Pazopanib Hydrochloride in Treating Patients With Recurrent or Persistent Uterine Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01247571
First received: November 23, 2010
Last updated: September 16, 2014
Last verified: September 2014
  Purpose

This phase II clinical trial is studying how well pazopanib hydrochloride works in treating patients with recurrent or persistent uterine cancer. 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.


Condition Intervention Phase
Recurrent Uterine Sarcoma
Uterine Carcinosarcoma
Drug: pazopanib hydrochloride
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Evaluation of Pazopanib (NSC # 737754) in the Treatment of Recurrent or Persistent Carcinosarcoma of the Uterus

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Progression-free survival (PFS) for at least 6 months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Will be characterized with Kaplan-Meier plots and estimates of the median time until death or progression.

  • Objective tumor response (complete or partial) [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Adverse events as assessed by CTCAE v4.0 [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
    The numbers of patients with toxicities as assessed by CTCAE v4 will be tabulated by grade and system organ class.

  • PFS and overall survival [ Time Frame: From start of treatment to time of progression or death, assessed up to 5 years ] [ Designated as safety issue: No ]
    Will be characterized with Kaplan-Meier plots and estimates of the median time until death or progression.


Estimated Enrollment: 38
Study Start Date: January 2011
Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (pazopanib hydrochloride)
Patients receive pazopanib hydrochloride PO once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Drug: pazopanib hydrochloride
Given PO
Other Names:
  • GW786034B
  • Votrient

Detailed Description:

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 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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 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 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 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
    • 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 eligible
  • No patients with active bleeding or pathologic conditions that carry high risk of bleeding, such as known bleeding disorder, coagulopathy, or tumor involving major vessels
  • 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 therapy
    • 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 registration
  • 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 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 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 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)
  • 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 pazopanib
  • Strong inducers of CYP3A4 are prohibited
  • No history of cardiac angioplasty or stenting within 6 months prior to registration
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01247571

  Show 41 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Susana Campos Gynecologic Oncology Group
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01247571     History of Changes
Other Study ID Numbers: NCI-2011-02658, NCI-2011-02658, GOG-0230D, CDR0000689585, GOG-0230D, GOG-0230D, U10CA027469
Study First Received: November 23, 2010
Last Updated: September 16, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinosarcoma
Mixed Tumor, Mullerian
Uterine Neoplasms
Genital Diseases, Female
Genital Neoplasms, Female
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Complex and Mixed
Neoplasms, Connective and Soft Tissue
Sarcoma
Urogenital Neoplasms
Uterine Diseases

ClinicalTrials.gov processed this record on October 30, 2014