Clinical Trials /

Pazopanib Hydrochloride in Treating Patients With Advanced Angiosarcoma

NCT01462630

Description:

This phase II trial studies how well pazopanib hydrochloride works in treating patients with advanced angiosarcoma. Pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Related Conditions:
  • Angiosarcoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pazopanib Hydrochloride in Treating Patients With Advanced Angiosarcoma
  • Official Title: Phase II Study Evaluating the Role of Pazopanib in Angiosarcoma

Clinical Trial IDs

  • ORG STUDY ID: OER-SAR-043
  • SECONDARY ID: NCI-2011-01314
  • SECONDARY ID: IRB#11-042
  • SECONDARY ID: OER-SAR-043
  • SECONDARY ID: P30CA006927
  • NCT ID: NCT01462630

Conditions

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

Interventions

DrugSynonymsArms
pazopanib hydrochlorideGW786034B, VotrientTreatment (enzyme inhibitor therapy)

Purpose

This phase II trial studies how well pazopanib hydrochloride works in treating patients with advanced angiosarcoma. Pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine the progression free survival (PFS) at 3 months and response rate defined as
      complete response (CR) and partial response (PR) in angiosarcoma patients treated with
      pazopanib.

      SECONDARY OBJECTIVES:

      I. To assess overall survival of patients treated with pazopanib. II. To gather more safety
      data for pazopanib in this patient population. III. To explore the ability of [F-18]
      fludeoxyglucose (FDG) (positron emission tomography [PET])/computed tomography (CT) imaging
      to assess response.

      OUTLINE:

      Patients receive pazopanib hydrochloride orally (PO) once daily (QD). Courses repeat every 21
      days in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up every 3 months for 2 years.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (enzyme inhibitor therapy)ExperimentalPatients receive pazopanib hydrochloride PO QD. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
  • pazopanib hydrochloride

Eligibility Criteria

        Inclusion Criteria:

          -  Subjects must provide written informed consent and Health Insurance Portability and
             Accountability Act (HIPAA) consent prior to performance of study-specific procedures
             or assessments and must be willing to comply with treatment and follow up

               -  Note: informed consent may be obtained prior to start of the specified screening
                  window

               -  Note: procedures conducted as part of the subject's routine clinical management
                  (e.g., blood count, imaging study such as bone scan) and obtained prior to
                  signing of informed consent may be utilized for screening or baseline purposes
                  provided these procedures are conducted as specified in the protocol

          -  Histologically or cytologically proven diagnosis of advanced stage angiosarcoma that
             is not amenable to treatment with curative intent; specify site of origin as cutaneous
             vs. non-cutaneous

          -  Eastern Cooperative Oncology Group (ECOG) performance status of =< 2

          -  Must have measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST)
             1.1 or cutaneous disease amenable to serial measurements should be present; a
             measurable lesion is defined as a lesion that can be accurately measured in at least
             one dimension with the longest diameter >= 10 mm with computed tomography (CT) scan;
             lesions that have been treated with therapeutic intent will be considered measurable
             if they have increased in size by more than 20%

          -  Absolute neutrophil count (ANC) >= 1.5 X 10^9/L

          -  Hemoglobin >= 9 g/dL (5.6 mmol/L)

          -  Platelets >= 100 X 10^9/L

          -  International normalized ratio (INR) =< 1.2 X upper limit of normal (ULN)

          -  Activated partial thromboplastin time (aPTT) =< 1.2 X ULN

          -  Total bilirubin =< 1.5 X ULN (may not have abnormalities in both bilirubin and
             transaminases)

          -  Alanine amino transferase (ALT) and aspartate aminotransferase (AST) =< 2.5 X ULN (may
             not have abnormalities in both bilirubin and transaminases)

          -  Serum creatinine =< 1.5 mg/dL (133 umol/L)

          -  Or, if serum creatinine > 1.5 mg/dL: calculated creatinine clearance (ClCR) > 50
             mL/min

          -  Urine Protein to Creatinine Ratio (UPC) < 1

          -  Able to swallow pills whole and retain oral medication

          -  A female is eligible to enter and participate in this study if the following apply:

          -  Non-childbearing potential (i.e., physiologically incapable of becoming pregnant),
             including any female who has had:

               -  A hysterectomy

               -  A bilateral oophorectomy (ovariectomy)

               -  A bilateral tubal ligation

               -  Is post-menopausal

          -  Subjects not using hormone replacement therapy (HRT) must have experienced total
             cessation of menses for >= 1 year and be greater than 45 years in age, OR, in
             questionable cases, have a follicle stimulating hormone (FSH) value > 40 mIU/mL and an
             estradiol value < 40pg/mL (< 140 pmol/L)

          -  Subjects using HRT must have experienced total cessation of menses for >= 1 year and
             be greater than 45 years of age OR have had documented evidence of menopause based on
             FSH and estradiol concentrations prior to initiation of HRT

          -  Childbearing potential, including any female who has had a negative serum pregnancy
             test within 2 weeks prior to the first dose of study treatment and for 3 months after
             the completion of treatment, preferably as close to the first dose as possible, and
             agrees to use adequate contraception; acceptable contraceptive methods, when used
             consistently and in accordance with both the product label and the instructions of the
             physician, are as follow:

               -  Complete abstinence from sexual intercourse for 14 days before exposure to
                  investigational product, through the dosing period, and for at least 21 days
                  after the last dose of investigational product

               -  Oral contraceptive, either combined or progestogen alone

               -  Injectable progestogen

               -  Implants of levonorgestrel

               -  Estrogenic vaginal ring

               -  Percutaneous contraceptive patches

               -  Intrauterine device (IUD) or intrauterine system (IUS) with a documented failure
                  rate of less than 1% per year

               -  Male partner sterilization (vasectomy with documentation of azoospermia) prior to
                  the female subject's entry into the study, and this male is the sole partner for
                  that subject

               -  Double barrier method: condom and an occlusive cap (diaphragm or cervical/vault
                  caps) with a vaginal spermicidal agent (foam/gel/film/cream/suppository)

          -  Female subjects who are lactating must discontinue nursing prior to the first dose of
             study drug and refrain from nursing throughout the treatment period and for 14 days
             following the last dose of study drug

          -  A male is eligible to enter and participate in this study if he and his female sexual
             partner in the reproductive age group agree to use effective methods of contraception

        Exclusion Criteria:

          -  Prior malignancy:

        Subjects with a history of a prior malignancy other than angiosarcoma who have been
        disease-free for at least 2 years prior to the first dose of study drug and/or subjects
        with a history of completely resected non-melanomatous skin carcinoma or successfully
        treated in situ carcinoma are eligible

          -  History or clinical evidence of central nervous system (CNS) metastases or
             leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS
             metastases, are asymptomatic, and have had no requirement for steroids or anti-seizure
             medications for 3 months prior to first dose of study drug; screening with CNS imaging
             studies (CT or magnetic resonance imaging [MRI]) is required only if clinically
             indicated or if the subject has a history of CNS metastases

          -  Clinically significant gastrointestinal (GI) abnormalities that may increase the risk
             for gastrointestinal bleeding including, but not limited to:

               -  Active peptic ulcer disease

               -  Known intraluminal metastatic lesion/s with risk of bleeding

               -  Inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease), or other
                  gastrointestinal conditions with increased risk of perforation

               -  History of abdominal fistula, gastrointestinal perforation, or intra abdominal
                  abscess within 28 days prior to beginning study treatment

               -  Clinically significant (> 1/2 teaspoon) hemoptysis or gastrointestinal hemorrhage
                  in the past 6 months

          -  Evidence of active bleeding or bleeding diathesis; recent hemoptysis (>= 1/2 teaspoon
             of red blood within 8 weeks before first dose of study drug)

          -  Clinically significant gastrointestinal abnormalities that may affect absorption of
             investigational product including, but not limited to:

               -  Malabsorption syndrome

               -  Major resection of the stomach or small bowel

          -  Corrected QT interval (QTc) > 480 msecs using Bazett's formula

          -  Left ventricular ejection fraction < 50%

          -  History of any one or more of the following cardiovascular conditions within the past
             6 months:

               -  Cardiac angioplasty or stenting

               -  Myocardial infarction

               -  Unstable angina

               -  Coronary artery bypass graft surgery

               -  Symptomatic peripheral vascular disease

               -  Class III or IV congestive heart failure, as defined by the New York Heart
                  Association (NYHA)

          -  Poorly controlled hypertension (defined as systolic blood pressure [SBP] of >= 140
             mmHg or diastolic blood pressure [DBP] of >= 90mmHg); Note: Initiation or adjustment
             of antihypertensive medication(s) is permitted prior to study entry; following
             antihypertensive medication initiation or adjustment, blood pressure (BP) must be
             re-assessed three times at approximately 2-minute intervals; at least 24 hours must
             have elapsed between anti-hypertensive medication initiation or adjustment and BP
             measurement; these three values should be averaged to obtain the mean diastolic blood
             pressure and the mean systolic blood pressure; the mean SBP / DBP ratio must be <
             140/90 mmHg in order for a subject to be eligible for the study

          -  Cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism
             or untreated deep venous thrombosis (DVT) within the past 6 months

               -  Note: subjects with recent DVT who have been therapeutically coagulated for at
                  least 6 weeks are eligible

          -  Major surgery or trauma within 28 days prior to first dose of investigational product
             and/or presence of any non-healing wound, fracture, or ulcer (procedures such as
             catheter placement not considered to be major surgery)

          -  Evidence of active bleeding or bleeding diathesis; recent hemoptysis (>= ½ teaspoon of
             red blood within 8 weeks before first dose of study drug)

          -  Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels (Note:
             tumor abutting the vessel is acceptable, but contiguous tumor and vessel is not; CT
             with contrast is strongly recommended to evaluate such lesions)

          -  Abnormal serum calcium, magnesium, or potassium levels

          -  Any serious and/or unstable pre-existing medical, psychiatric, or other condition that
             could interfere with subject's safety, provision of informed consent, or compliance to
             study procedures

          -  Use of any prohibited medication within the timeframes

          -  Treatment with any of the following therapies:

               -  Radiation therapy, surgery or tumor embolization within 14 days prior to the
                  first dose of pazopanib hydrochloride OR

               -  Chemotherapy, immunotherapy, biologic therapy, investigational therapy or
                  hormonal therapy within 14 days or five half-lives of a drug (whichever is
                  longer) prior to the first dose of pazopanib

               -  Patients who require chronic use of strong cytochrome P450 3A4 (CYP3A4)
                  inhibitors or inducers including but not limited to grapefruit juice

          -  Any ongoing toxicity from prior anti-cancer therapy that is > Grade 1 (except
             hemoglobin value) and/or that is progressing in severity, except alopecia

          -  Previous exposure to pazopanib hydrochloride or a vascular endothelial growth factor
             receptor (VEGFR) targeted kinase therapy, except for bevacizumab or VEGFR-Trap
             (Aflibercept)

          -  Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs
             chemically related to pazopanib
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:PFS
Time Frame:3 months
Safety Issue:
Description:Estimated using the method of Kaplan and Meier.

Secondary Outcome Measures

Measure:Response rate defined as CR and PR in angiosarcoma patients treated with pazopanib hydrochloride
Time Frame:3 months
Safety Issue:
Description:Standard estimates of the binomial proportion will be used to estimate and place confidence bounds on the several response rates.
Measure:Overall survival of patients treated with pazopanib hydrochloride
Time Frame:Up to 2 years
Safety Issue:
Description:Estimated using the method of Kaplan and Meier.
Measure:Evaluation of toxicity and safety for pazopanib hydrochloride in this patient population
Time Frame:Up to 2 years
Safety Issue:
Description:
Measure:[F-18] FDG PET/CT as an imaging agent in predicting efficacy or early response as compared with CT imaging
Time Frame:Up to 2 years
Safety Issue:
Description:Descriptive statistics will include mean, SD, median, minimum, and maximum for continuous variables and the numbers and percentages for categorical variables. Summary statistics for changes in SUVs, tumor to background ratios, lesion size, and comparison scores will be analyzed and presented.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Fox Chase Cancer Center

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