Pazopanib Hydrochloride in Treating Patients With Recurrent or Persistent Uterine Cancer



Status:Active, not recruiting
Conditions:Cancer
Therapuetic Areas:Oncology
Healthy:No
Age Range:18 - Any
Updated:4/21/2016
Start Date:January 2011

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A Phase II Evaluation of Pazopanib (NSC # 737754) in the Treatment of Recurrent or Persistent Carcinosarcoma of the Uterus

This phase II trial studies how well pazopanib hydrochloride works in treating patients with
uterine cancer that has come back or has not responded to treatment. Pazopanib hydrochloride
may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Pazopanib hydrochloride may also stop the growth of uterine cancer by blocking blood flow to
the tumor.

PRIMARY OBJECTIVES:

I. To assess the activity of pazopanib in patients with persistent or recurrent
carcinosarcoma of the uterus as measured by the proportion of patients who survive
progression-free for at least 6 months and the proportion of patients who have objective
tumor response (complete or partial).

SECONDARY OBJECTIVES:

I. To determine the frequency and severity of adverse events as assessed by Common
Terminology Criteria of Adverse Events version 4.0 (CTCAE v4.0).

II. To determine the duration of progression-free survival and overall survival.

OUTLINE: This is a multicenter study.

Patients receive pazopanib hydrochloride orally (PO) once daily (QD) on days 1-28. Courses
repeat every 28 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 and
then every 6 months for 3 years.

Inclusion Criteria:

- Patients must have histologically confirmed uterine carcinosarcoma which is
persistent or recurrent; acceptable histological type is defined as carcinosarcoma
(malignant mixed müllerian tumor), homologous or heterologous type

- Patients must have measurable disease

- Measurable disease is defined by Response Evaluation Criteria in Solid Tumors
(RECIST) (version 1.1)

- Measurable disease is defined as at least one lesion that can be accurately
measured in at least one dimension (longest diameter to be recorded)

- Each lesion must be greater than or equal to 10 mm when measured by computed
tomography (CT), magnetic resonance imaging (MRI), or caliper measurement by
clinical exam or greater than or equal to 20 mm when measured by chest x-ray

- Lymph nodes must be greater than or equal to 15 mm in short axis when measured
by CT or MRI

- Patients must have at least one "target lesion" to be used to assess response on this
protocol as defined by RECIST version 1.1

- Tumors within a previously irradiated field will be designated as "non-target"
lesions unless progression is documented or a biopsy is obtained to confirm
persistence at least 90 days following completion of radiation therapy

- Patients must not be eligible for a higher priority Gynecologic Oncology Group (GOG)
protocol, if one exists

- In general, this would refer to any active GOG phase III protocol or rare tumor
protocol for the same patient population

- Patients must have a GOG performance status of 0, 1, or 2

- Recovery from effects of recent surgery, radiotherapy, or chemotherapy

- Patients should be free of active infection requiring antibiotics (with the
exception of uncomplicated urinary tract infection [UTI])

- Any hormonal therapy directed at the malignant tumor must be discontinued at
least one week prior to registration

- Any other prior therapy (chemotherapy) directed at the malignant tumor, must be
discontinued at least three weeks prior to registration

- At least 4 weeks must have elapsed since the patient underwent any major surgery
(e.g., major: hysterectomy, resection of a lung nodule - minor: central venous
access catheter placement)

- Patients must have had one prior chemotherapeutic regimen for management of
carcinosarcoma; initial treatment may include chemotherapy, chemotherapy and
radiation therapy, and/or consolidation/maintenance therapy; chemotherapy
administered in conjunction with primary radiation as a radio-sensitizer WILL be
counted as a systemic chemotherapy regimen

- Patients are allowed to receive, but are not required to receive, one additional
cytotoxic regimen for management of recurrent or persistent disease according to the
following definition:

- Cytotoxic regimens include any agent that targets the genetic and/or mitotic
apparatus of dividing cells, resulting in dose-limiting toxicity to the bone
marrow and/or gastrointestinal mucosa

- Note: patients on this non-cytotoxic study are allowed to receive one additional
cytotoxic chemotherapy regimen for management of recurrent or persistent
disease, as defined above; however, due to the novel nature of biologic
compounds, patients are encouraged to enroll on second-line non-cytotoxic
studies prior to receiving additional cytotoxic therapy

- Patients must have NOT received any non-cytotoxic chemotherapy for management of
recurrent or persistent disease; prior hormonal therapy is permitted

- Absolute neutrophil count (ANC) greater than or equal to 1,500/mcL

- Platelets greater than or equal to 100,000/mcL

- Hemoglobin level greater than or equal to 9 g/dL

- Creatinine less than or equal to 1.5 x institutional upper limit of normal (ULN)

- Urine protein/creatinine ratio (UPCR) must be less than 1 (or urinary protein less
than 1.0 g/24 hours)

- Bilirubin less than or equal to 1.5 x ULN (subjects with Gilbert syndrome and
elevations of indirect bilirubin only are eligible)

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or
equal to 2.5 x ULN

- Alkaline phosphatase less than or equal to 2.5 x ULN

- Subjects who have BOTH bilirubin greater than ULN and AST/ALT greater than ULN are
not eligible

- Specifically, if bilirubin is greater than 1 x ULN but less than or equal to 1.5
x ULN, THEN the AST and ALT must be less than or equal to ULN for patient to be
eligible; if AST and/or ALT are greater than 1 x ULN but less than or equal to
2.5 x ULN, THEN the bilirubin must be less than or equal to ULN for patient to
be eligible

- Prothrombin time (PT) such that international normalized ratio (INR) is less than or
equal to 1.5 x ULN (or an in-range INR, usually between 2 and 3, if a patient is on a
stable dose of therapeutic warfarin) and a partial thromboplastin time (PTT) less
than or equal to 1.5 x ULN

- Patients with a history of hypothyroidism/hyperthyroidism must have had stable
well-controlled thyroid function for a minimum of 2 months as a condition for
eligibility and that all other patients must have normal baseline thyroid function
tests (thyroid stimulating hormone [TSH], triiodothyronine [T]3, T4)

- Patients must have the ability to understand and sign an approved informed consent
and authorization permitting release of personal health information

- Patients who have met the pre-entry requirements

- Patients must be capable of taking and absorbing oral medications; a patient must be
clear of the following:

- Any lesion, whether induced by tumor, radiation or other conditions, which makes
it difficult to swallow tablets

- Prior surgical procedures affecting absorption including, but not limited to
major resection of stomach or small bowel

- Active peptic ulcer disease

- Malabsorption syndrome

- Patients must be capable of taking and absorbing oral medications

- A patient must be clear of the following:

- Any lesion, whether induced by tumor, radiation, or other conditions, which
makes it difficult to swallow tablets

- Prior surgical procedures affecting absorption including, but not limited to,
major resection of stomach or small bowel

- Active peptic ulcer disease

- Malabsorption syndrome

- Any concomitant medications that are associated with a risk of corrected QC (QTc)
prolongation and/or Torsades de pointes should be discontinued or replaced with drugs
that do not carry these risks, if possible; patients who must take medication with a
risk of possible risk of Torsades de pointes should be watched carefully for symptoms
of QTc prolongation, such as syncope

- Patients with personal or family history of congenital long QTc syndrome are NOT
eligible

- Strong inhibitors of cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4)
are prohibited; grapefruit juice is also an inhibitor of CYP450 and should not be
taken with pazopanib; CYP3A4 Inducers: strong inducers of CYP3A4 are prohibited;
cytochrome P450 (CYP) substrates: concomitant use of agents with narrow therapeutic
windows that are metabolized by CYP3A4, cytochrome P450, family 2, subfamily D,
polypeptide 6 (CYP2D6), or cytochrome P450, family 2, subfamily C, poly peptide 8
(CYP2C8) is not recommended

- Patients of childbearing potential must have a negative pregnancy test prior to the
study treatment and agree to be practicing an effective form of contraception
throughout study treatment; pregnant women are excluded from this study

Exclusion Criteria:

- Patients who have had prior therapy with pazopanib

- Patients with other invasive malignancies, with the exception of non-melanoma skin
cancer, are excluded if there is any evidence of other malignancy being present
within the last three years; patients are also excluded if their previous cancer
treatment contraindicates this protocol therapy

- Patients who have received prior radiotherapy to any portion of the abdominal cavity
or pelvis OTHER THAN for the treatment of uterine carcinosarcoma within the last
three years are excluded; prior radiation for localized cancer of the breast, head
and neck, or skin is permitted, provided that it was completed more than three years
prior to registration, and the patient remains free of recurrent or metastatic
disease

- Patients who have received prior chemotherapy for any abdominal or pelvic tumor OTHER
THAN for the treatment of uterine carcinosarcoma within the last three years are
excluded; patients may have received prior adjuvant chemotherapy for localized breast
cancer, provided that it was completed more than three years prior to registration,
and that the patient remains free of recurrent or metastatic disease

- Patients with clinically significant cardiovascular disease; this includes:

- Patients must have blood pressure (BP) no greater than 140 mmHg (systolic) and
90 mmHg (diastolic) for eligibility

- Myocardial infarction or unstable angina within 6 months of the first date of
pazopanib therapy

- New York Heart Association (NYHA) class II or greater congestive heart failure

- History of serious ventricular arrhythmia (i.e., ventricular tachycardia or
ventricular fibrillation) or cardiac arrhythmias requiring anti-arrhythmic
medications; this does not include asymptomatic, atrial fibrillation with
controlled ventricular rate

- Women who have received prior anthracycline (e.g., doxorubicin and/or liposomal
doxorubicin) and who have an ejection fraction less than the institutional lower
limit of normal will be excluded from the study; patients with a prior life time
exposure to doxorubicin (or liposomal doxorubicin) of greater than 300 mg/m^2
are NOT eligible

- CTCAE grade 2 or greater peripheral vascular disease

- History of cerebrovascular accident (CVA, stroke), transient ischemic attack
(TIA) or subarachnoid hemorrhage within six months of the first date of
pazopanib therapy

- Women with a baseline QTc >= 480 milliseconds

- History of cardiac angioplasty or stenting within 6 months prior to
registration; history of coronary artery bypass graft surgery within 6 months
prior to registration

- A patient with arterial thrombosis within 6 months prior to enrollment

- Patients with history or evidence upon physical examination of central nervous system
(CNS) disease, including primary brain tumor, seizures not controlled with standard
medical therapy or any brain metastases

- Patients with active bleeding or pathologic conditions that carry high risk of
bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major
vessels

- Patients with serious, non-healing wound, ulcer, or bone fracture; this includes
history of abdominal fistula, gastrointestinal perforation or intra-abdominal abscess
within 28 days prior to the first date of pazopanib therapy; patients with underlying
lesions that caused the fistula or perforation in the past that have not been
corrected

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to pazopanib

- Human immunodeficiency virus (HIV)-positive subjects on combination antiretroviral
therapy are ineligible

- Patients who are nursing; patients who are lactating should discontinue nursing prior
to the first dose of study drug and should refrain from nursing throughout the
treatment period and for 14 days following the last dose of study drug

- Patients with any condition that may increase the risk of gastrointestinal bleeding
or gastrointestinal perforation, including:

- Active peptic ulcer disease

- Known gastrointestinal intraluminal metastatic lesions (gastrointestinal serosa
metastatic lesion are permitted)

- Inflammatory bowel disease (e.g., ulcerative colitis, Crohn's disease)

- History of hemoptysis in excess of 2.5 mL (1/2 teaspoon) within 8 weeks prior to
first dose of pazopanib

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection or psychiatric illness/social situations that would limit compliance with
study requirements
We found this trial at
41
sites
100 Grand St
New Britain, Connecticut 06050
(860) 224-5011
The Hospital of Central Connecticut The Hospital of Central Connecticut is dedicated to fostering, sustaining...
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1 Hurley Plaza
Flint, Michigan 48503
(810) 262-9000
Hurley Medical Center From its founding in 1908, Hurley Medical Center has devoted itself to...
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1200 Old York Road
Abington, Pennsylvania 19001
(215) 481–2000
Abington Memorial Hospital Abington Memorial Hospital (AMH) is a 665-bed, regional referral center and teaching...
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5301 McAuley Drive
Ann Arbor, Michigan 48197
734-712-3456
Saint Joseph Mercy Hospital St. Joseph Mercy Ann Arbor Hospital is a 537-bed teaching hospital...
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Ann Arbor, Michigan 48106
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13001 E. 17th Pl.
Aurora, Colorado 80045
303-724-5000
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Chapel Hill, North Carolina 27599
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Charlotte, North Carolina 28204
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Charlotte, North Carolina 28204
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5841 S Maryland Ave
Chicago, Illinois 60637
1-773-702-6180
University of Chicago Comprehensive Cancer Center The University of Chicago Comprehensive Cancer Center (UCCCC) is...
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10900 Euclid Ave
Cleveland, Ohio 44106
216-368-2000
Case Western Reserve Univ Continually ranked among America's best colleges, Case Western Reserve University has...
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2500 Metrohealth Dr
Cleveland, Ohio 44109
(216) 778-7800
MetroHealth Med Ctr The MetroHealth System is one of the largest, most comprehensive health care...
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3535 Olentangy River Rd
Columbus, Ohio 43214
(614) 566-5000
Riverside Methodist Hospital Serving central Ohio since 1892, Riverside Methodist Hospital is consistently ranked one...
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Dearborn, Michigan 48123
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22101 Moross Rd
Detroit, Michigan 48236
(313) 343-4000
Saint John Hospital and Medical Center Founded in 1952, St. John Hospital and Medical Center...
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2301 Erwin Rd
Durham, North Carolina 27710
919-684-8111
Duke Univ Med Ctr As a world-class academic and health care system, Duke Medicine strives...
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420 S Saginaw St
Flint, Michigan 48502
810-232-3522
Genesys Regional Medical Center-West Flint Campus The health care team at Genesys Downtown Flint Health...
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1 Genesys Pkwy
Grand Blanc, Michigan 48439
(810) 606-5000
Genesys Regional Medical Center Genesys Health System, a member of Ascension Health, is a group...
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Indianapolis, Indiana 46260
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535 Barnhill Dr
Indianapolis, Indiana 46202
(888) 600-4822
Indiana University Melvin and Bren Simon Cancer Center At the IU Simon Cancer Center, more...
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205 NE Ave
Jackson, Michigan 49201
(517) 788-4800
Allegiance Health Allegiance Health is a community-owned and locally-governed health system in Jackson, Michigan. We...
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1215 E Michigan Ave
Lansing, Michigan 48912
(517) 364-1000
Sparrow Hospital Sparrow has grown to become the region's largest health system, and its diverse...
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Livonia, Michigan 48154
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9485 Mentor Ave
Mentor, Ohio 44060
(440) 205-5755
Lake University Ireland Cancer Center Lake Health is a private, not-for-profit leader in community health...
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1275 York Ave
New York, New York 10021
(212) 639-2000
Memorial Sloan Kettering Cancer Center Memorial Sloan Kettering Cancer Center — the world's oldest and...
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940 NE 13th St
Oklahoma City, Oklahoma 73190
(405) 271-6458
University of Oklahoma Health Sciences Center The OU Health Sciences Center is composed of seven...
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8303 Dodge Street
Omaha, Nebraska 68114
(402) 354–4000
Nebraska Methodist Hospital Methodist Hospital is a general medical and surgical hospital in Omaha, NE....
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Orlando, Florida 32803
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Pontiac, Michigan 48341
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2601 Electric Ave
Port Huron, Michigan 48060
(810) 985-1500
Saint Joseph Mercy Port Huron St. Joseph Mercy Hospital, Port Huron, MI is a 164-bed...
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Providence, Rhode Island 02905
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800 S Washington Ave
Saginaw, Michigan 48601
(989) 907-8000
Saint Mary's of Michigan At St. Mary's of Michigan, we continue to grow our outreach...
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Springfield, Missouri 65804
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3801 South National Avenue
Springfield, Missouri 65807
(417) 269-6000
CoxHealth South Hospital U.S. News & World Report has ranked CoxHealth one of Missouri's best...
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11800 E 12 Mile Rd
Warren, Michigan 48093
(586) 573-5000
Saint John Macomb-Oakland Hospital St. John Macomb-Oakland Hospital, Macomb Center, is a 376-bed facility offering...
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Washington, District of Columbia
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