Clinical Trials

Pazopanib Hydrochloride in Treating Patients With Advanced Thyroid Cancer

Location:

Trial status:

Open for Enrollment

Why is this study being done?

PRIMARY OBJECTIVES:

I. To establish the safety and efficacy of pazopanib hydrochloride in patients with differentiated, medullary, or anaplastic thyroid cancer.

SECONDARY OBJECTIVES:

I. To assess the impact of pazopanib hydrochloride on serum and plasma VEGF levels.

II. To explore the potential relationship between changes in thyroglobulin levels and tumor response in patients with advanced differentiated thyroid cancer known to be thyroglobulin antibody negative.

OUTLINE:

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 for 6 months or until 3 years after registration.

Who is eligible to participate?

Inclusion Criteria:

- Histologically or cytologically confirmed thyroid cancer that is now advanced or metastatic disease

- One of the following subtypes:

- Differentiated thyroid cancer

- Absence of sensitivity to therapeutic radioiodine

- Medullary thyroid cancer

- Anaplastic thyroid cancer

- Patients with confirmed differentiated thyroid cancer (DTC) must be thyroglobulin antibody negative to be enrolled in the expanded/additional DTC cohort

- Zero, one or two prior therapeutic regimens (this includes cytotoxic plus non-cytotoxic therapeutic regimens)

- Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral computed tomography (CT) scan

- Objective evidence of tumor progression within the past 6 months, as assessed by the following:

- Unequivocal progression of objectively measured disease on successive appropriate imaging (e.g., CT scan); in cases of uncertainty of tumor progression, the Principal Investigator of the study will be available to assist in decisions

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2 OR Karnofsky PS 60-100%

- Life expectancy > 3 months

- Leukocytes ≥ 3,000/mcL

- Absolute neutrophil count ≥ 1,500/mcL

- Platelets ≥ 100,000/mcL

- Total bilirubin ≤ 1.5 times upper limit of normal (ULN) (direct bilirubin ≤ 1.5 times ULN if patient has Gilbert syndrome)

- Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 2.5 times ULN

- Creatinine ≤ 1.5 times ULN

- Proteinuria ≤ 1+ on urinalysis

- No proteinuria > 1+ (< 30 mg/dL) on two consecutive dipstick or other urine assessments taken at least 1 week apart

- International normalized ratio (INR) ≤ 1.2 times ULN

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception prior to and during study therapy

- Systolic blood pressure (BP) < 140 mm Hg and diastolic BP < 90 mm Hg

- Initiation or adjustment of BP medication is permitted prior to registration provided the average of three BP readings at a visit prior to registration is < 140/90 mm Hg

- No sensitivity to therapeutic radioiodine (differentiated only)

- Able to understand and willing to sign a written informed consent document

- Willing to comply with the requirements of the study

- Willing to donate blood for correlative marker studies (only applicable to sites within the United States)

- No admission for unstable angina, cardiac angioplasty, or stenting within the past 12 weeks

- At least 4 weeks since prior radiotherapy

- At least 4 weeks since prior major surgery

- No prior surgical procedure affecting absorption

- No requirement for IV alimentation

- No prior radiotherapy to ≥ 25% of bone marrow

- No concurrent octreotide

- Concurrent octreotide allowed provided tumor progression on this drug has been demonstrated

- No other concurrent investigational agents

- No cytochrome (CYP) interactive medications prior to, during, and for at least 1-2 weeks after discontinuation from the study

- No concurrent antiretroviral therapy for human immunodeficiency virus (HIV)-positive patients

- No concurrent medications or substances known to affect or with the potential to affect the activity or pharmacokinetics of pazopanib hydrochloride

- No concurrent investigational or commercial agents or therapies other than those used for this study with the intent to treat the patient's malignancy

- No concurrent therapeutic warfarin

- Low molecular weigh the paring and prophylactic low-dose warfarin allowed

- No more than 2 total prior cytotoxic or noncytotoxic therapeutic regimens

- Up to two total prior noncytotoxic or cytotoxic therapeutic regimens are allowed provided therapy ceased > 21 days prior to registration

- No concurrent medications that are associated with a risk of QTc prolongation and/or Torsades de Pointes

Exclusion Criteria:

- Thyroid lymphomas, sarcomas, or metastatic disease from other sites of origin to thyroid

- Disease that is measurable by physical examination only

- Known active and/or untreated brain metastases and/or brain metastases requiring ongoing therapy (e.g., corticosteroids)

- History of allergic reactions attributed to compounds of similar chemical or biologic composition to pazopanib hydrochloride or other agents used in the study

- QTc prolongation (defined as a QTc interval ≥ 4800 msecs) or other significant electrocardiogram (ECG) abnormalities (e.g., frequent ventricular ectopy or evidence of ongoing myocardial ischemia); NOTE: the Principal Investigator of the study should be contacted in the event of uncertainty related patient eligibility based upon ECG changes

- Any condition that impairs the ability to swallow and retain pazopanib hydrochloride, including any of the following:

- Gastrointestinal tract disease resulting in an inability to take oral medication

- Active peptic ulcer disease

- Any of the following conditions:

- Serious or nonhealing wound, ulcer, or bone fracture

- History of abdominal fistula

- Gastrointestinal perforation

- Active diverticulitis

- Intra-abdominal abscess or gastrointestinal tract bleeding within the past 28 days prior to registration

- History of cerebrovascular accident (CVA) within the past 6 months

- History of myocardial infarction, cardiac arrhythmia within the past 12 weeks

- History of venous thrombosis within the past 12 weeks

- NYHA class III or IV heart failure

- History of bleeding disorder including hemophilia, disseminated intravascular coagulation, or any other abnormality of coagulation potentially predisposing patients to bleeding

- Poorly controlled depression or anxiety disorder, or recent (≤ 6 months)suicidal ideation

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would or might reasonably be expected to limit compliance with study requirements

Last updated: 04/01/2013

NCT ID: NCT00625846

IRB Number:07-004057