NCT02066181

Sorafenib Tosylate in Treating Patients With Desmoid Tumors or Aggressive Fibromatosis

Completed Phase 3 Results posted Last updated 7 June 2023

What this trial tests

Phase 3 trial testing Laboratory Biomarker Analysis in Desmoid Fibromatosis in 87 participants. Completed in 1 December 2022.

Timeline

21 March 2014

Primary endpoint
3 July 2019

1 December 2022

Quick facts

Lead sponsor	National Cancer Institute (NCI)
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	crossover
Masking	double
Primary purpose	treatment
Enrollment	87
Start date	21 March 2014
Primary completion	3 July 2019
Estimated completion	1 December 2022
Sites	150 locations across Canada, United States

Drugs / interventions tested

• Laboratory Biomarker Analysis — full drug profile →
• Placebo Administration — full drug profile →
• Quality-of-Life Assessment
• Sorafenib Tosylate — full drug profile →

Conditions studied

• Desmoid Fibromatosis — all drugs for Desmoid Fibromatosis →

Sponsor

National Cancer Institute (NCI)

Who can join

18 and older, any sex, with Desmoid Fibromatosis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Progression-free Survival(PFS) Rate Primary · 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.

Group	Value	95% CI
Arm I (Sorafenib Tosylate)	7
Arm II (Placebo)	22
Arm I (Sorafenib Tosylate)	42
Arm II (Placebo)	13

Incidence of Adverse Events, Using the Patient Reported Outcomes-Common Terminology Criteria in Adverse Events Version 4.0 Secondary · Up to 3 years

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.

Group	Value	95% CI
Arm I (Sorafenib Tosylate)	49
Arm II (Placebo)	36
Crossover Patients	0

Time to Surgical Intervention During Treatment Secondary · Time between randomization to the patient undergoing therapeutic surgical resection for this disease, assessed up to 3 years

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 tr

Group	Value	95% CI
Arm I (Sorafenib Tosylate)	1
Arm II (Placebo)	1
Crossover Patients	0
Arm I (Sorafenib Tosylate)	48
Arm II (Placebo)	35
Crossover Patients	0

Overall Survival Secondary · Time between the date of randomization to until death, assessed up to 3 years

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.

Group	Value	95% CI
Arm I (Sorafenib Tosylate)	1
Arm II (Placebo)	0
Crossover Patients	0
Arm I (Sorafenib Tosylate)	48
Arm II (Placebo)	35
Crossover Patients	0

Best Objective Status Between the Two Treatment Arms According to Response Evaluation Criteria in Solid Tumors Version 1.1 Secondary · Up to 3 years

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.

Group	Value	95% CI
Arm I (Sorafenib Tosylate)	1
Arm II (Placebo)	0
Arm I (Sorafenib Tosylate)	15
Arm II (Placebo)	7
Arm I (Sorafenib Tosylate)	33
Arm II (Placebo)	28

Duration of Response Secondary · Time between first tumor response and progression, assessed up to 3 years

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.

Group	Value	95% CI
Arm I (Sorafenib Tosylate)	14.7	8.7 – 18.6
Arm II (Placebo)	11.0	4.8 – 12.8

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to 3 years. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Arm I (Sorafenib Tosylate)

Serious: 11/49 (22%)

Deaths: 1/49

Arm II (Placebo)

Serious: 6/36 (17%)

Deaths: 0/36

Crossover Group

Serious: 5/28 (18%)

Deaths: 0/28

Serious adverse events (30 terms)

Reaction	System	Arm I (Sorafenib Tosylate)	Arm II (Placebo)	Crossover Group
Diarrhea	Gastrointestinal disorders	—	—	—
Small intestinal obstruction	Gastrointestinal disorders	—	—	—
Fatigue	General disorders	—	—	—
Palmar-plantar erythrodysesthesia syndrome	Skin and subcutaneous tissue disorders	—	—	—
Anemia	Blood and lymphatic system disorders	—	—	—
Blood and lymphatic system disorders - Other, specify	Blood and lymphatic system disorders	—	—	—
Chest pain - cardiac	Cardiac disorders	—	—	—
Heart failure	Cardiac disorders	—	—	—
Palpitations	Cardiac disorders	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—
Gastric perforation	Gastrointestinal disorders	—	—	—
Malabsorption	Gastrointestinal disorders	—	—	—
Nausea	Gastrointestinal disorders	—	—	—
Pancreatitis	Gastrointestinal disorders	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—
Fever	General disorders	—	—	—
General disorders and administration site conditions - Other, specify	General disorders	—	—	—
Appendicitis	Infections and infestations	—	—	—
Sepsis	Infections and infestations	—	—	—
Injury, poisoning and procedural complications - Other, specify	Injury, poisoning and procedural complications	—	—	—
Alanine aminotransferase increased	Investigations	—	—	—
Hypertriglyceridemia	Metabolism and nutrition disorders	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—
Flank pain	Musculoskeletal and connective tissue disorders	—	—	—
Pregnancy, puerperium and perinatal conditions - Other, specify	Pregnancy, puerperium and perinatal conditions	—	—	—

Other adverse events (154 terms — click to expand)

Reaction	System	Arm I (Sorafenib Tosylate)	Arm II (Placebo)	Crossover Group
Fatigue	General disorders	—	—	—
Palmar-plantar erythrodysesthesia syndrome	Skin and subcutaneous tissue disorders	—	—	—
Hypertension	Vascular disorders	—	—	—
Papulopustular rash	Infections and infestations	—	—	—
Diarrhea	Gastrointestinal disorders	—	—	—
Nausea	Gastrointestinal disorders	—	—	—
Myalgia	Musculoskeletal and connective tissue disorders	—	—	—
Alopecia	Skin and subcutaneous tissue disorders	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—
Anorexia	Metabolism and nutrition disorders	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—
Constipation	Gastrointestinal disorders	—	—	—
Mucositis oral	Gastrointestinal disorders	—	—	—
Anemia	Blood and lymphatic system disorders	—	—	—
Alanine aminotransferase increased	Investigations	—	—	—
Platelet count decreased	Investigations	—	—	—
Headache	Nervous system disorders	—	—	—
Aspartate aminotransferase increased	Investigations	—	—	—
Hyperglycemia	Metabolism and nutrition disorders	—	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—	—
Rash maculo-papular	Skin and subcutaneous tissue disorders	—	—	—
Skin and subcutaneous tissue disorders - Other, specify	Skin and subcutaneous tissue disorders	—	—	—
White blood cell decreased	Investigations	—	—	—
Peripheral sensory neuropathy	Nervous system disorders	—	—	—
Rash acneiform	Skin and subcutaneous tissue disorders	—	—	—
Blood bilirubin increased	Investigations	—	—	—
Investigations - Other, specify	Investigations	—	—	—
Neutrophil count decreased	Investigations	—	—	—
Dry skin	Skin and subcutaneous tissue disorders	—	—	—
Chills	General disorders	—	—	—
Weight loss	Investigations	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—
Musculoskeletal and connective tissue disorder - Other, specify	Musculoskeletal and connective tissue disorders	—	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—	—
Nervous system disorders - Other, specify	Nervous system disorders	—	—	—
Eye disorders - Other, specify	Eye disorders	—	—	—
Gastrointestinal disorders - Other, specify	Gastrointestinal disorders	—	—	—
General disorders and administration site conditions - Other, specify	General disorders	—	—	—
Pain	General disorders	—	—	—

Most-reported serious reactions: Diarrhea, Small intestinal obstruction, Fatigue, Palmar-plantar erythrodysesthesia syndrome, Anemia, Blood and lymphatic system disorders - Other, specify, Chest pain - cardiac, Heart failure.

Data from ClinicalTrials.gov NCT02066181 adverse events section.

Sponsor's own description

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. \[Funding Source - FDA OOPD\]

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Sorafenib for Advanced and Refractory Desmoid Tumors.
   Gounder MM, Mahoney MR, Van Tine BA, Ravi V, et al · · 2018 · cited 325× · PMID 30575484 · DOI 10.1056/nejmoa1805052
2. An update on the management of sporadic desmoid-type fibromatosis: a European Consensus Initiative between Sarcoma PAtients EuroNet (SPAEN) and European Organization for Research and Treatment of Cancer (EORTC)/Soft Tissue and Bone Sarcoma Group (STBSG).
   Kasper B, Baumgarten C, Garcia J, Bonvalot S, et al · · 2017 · cited 256× · PMID 28961825 · DOI 10.1093/annonc/mdx323
3. Composite grading algorithm for the National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE).
   Basch E, Becker C, Rogak LJ, Schrag D, et al · · 2021 · cited 161× · PMID 33258687 · DOI 10.1177/1740774520975120
4. Evolving strategies for management of desmoid tumor.
   Riedel RF, Agulnik M. · · 2022 · cited 52× · PMID 35670122 · DOI 10.1002/cncr.34332
5. Activated Signaling Pathways and Targeted Therapies in Desmoid-Type Fibromatosis: A Literature Review.
   Timbergen MJM, Smits R, Grünhagen DJ, Verhoef C, et al · · 2019 · cited 33× · PMID 31165043 · DOI 10.3389/fonc.2019.00397
6. The landscape of tyrosine kinase inhibitors in sarcomas: looking beyond pazopanib.
   Wilding CP, Elms ML, Judson I, Tan AC, et al · · 2019 · cited 32× · PMID 31665941 · DOI 10.1080/14737140.2019.1686979
7. Molecular targeted therapy for advanced or metastatic soft tissue sarcoma.
   Yuan J, Li X, Yu S. · · 2021 · cited 15× · PMID 34844463 · DOI 10.1177/10732748211038424
8. Pediatric phase I trial of oral sorafenib and topotecan in refractory or recurrent pediatric solid malignancies.
   Reed DR, Mascarenhas L, Manning K, Hale GA, et al · · 2016 · cited 14× · PMID 26714427 · DOI 10.1002/cam4.598