Clinical Trials /

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

NCT02048722

Description:

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.

Related Conditions:
  • Angiosarcoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: NU 13S02
  • SECONDARY ID: NCI-2013-02278
  • SECONDARY ID: STU00087654
  • SECONDARY ID: ONC-2013-129
  • SECONDARY ID: NU 13S02
  • SECONDARY ID: P30CA060553
  • NCT ID: NCT02048722

Conditions

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

Interventions

DrugSynonymsArms
regorafenibBAY 73-4506, multikinase inhibitor BAY 73-4506, StivargaTreatment (regorafenib)

Purpose

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.

Detailed Description

      PRIMARY OBJECTIVES:

      I. 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:

      I. 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).

      V. 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.
    

Trial Arms

NameTypeDescriptionInterventions
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.
  • regorafenib

Eligibility Criteria

        Inclusion Criteria:

          -  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

          -  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

        Exclusion Criteria:

          -  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

          -  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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-Free Survival (PFS) at 4 months
Time Frame:At 4 months (of treatment)
Safety Issue:
Description:PFS will be evaluated at 4 months and will be defined as the absence of disease progression.

Secondary Outcome Measures

Measure:Progression-Free Rate (PFR) at 3 and 6 months
Time Frame:Assessed at 3 months and 6 months
Safety Issue:
Description:Patients will be evaluated at 3 and 6 months for the absence of disease progression, this data will be used to calculate the PFR.
Measure:Progression-free survival (PFS)
Time Frame:The duration of time from start of treatment until time of progression, up to 5 years
Safety Issue:
Description:PFS will be measured as the duration of time from the start of treatment until the time of disease progression, patients will be followed-up with for up to 5 years.
Measure:Overall survival
Time Frame:From start of treatment up to 5 years
Safety Issue:
Description:Once off-treatment, patients will be followed for overall survival for up to 5 years.
Measure:Response rate (of tumor to treatment)
Time Frame:At baseline and after every 2 cycles, up to 7 years
Safety Issue:
Description: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.
Measure:Rate and duration of tumor control
Time Frame:At baseline and after every 2 cycles, up to 7 years
Safety Issue:
Description: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.
Measure:Number of Grade 1, 2, 3, 4, and 5 Adverse Events Observed During Study Treatment (Defined by CTCAE v 4.0)
Time Frame:Measured at baseline & at each cycle, for up to 7 years
Safety Issue:
Description:

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Northwestern University

Last Updated

September 10, 2018