Basic Trial Information
Trial Description
     Summary
     Further Trial Information
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Trial Description

Summary

This randomized phase II trial is studying the side effects and how well giving intensity-modulated radiation therapy and paclitaxel together with or without pazopanib hydrochloride works in treating patients with anaplastic thyroid cancer. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue. Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether giving radiation therapy and paclitaxel together is more effective with pazopanib hydrochloride in treating thyroid cancer

Further Study Information

PRIMARY OBJECTIVES:

I. To evaluate the safety of IMRT, paclitaxel, and pazopanib. (Run-in component) II. To evaluate and compare overall survival at 1 year from study registration. (Phase II component)

SECONDARY OBJECTIVES:

I. To evaluate local-regional control at 6 and 12 months. (Phase II component) II. To evaluate the rate of grade 4 (CTCAE, v. 4.0) hemorrhage, grade 4 febrile neutropenia, or any grade 5 adverse event assessed to be definitely, probably, or possibly related to the induction or concurrent treatment components of the protocol regimen. (Phase II component) III. To evaluate the rates of other adverse events (CTCAE, v. 4.0) assessed to be definitely, probably, or possibly related to the induction or concurrent treatment components of the protocol regimen. (Phase II component) IV. To evaluate the rate of treatment discontinuation due to toxicity during the induction or concurrent treatment components of the protocol regimen. (Phase II component) V. To evaluate the rate of grade 4 (CTCAE, v. 4.0) hemorrhage or any grade 5 adverse event assessed to be definitely, probably, or possibly related to adjuvant paclitaxel or pazopanib/placebo after concurrent treatment. (Phase II component) VI. To evaluate the rates of other adverse events (CTCAE, v. 4.0) assessed to be definitely, probably, or possibly related to adjuvant paclitaxel or pazopanib/placebo after concurrent treatment. (Phase II component) VII. To evaluate response (as per RECIST) of the primary site following the treatment component in subjects with measurable disease prior to chemoradiation. (Phase II component)

OUTLINE: This is a multicenter study.

RUN-IN COMPONENT: Patients receive paclitaxel IV over 1 hour once weekly and oral pazopanib hydrochloride once daily for 2-3 weeks. Patients then receive concurrent paclitaxel IV over 1 hour once weekly and oral pazopanib hydrochloride once daily for 6 weeks and intensity-modulated radiotherapy (IMRT) 5 days per week for 6.5 weeks (total of 66 Gy in 33 fractions). Beginning 25-31 days after the completion of IMRT, patients receive paclitaxel IV over 1 hour once weekly and oral pazopanib hydrochloride once daily. Treatment repeats every 3 weeks for 4 courses (for patients with no measurable disease) or continues in the absence of disease progression or unacceptable toxicity (for patients with measurable disease).

RANDOMIZED PHASE II COMPONENT: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive paclitaxel IV over 1 hour once weekly and oral pazopanib hydrochloride once daily for 2-3 weeks. Patients then receive concurrent paclitaxel IV over 1 hour once weekly and oral pazopanib hydrochloride once daily for 6 weeks and IMRT 5 days per week for 6.5 weeks (total of 66 Gy in 33 fractions). Beginning 25-31 days after the completion of IMRT, patients receive paclitaxel IV over 1 hour once weekly and oral pazopanib hydrochloride once daily. Treatment repeats every 3 weeks for 4 courses (for patients with no measurable disease) or continues in the absence of disease progression or unacceptable toxicity (for patients with measurable disease).

ARM II: Patients receive paclitaxel IV over 1 hour once weekly and oral placebo once daily for 2-3 weeks. Patients then receive concurrent paclitaxel IV over 1 hour once weekly and oral placebo once daily for 6 weeks and IMRT 5 days per week for 6.5 weeks (total of 66 Gy in 33 fractions). Beginning 25-31 days after the completion of IMRT, patients receive paclitaxel IV over 1 hour once weekly and oral placebo once daily. Treatment repeats every 3 weeks for 4 courses (for patients with no measurable disease) or continues in the absence of disease progression or unacceptable toxicity (for patients with measurable disease).

Tissue samples may be collected for correlative studies. After completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 1 year, and then annually thereafter.

Eligibility Criteria

Inclusion Criteria:

• Pathologically (histologically or cytologically) proven* diagnosis of anaplastic thyroid cancer (a diagnosis that is noted to be "consistent with anaplastic thyroid cancer" with the presence of a thyroid mass is acceptable)

• If there was a total or partial thyroidectomy completed within 3 months of enrollment, the surgical specimen must show the area of anaplastic thyroid cancer to be at least 1 cm in greatest dimension

• No known brain metastases

• Zubrod performance status 0-2

• Absolute neutrophil count (ANC) ≥ 1,500 cells/mm^3

• Platelets ≥ 100,000 cells/mm^3

• Hemoglobin ≥ 9.0 g/dL (the use of transfusion or other intervention to achieve Hgb ≥ 9.0 g/dL is acceptable)

• Total bilirubin < 1.5 x institutional ULN (except for patients with Gilbert syndrome and elevations of indirect bilirubin)

• AST or ALT < 2.5 x institutional ULN (patients who have both bilirubin > ULN and AST/ALT > ULN are not eligible unless they have Gilbert syndrome and elevations of indirect bilirubin)

• Spot urine protein to creatinine ratio (UPCR) < 1 or a 24-hour urine protein collection < 1 gm) within 10 days prior to registration

• Creatinine < 1.5 mg/dL or within normal institutional limits (if neither criteria is met, the creatinine clearance must be > 50 mL/min^2 per either the Cockcroft-Gault equation, Jeliffe method, or 12- or 24-hour urine collection)

• Documentation of the patient's history of QTc prolongation, family history of prolonged QTc, and relevant cardiac disease

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use adequate contraception during and for at least 6 months of completing study therapy

• Blood pressure < 140/90 within 10 days of registration (must be taken and recorded by a health care professional)

• If the systolic blood pressure is > 140 and/or diastolic blood pressure is > 90 at the time of registration, the patient's blood pressure must be controlled

• Systolic blood pressure must be < 140 and diastolic blood pressure must be < 90 on at least 2 separate measurements prior to the start of treatment

• The treating physician must believe that this is feasible in order to enroll the patient

• No known active invasive malignancy (except for nonmelanomatous skin cancer, differentiated thyroid cancer, or the presence of prostate cancer confined to the prostate with a PSA < 1 ng/mL for more than 6 months)

• No patients with any of the following cardiovascular conditions within the past 6 months:

• Cerebrovascular accident (CVA) or transient ischemic attack (TIA)

• Admission for unstable angina

• Cardiac angioplasty or stenting

• Coronary artery bypass graft surgery

• Pulmonary embolism, untreated deep venous thrombosis (DVT), or DVT that has been treated with therapeutic anticoagulation for less than 6 weeks

• Arterial thrombosis

• Symptomatic peripheral vascular disease

• Class II-IV heart failure as defined by the NYHA functional classification system (a patient who has a history of class II heart failure and is asymptomatic on treatment may be considered eligible for the study)

• Patients with an arrhythmia are excluded

• Patients with atrial fibrillation, supraventricular tachycardia, or bradycardia are eligible but these conditions must be well controlled with medication or a pacemaker

• No patients with any condition that may impair the ability to swallow or absorb oral medications/investigational product including:

• Any lesion, whether induced by tumor, radiation, or other conditions, that makes it difficult to swallow capsules or pills

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

• Active peptic ulcer disease

• Malabsorption syndrome

• No patients with any condition that may increase the risk of gastrointestinal bleeding or gastrointestinal perforation, including:

• Active peptic ulcer disease

• Known intraluminal metastatic lesions

• Inflammatory bowel disease (e.g., ulcerative colitis, Crohn disease) or other gastrointestinal conditions that increase the risk of perforation

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

• No history of hemoptysis within 30 days of registration

• Patients who have minimal bleeding from the mouth that is clearly not related to a source in the lungs (i.e., surgery such as a non-lung biopsy) are eligible only after good hemostasis has been documented

• 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 prior allergic reaction to the study drug(s) involved in this protocol

• Patients with QTc prolongation defined as a QTc interval > 480 msecs or other significant EKG abnormalities are ineligible

• No HIV-positive patients on combination antiretroviral therapy

• No concurrent St. John wort

• No prior systemic chemotherapy for anaplastic thyroid cancer

• No patients who have had chemotherapy or radiotherapy within 4 weeks of registration (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered > 4 weeks previously

• No patients receiving other investigational agents

• No prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields

• No patients who require heparin (other than low-molecular weight heparin)

• Strong inducers of CYP3A4, such as rifampin, are strictly prohibited

• Strong inhibitors of CYP3A4, including grapefruit juice, are prohibited

Trial Contact Information

Trial Lead Organizations/Sponsors

National Cancer Institute

Eric Sherman

Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01236547
Information obtained from ClinicalTrials.gov on January 07, 2013

Back to Top