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A RANDOMIZED PHASE II STUDY OF CONCURRENT INTENSITY MODULATED RADIATION THERAPY (IMRT), PACLITAXEL AND PAZOPANIB (NSC 737754)/PLACEBO, FOR THE TREATMENT OF ANAPLASTIC THYROID CANCER


Phase 2
18 Years
N/A
Not Enrolling
Both
Anaplastic Thyroid Cancer

Thank you

Trial Information

A RANDOMIZED PHASE II STUDY OF CONCURRENT INTENSITY MODULATED RADIATION THERAPY (IMRT), PACLITAXEL AND PAZOPANIB (NSC 737754)/PLACEBO, FOR THE TREATMENT OF ANAPLASTIC THYROID CANCER


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 (Common Terminology Criteria for Adverse Events [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 Response Evaluation Criteria in Solid Tumors
[RECIST]) of the primary site following the treatment component in subjects with measurable
disease prior to chemoradiation. (Phase II component)

OUTLINE:

RUN-IN COMPONENT: Patients receive paclitaxel intravenously (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).

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.


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 (Hgb) >= 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 upper limit of normal (ULN) (except for
patients with Gilbert syndrome and elevations of indirect bilirubin)

- Aspartate aminotransferase (AST) or alanine aminotransferase (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 New York Heart Association (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 electrocardiogram (EKG) abnormalities are ineligible

- No human immunodeficiency virus (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

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Discontinuation of treatment due to toxicity, Grade 4 (CTCAE v. 4.0) hemorrhage, grade 4 febrile neutropenia, or any grade 5 adverse event that is assessed to be definitely, probably, or possibly related to the induction or concurrent treatment

Outcome Time Frame:

Up to 4 years

Safety Issue:

Yes

Principal Investigator

Eric Sherman

Investigator Role:

Principal Investigator

Investigator Affiliation:

Radiation Therapy Oncology Group

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2011-02614

NCT ID:

NCT01236547

Start Date:

October 2010

Completion Date:

Related Keywords:

  • Anaplastic Thyroid Cancer
  • Thyroid Neoplasms
  • Thyroid Diseases

Name

Location

Memorial Sloan Kettering Cancer Center New York, New York  10021
Cleveland Clinic Foundation Cleveland, Ohio  44195
Mayo Clinic Rochester, Minnesota  55905
University of Mississippi Medical Center Jackson, Mississippi  39216-4505
West Michigan Cancer Center Kalamazoo, Michigan  49007-3731
Mary Bird Perkins Cancer Center Baton Rouge, Louisiana  70809
University of Kansas Medical Center Kansas City, Kansas  66160-7353
Boston Medical Center Boston, Massachusetts  02118
McKay-Dee Hospital Center Ogden, Utah  84403
Arthur G. James Cancer Hospital and Solove Research Institute at Ohio State University Medical Center Columbus, Ohio  43210-1240
Arizona Oncology Services Foundation Phoenix, Arizona  85013
Mayo Clinic in Florida Jacksonville, Florida  32224
Case Western Reserve University Cleveland, Ohio  44106
Thomas Jefferson University Hospital Philadelphia, Pennsylvania  19131
M D Anderson Cancer Center Houston, Texas  77030
Froedtert and the Medical College of Wisconsin Milwaukee, Wisconsin  53226
Summa Barberton Hospital Barberton, Ohio  44203
Saint Vincent Hospital Green Bay, Wisconsin  54301
Saint Mary's Hospital Green Bay, Wisconsin  54303
Bay Area Medical Center Marinette, Wisconsin  54143
Lake University Ireland Cancer Center Mentor, Ohio  44060
Intermountain Medical Center Murray, Utah  84157
Utah Valley Regional Medical Center Provo, Utah  84603
Utah Cancer Specialists-Salt Lake City Salt Lake City, Utah  84106
Summa Akron City Hospital Akron, Ohio  44304
Christiana Care Health System-Christiana Hospital Newark, Delaware  19718
UCSF-Mount Zion San Francisco, California  94115
Sentara Hospitals Norfolk, Virginia  23507
The James Graham Brown Cancer Center at University of Louisville Louisville, Kentucky  40202
Sentara Virginia Beach General Hospital Virginia Beach, Virginia  23454