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Adult AngiosarcomaPhase 2NCT02048722

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

A Phase 2 study testing regorafenib in people with Adult Angiosarcoma and Recurrent Adult Soft Tissue Sarcoma, run by Northwestern University at 7 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
regorafenib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
31 participants
Where
7 sitesUnited States
Study dates
13 Jun 2014to 12 Oct 2021
Phase
Phase 2

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

  • 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
Show all 22Show fewer
  • 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
  • Absolute neutrophil count > 1500/mm^3
  • If baseline urine protein creatinine (UPC) >= 1, a 24-hour urine protein must be assessed; patients must have a 24-hour urine protein value < grade 3 (> 3.5 g/24 hours) to be eligible
  • NOTE: Blood transfusion to meet the above criteria will not be allowed; NOTE: Patients who are prophylactically treated with an agent such as warfarin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in coagulation parameters exists; close monitoring of at least weekly evaluations will be performed until INR/PTT is stable based on a measurement that is pre-dose as defined by the local standard of care
  • Women of childbearing potential must have a negative serum pregnancy test performed within 7 days prior to the start of study drug; post-menopausal women (defined as age >= 50 years and no menses for at least 1 year) and surgically sterilized women are not required to undergo a pregnancy test
  • Subjects (men and women) of childbearing potential must agree to use adequate contraception beginning at registration until at least 3 months after the last dose of study drug; the definition of adequate contraception will be based on the judgment of the principal investigator
  • Subject must be able to swallow and retain oral medication
  • Subjects must be able to understand and be willing to sign the written informed consent form; a signed informed consent form must be appropriately obtained prior to the conduct of any trial-specific procedure

Who cannot join

  • 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
Show all 38Show fewer
  • 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
  • Presence of a non-healing wound, non-healing ulcer, or bone fracture
  • Renal failure requiring hemo-or peritoneal dialysis
  • Dehydration > grade 1
  • Interstitial lung disease with ongoing signs and symptoms at the time of registration
  • Pleural effusion or ascites that causes respiratory compromise (>= grade 2 dyspnea)
  • History of organ allograft (including corneal transplant)
  • Known or suspected allergy or hypersensitivity to any of the study drugs, study drug classes, or excipients of the formulations given during the course of this trial
  • Any malabsorption condition
  • Evidence of abdominal fistula, gastrointestinal (GI) perforation or intraabdominal abscess
  • Women who are pregnant or breast-feeding
  • Concurrent anti-cancer therapy (chemotherapy, surgery, immunotherapy, biologic therapy, or tumor embolization) other than study treatment (regorafenib)
  • Prior use of regorafenib
  • Prior use of sorafenib
  • Use of cytotoxic chemotherapy within 21 days of registration
  • Use of targeted therapy within two half-lives of registration
  • Radiation directed at target lesion within 28 days of registration
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before registration
  • Therapeutic anticoagulation with Vitamin-K antagonists (e.g., warfarin) or with heparins and heparinoids; NOTE: Prophylactic anticoagulation as described below is allowed:
  • Low dose warfarin (1 mg orally, once daily) with prothrombin time (PT)-international normalized ratio (INR) =< 1.5 x ULN is permitted; infrequent bleeding or elevations in PT-INR have been reported in some subjects taking warfarin while on regorafenib therapy; therefore, subjects taking concomitant warfarin should be monitored regularly for changes in PT, PT-INR or clinical bleeding episodes
  • Low dose aspirin (=< 100 mg daily)
  • Prophylactic doses of heparin
  • Any condition which, in the investigator's opinion, makes the subject unsuitable for trial participation
  • Substance abuse, medical, psychological or social conditions that may interfere with the subject's participation in the study or evaluation of the study results

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

United States7 sites

  • Northwestern University

    Chicago, Illinois, 60611

  • University of Iowa

    Iowa City, Iowa, 52246

  • Mayo Clinic in Florida

    Jacksonville, Florida, 32224-9980

  • University of Minnesota Medical Center-Fairview

    Minneapolis, Minnesota, 55455

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • Sarcoma Oncology Center

    Santa Monica, California, 90403

  • Washington University-St. Louis

    St Louis, Missouri, 63110

Other trials in United States

About this study

Official title: Multicenter, Open-Label Phase II Study of Daily Oral Regorafenib for Chemotherapy-Refractory, Metastatic and Locally Advanced Angiosarcoma

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To define the progression-free survival (PFS) at 4 months with daily oral regorafenib (160 mg) in previously treated locally advanced/metastatic angiosarcoma patients

SECONDARY OBJECTIVES:

  1. Progression-free rate at 3 and 6 months. II. Progression-free survival. III. Overall survival (up to 5 years). IV. Response rate (by Response Evaluation Criteria in Solid Tumors [RECIST] version [v] 1.1).
  2. Rate and duration of tumor control (complete response [CR] + partial response [PR] + stable disease [SD]).

VI. Safety/tolerability of regorafenib.

OUTLINE:

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

After completion of study treatment, patients are followed up every 6 months for up to 5 years.

Being tested
regorafenib
Medical subject headings
Hemangiosarcoma, Sarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • regorafenibDrug

    Also called BAY 73-4506, multikinase inhibitor BAY 73-4506, Stivarga

    Given PO

Study groups in NCT02048722
Study groupRoleWhat they receive
Treatment (regorafenib)ExperimentalPatients receive regorafenib PO QD on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: regorafenib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: At 4 months (of treatment)

Secondary outcomes (6)

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

    The progression-free survival (PFS) at 3 and 6 months will be defined as the number of patients with progression absent at 3 months and 6 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.

    Measured: Assessed at 3 months and 6 months

  2. Median Progression-free Survival (PFS)

    The median progression-free rate (PFR) will be defined as the number of patients with progression absent 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 for up to 5 years and will be estimated using Kaplan-Meier methods.

    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.

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

  3. Overall Survival

    Overall survival will be defined as the time from start of treatment until death from any cause and will be estimated using Kaplan-Meier methods and reported as a survival probability. Patients that are alive at the time of data analysis will be censored at the date of known survival status.

    Measured: From start of treatment up to 5 years

  4. Response Rate

    Imaging (such as a CT scan) will be done at baseline (within 4 weeks before the first dose) then after every 2 cycles while on treatment for tumor response evaluation. Response 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. Best response of each patient will be used and responses will be defined as the following:

    Complete response (CR): Disappearance of all target lesions Partial response (PR): > 30% decrease in the baseline sum diameters of target lesions

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

  5. Rate of Tumor Control

    Imaging will be used at baseline then after every 2 cycles while on treatment to measure tumor size and response to treatment, the data collected from all patients on study will be used to calculate the rate and duration of tumor control.

    Response 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. Response and stable disease will be defined as the following:

    Complete response (CR): Disappearance of all target lesions Partial response (PR): > 30% decrease in the baseline sum diameters of target lesions Stable disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study

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

  6. Number of Grade 1, 2, 3, 4, and 5 Related Adverse Events Observed During Study Treatment (Defined by CTCAE v 4.0)

    Overall worst grade related toxicity (number of patients) was collected from the start of treatment until 30 days post the last treatment where patients were treated until progressive disease or unacceptable toxicity or patient withdrawal of treatment. All Adverse events that were determined to be at least possibly related to treatment are reported.

    All adverse events will be graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

    The severity of an AE is graded as follows:

    Mild (grade 1): the event causes discomfort without disruption of normal daily activities.

    Moderate (grade 2): the event causes discomfort that affects normal daily activities.

    Severe (grade 3): the event makes the patient unable to perform normal daily activities or significantly affects his/her clinical status.

    Life-threatening (grade 4): the patient was at risk of death at the time of the event.

    Fatal (grade 5): the event caused death

    Measured: From treatment initiation though 30 days post the last treatment for a max of 12 cycles where one cycle is 28 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Jan 2014 (estimated)
  2. Study start13 Jun 2014
  3. Primary completion14 Oct 2019
  4. Study completion12 Oct 2021

Resources

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
31 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02048722
Sponsor's protocol ID
NU 13S02
Other IDs
NCI-2013-02278, STU00087654, ONC-2013-129, NU 13S02, P30CA060553
Status last verified
Mar 2022
First submitted
22 Jan 2014
Last updated
25 Apr 2022
Data monitoring committee
Yes

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