 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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I (sorafenib tosylate) | Experimental | Other: Laboratory Biomarker Analysis, Other: Quality-of-Life Assessment, Drug: Sorafenib TosylatePatients receive sorafenib tosylate PO QD on days 1-28. |
| Arm II (placebo) | Placebo comparator | Other: Laboratory Biomarker Analysis, Other: Placebo Administration, Other: Quality-of-Life AssessmentPatients receive placebo PO QD on days 1-28. Patients may crossover to Arm I upon disease progression. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (45 listed)
- 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:
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Laboratory Biomarker AnalysisOptional correlative studies | Other | Arm I (sorafenib tosylate), Arm II (placebo) |
| Placebo AdministrationGiven PO | Other | Arm II (placebo) |
| Quality-of-Life AssessmentAlso: Quality of Life AssessmentOptional ancillary studies | Other | Arm I (sorafenib tosylate), Arm II (placebo) |
| Sorafenib TosylateAlso: BAY 43-9006 Tosylate, BAY 54-9085, Nexavar, sorafenibGiven PO | Drug | Arm I (sorafenib tosylate) |
Primary outcome
Progression-free Survival(PFS) Rate
Time frame: Time from randomization to the first occurrence of progression or death due to any cause, assessed up to 3 years
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.
5 secondary outcomes
Incidence of Adverse Events, Using the Patient Reported Outcomes-Common Terminology Criteria in Adverse Events Version 4.0
Time frame: Up to 3 years
Time to Surgical Intervention During Treatment
Time frame: Time between randomization to the patient undergoing therapeutic surgical resection for this disease, assessed up to 3 years
Overall Survival
Time frame: 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
Time frame: Up to 3 years
Duration of Response
Time frame: Time between first tumor response and progression, assessed up to 3 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Jun 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34420143Mazza 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.
- Derived from this study: PubMed 33258687Basch 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.
- Derived from this study: PubMed 30575484Gounder 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.
- Data Available: Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive.Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mrinal M Gounder principal investigator
Alliance for Clinical Trials in Oncology
150 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Laboratory Biomarker Analysis, Quality-of-Life Assessment and Sorafenib Tosylate in people with Desmoid Fibromatosis, run by National Cancer Institute (NCI) at 150 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 45 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 150 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Sep 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression-free Survival(PFS) Rate (time frame: Time from randomization to the first occurrence of progression or death due to any cause, assessed up to 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02066181, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jun 2026.