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A Phase II Evaluation of Pazopanib (NSC # 737754, IND #75648) in the Treatment of Recurrent or Persistent Carcinosarcoma of the Uterus

Phase 2
18 Years
Open (Enrolling)
Recurrent Uterine Sarcoma, Uterine Carcinosarcoma

Thank you

Trial Information

A Phase II Evaluation of Pazopanib (NSC # 737754, IND #75648) in the Treatment of Recurrent or Persistent Carcinosarcoma of the Uterus


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).


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 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 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 CT, 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 have had one prior chemotherapeutic regimen for management of

- 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 must not be eligible for a higher priority 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

- No patients with history or evidence upon physical examination of CNS disease,
including primary brain tumor, seizures not controlled with standard medical therapy,
or any brain metastases

- GOG performance status of 0, 1, or 2

- 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)

- AST and ALT less than or equal to 2.5 x ULN AND 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

- PT such that international normalized ratio (INR) is ≤ 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 PTT ≤ 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 all other patients must have normal baseline thyroid function tests
(TSH, T3, T4)

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- 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 should be free of active infection requiring antibiotics (with the exception
of uncomplicated UTI)

- Neuropathy (sensory and motor) less than or equal to CTCAE grade 1

- 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

- No patients with clinically significant cardiovascular disease, including:

- Patients must have blood pressure (BP) no greater than 140 mm Hg (systolic) and
90 mm Hg (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

- 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

- A patient with previous cardiac angioplasty or stenting

- A patient with previous coronary artery bypass graft surgery

- A patient with history of pulmonary embolism, untreated deep venous thrombosis
(DVT), or DVT which has been treated with therapeutic anticoagulation for less
than 6 weeks

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

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

- No patients with active bleeding or pathologic conditions that carry high risk of
bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major

- No 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

- No patients with underlying lesions that caused the fistula or perforation in
the past that have not been corrected

- No 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 disease)

- No history of hemoptysis in excess of 2.5 mL (½ teaspoon ) within 8 weeks prior to
first dose of pazopanib

- No uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection or psychiatric illness/social situations that would limit compliance with
study requirements

- No history of allergic reactions attributed to compounds of similar chemical or
biologic composition to pazopanib

- HIV-positive subjects on combination antiretroviral therapy are ineligible

- No history of coronary artery bypass graft surgery within 6 months prior to

- Patients must have NOT received any non-cytotoxic chemotherapy for management of
recurrent or persistent disease

- Prior hormonal therapy is permitted

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

- No patients who have had prior therapy with pazopanib

- No previous cancer treatment that 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

- 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

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

- 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.

- Any prior radiation therapy must be discontinued at least 4 weeks prior to

- 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)

- Any other prior therapy (chemotherapy) directed at the malignant tumor must be
discontinued at least 3 weeks prior to registration

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

- Strong inhibitors of CYP3A4 are prohibited

- Grapefruit juice is also an inhibitor of CYP450 and should not be taken with

- Strong inducers of CYP3A4 are prohibited

- No history of cardiac angioplasty or stenting within 6 months prior to registration

Type of Study:


Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Progression-free survival (PFS) for at least 6 months

Outcome Description:

Will be characterized with Kaplan-Meier plots and estimates of the median time until death or progression.

Outcome Time Frame:

6 months

Safety Issue:


Principal Investigator

Susana Campos

Investigator Role:

Principal Investigator

Investigator Affiliation:

Gynecologic Oncology Group


United States: Food and Drug Administration

Study ID:




Start Date:

January 2011

Completion Date:

Related Keywords:

  • Recurrent Uterine Sarcoma
  • Uterine Carcinosarcoma
  • Carcinosarcoma
  • Mixed Tumor, Mullerian
  • Uterine Neoplasms
  • Sarcoma



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