Daily Oral Regorafenib for Chemotherapy-Refractory, Metastatic and Locally Advanced Angiosarcoma

NCT02048722 | Completed Phase 2 Results DMC

• 5 other identifiers: NU 13S02NCI-2013-02278STU00087654ONC-2013-129P30CA060553
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 7

Brief Summary

The purpose of this study is to see whether a drug called regorafenib might be effective in treating angiosarcoma. This study is for patients who have angiosarcoma that has gotten worse after they received chemotherapy. Regorafenib is a type of drug called a kinase inhibitor. Regorafenib interferes with how some kinase proteins work. Some of these kinases in cancer cells might normally help the cancer cells grow or form new blood vessels that could feed a growing tumor. By blocking these proteins, regorafenib may help stop the growth of certain cancers.

Conditions

Adult Angiosarcoma; Recurrent Adult Soft Tissue Sarcoma; Stage III Adult Soft Tissue Sarcoma; Stage IV Adult Soft Tissue Sarcoma

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS) at 4 Months

  The progression-free survival (PFS) at 4 months will be defined as the number of patients with progression absent at 4 months divided by the total number of evaluable study patients. This will be measured from start of treatment until time of progression or death, whichever occurs first and will be estimated using Kaplan-Meier methods and reported as a survival probability. Progression will be evaluated using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 Committee. Changes in only the largest diameter (unidimensional measurement) of the tumor lesions are used in RECIST v 1.1. Progression will be defined as: Progressive disease (PD): \> 20% increase in the sum diameters of target lesions, taking as reference the smallest sum diameters while on study. The sum diameters must also demonstrate an absolute increase of 5 mm. The appearance of one or more new lesions also qualifies as PD.

  At 4 months (of treatment)

Secondary Outcomes (6)

• Progression-Free Survival (PFS) at 3 and 6 Months

  Assessed at 3 months and 6 months

• Median Progression-free Survival (PFS)

  The duration of time from start of treatment until time of progression, up to 5 years

• Overall Survival

  From start of treatment up to 5 years

• Response Rate

  At baseline and after every 2 cycles, up to 12 cycles where one cycle is 28 days

• Rate of Tumor Control

  At baseline and after every 2 cycles, up to 12 cycles where one cycle is 28 days

Study Arms (1)

Treatment (regorafenib)

EXPERIMENTAL

Patients receive regorafenib PO QD on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: regorafenib

Interventions

regorafenib DRUG

Given PO

Also known as: BAY 73-4506, multikinase inhibitor BAY 73-4506, Stivarga

Treatment (regorafenib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Life expectancy of at least 4 months
• Histologically confirmed angiosarcoma
• Tumor deemed unresectable or metastatic
• Measurable disease per RECIST v 1.1
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
• Progressive disease under last palliative therapy with a history of prior ifosfamide, doxorubicin or taxane therapy for angiosarcoma; up to 4 prior therapies are allowed
• All acute toxic effects of any prior treatment have resolved to grade 1 or less (by National Cancer Institute-Common Terminology Criteria for Adverse Events \[NCI-CTCAE\] v 4.0) at the time of registration; NOTE: Exceptions to this criterion will include alopecia and fatigue
• Total bilirubin =\< 1.5 x the upper limits of normal (ULN)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 2.5 x ULN (=\< 5 x ULN for subjects with liver involvement of their cancer)
• Alkaline phosphatase limit =\< 2.5 x ULN (=\< 5 x ULN for subjects with liver involvement of their cancer)
• Lipase =\< 1.5 x the ULN
• Serum creatinine =\< 1.5 x the ULN
• International normalized ratio (INR)/partial thromboplastin time (PTT) \< 1.5 x ULN
• Platelet count \> 100000/mm\^3
• Hemoglobin \> 9 g/dL

You may not qualify if:

• Uncontrolled hypertension (systolic pressure \> 140 mmHg or diastolic pressure \> 90 mmHg on repeated measurement) despite optimal medical management
• Active or clinically significant cardiac disease including:
• Congestive heart failure - New York Heart Association \> class II
• Active coronary artery disease
• Cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin
• Unstable angina (anginal symptoms at rest), new-onset angina within 3 months before registration, or myocardial infarction within 6 months before registration
• Evidence or history of bleeding diathesis or coagulopathy
• Any hemorrhage or bleeding event grade 3 within 4 weeks prior to registration
• Subjects with thrombotic, embolic, venous, or arterial events, such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 6 months of informed consent
• Subjects with any previously untreated or concurrent cancer unrelated to angiosarcoma; NOTE: Exceptions include cervical cancer in-situ, treated basal cell carcinoma, or superficial bladder tumor; subjects surviving a cancer that was curatively treated and without evidence of disease for more than 3 years before registration are allowed; all treatments must have been completed at least 3 years prior to registration
• Patients with pheochromocytoma
• Patients with severe hepatic impairment (Child-Pugh class C)
• Known history of human immunodeficiency virus (HIV) infection or current chronic or active hepatitis B or C infection requiring treatment with antiviral therapy
• Ongoing infection \> grade 2
• Evidence of significant central nervous system disease including seizure disorder requiring medication, symptomatic metastatic brain or meningeal tumors

Sponsors & Collaborators

• Northwestern University: lead
• Bayer: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (7)

Sarcoma Oncology Center

Santa Monica, California, 90403, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Iowa

Iowa City, Iowa, 52246, United States

Location

University of Minnesota Medical Center-Fairview

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Washington University-St. Louis

St Louis, Missouri, 63110, United States

Location

MeSH Terms

Conditions

Hemangiosarcoma; Sarcoma

Interventions

regorafenib

Condition Hierarchy (Ancestors)

Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Vascular Tissue

Results Point of Contact

• Title: Mary Mulcahy, MD
• Organization: Northwestern University

m-mulcahy@northwestern.edu

312 695 4440

Study Officials

• Mark Agulnik, M.D.

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 22, 2014
• First Posted: January 29, 2014
• Study Start: June 13, 2014
• Primary Completion: October 14, 2019
• Study Completion: October 12, 2021
• Last Updated: April 25, 2022
• Results First Posted: July 29, 2020

Record last verified: 2022-03

Locations

US (7)