Intensity-Modulated Radiation Therapy and Paclitaxel with or without Pazopanib Hydrochloride in Treating Patients with Anaplastic Thyroid Cancer

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Basic Trial Information

PhaseTypeStatusAgeTrial IDs
Phase IIBiomarker/Laboratory analysis, TreatmentActive18 and overRTOG-0912
NCI-2011-02614, CDR0000688092, NCT01236547

Trial Description

Summary

This randomized phase II trial studies the side effects and how well intensity-modulated radiation therapy (IMRT) and paclitaxel 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, by stopping them from dividing, or by stopping them from spreading. 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 radiation therapy and paclitaxel are more effective when given with pazopanib hydrochloride in treating thyroid cancer.

Further Study Information

PRIMARY OBJECTIVES:

I. To evaluate the safety of IMRT, paclitaxel, and pazopanib (pazopanib hydrochloride) suspension. (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 version 4.0 [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 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 pazopanib hydrochloride orally (PO) once daily (QD) for 2-3 weeks. Patients then receive concurrent paclitaxel IV over 1 hour once weekly and pazopanib hydrochloride PO QD for 6-7 weeks (or until radiation treatment is completed) 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 pazopanib hydrochloride PO QD. 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 pazopanib hydrochloride PO QD for 2-3 weeks. Patients then receive concurrent paclitaxel IV over 1 hour once weekly and pazopanib hydrochloride PO QD for 6-7 weeks (or until radiation treatment is completed) 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 pazopanib hydrochloride PO QD. 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 placebo PO QD for 2-3 weeks. Patients then receive concurrent paclitaxel IV over 1 hour once weekly and placebo PO QD for 6-7 weeks (or until radiation treatment is completed) 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 placebo PO QD. 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.

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)

Note: tissue collection for central review is mandatory, but central review is not required for eligibility; treatment will be started prior to central review

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

The following minimum diagnostic workup is required:

History/physical examination within 2 weeks prior to registration

Imaging of neck and brain (computed tomography [CT] scan or magnetic resonance imaging [MRI]) and chest/abdominal imaging (chest x-ray or chest CT scan, or full body positron emission tomography [PET]/CT are acceptable) within 4 weeks prior to registration

Note: the CT scan of the neck must be done with contrast or if an MRI is done, with gadolinium; therefore, the CT portion of a full body PET/CT has to be a high resolution CT to be acceptable for eligibility

Abdominal imaging must cover the liver and adrenal glands; therefore, separate imaging is not required if these areas are covered by a chest CT scan

Electrocardiogram within 10 days prior to registration

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 (Note: 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's syndrome and elevations of indirect bilirubin)

Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2.5 x institutional ULN ; note: patients who have both bilirubin > ULN and AST/ALT > ULN are not eligible (unless they have Gilbert's 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 within 10 days prior to registration; Note: if neither criteria is met, the creatinine clearance must be > 50 mL/min/1.73 m^2 per either the Cockcroft-Gault equation, Jeliffe method, or 12- or 24-hour urine collection

Serum electrolytes including sodium, potassium, blood urea nitrogen (BUN), creatinine, glucose, magnesium, phosphate, and calcium within 10 days prior to registration

Documentation of the patient’s history of corrected QT interval (QTc) prolongation, family history of prolonged QTc, and relevant cardiac disease within 10 days prior to registration

Evaluation of the patient’s medications within 10 days prior to registration with attempt to change any medication that affects cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4)

Blood pressure =< 140/90 within 10 days of registration (must be taken and recorded by a health care professional); Note: 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, and the treating physician must believe that this is feasible in order to enroll the patient

Prothrombin time (PT)/international normalized ratio (INR)/partial thromboplastin time (PTT) within 1.2 x the upper limit of normal within 10 days prior to registration unless the patient is receiving coumadin and has a stable INR that is in range for the desired level of anticoagulation

Negative pregnancy test (serum or urine) within 10 days of registration in women of child-bearing potential

Women of childbearing potential and male participants who are sexually active must agree to practice adequate contraception during treatment and for 6 months post-treatment

The patient must provide study specific informed consent prior to study entry

Exclusion Criteria:

Known active invasive malignancy (except for non-melanomatous skin cancer or anaplastic thyroid cancer; the presence of prostate cancer confined to the prostate with a prostate-specific antigen [PSA] =< 1 ng/mL for more than 6 months also is allowed)

Prior systemic chemotherapy for anaplastic thyroid cancer

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

Patients receiving other investigational agents

Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields

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

Myocardial Infarction

Cardiac angioplasty or stenting

Coronary artery bypass graft surgery

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

Arterial thrombosis

Symptomatic peripheral vascular disease

Class III or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system; Note: a patient who has a history of class III heart failure and is asymptomatic on treatment may be considered eligible for the study

Certain medications that are associated with a risk for QTc prolongation and/or torsades de pointes, although not prohibited, should be avoided or replaced with medications that do not carry these risks, if possible

Patients who require heparin (other than low-molecular weight heparin)

Patients with any condition that may impair the ability to absorb oral medications/investigational product including:

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

Active peptic ulcer disease

Malabsorption syndrome

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's disease) or other gastrointestinal conditions which increase the risk of perforation

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

History of hemoptysis within 30 days of registration; Note: patients who have minimal bleeding from the mouth, which 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

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

Pregnancy or women of childbearing potential and men who are sexually active and not willing/able to use medically acceptable forms of contraception

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

QTc prolongation defined as a QTc interval >= 480 msecs or other significant electrocardiogram (EKG) abnormalities are ineligible; Note: if unsure about EKG abnormality, the treating physician should discuss this with Drs. Sherman or Bible

Known brain metastasis

Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy

Certain medications that act through the cytochrome P450 (CYP450) system are specifically prohibited in patients receiving pazopanib and others should be avoided or administered with extreme caution

Strong inhibitors of CYP3A4 such as ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole may increase pazopanib concentrations and are prohibited; although, in exceptional circumstances, they may be administered in conjunction with lowering the dose of pazopanib by 50% of what would otherwise be administered; grapefruit juice is also an inhibitor of CYP450 and should not be taken with pazopanib

Strong inducers of CYP3A4, such as rifampin, may decrease pazopanib concentrations, are strictly prohibited

Medications that have narrow therapeutic windows and are substrates of CYP3A4, cytochrome P450, family 2, subfamily D, polypeptide 6 (CYP2D6), or cytochrome P450, family 2, subfamily C, polypeptide 8 (CYP2C8) should be avoided and, if necessary, administered with caution

Trial Contact Information

Trial Lead Organizations / Sponsors / Collaborators

National Cancer Institute

  • National Cancer Institute
Eric Jeffrey Sherman, Principal Investigator

Trial Sites

U.S.A.

Alabama
Birmingham

The Kirklin Clinic at Acton Road

Sharon A. Spencer
Ph: 205-934-0309

Sharon A. Spencer
Principal Investigator

University of Alabama at Birmingham Cancer Center

Sharon A. Spencer
Ph: 205-934-0309

Sharon A. Spencer
Principal Investigator

Arizona
Phoenix

University of Arizona Cancer Center at Saint Joseph's

David G. Brachman
Ph: 877-602-4111
Email: david.brachman@dignityhealth.org

David G. Brachman
Principal Investigator

California
Auburn

Sutter Cancer Centers Radiation Oncology Services-Auburn

Christopher Uwe Jones
Ph: 916-454-6618
Email: bernicl@sutterhealth.org

Christopher Uwe Jones
Principal Investigator

Cameron Park

Sutter Cancer Centers Radiation Oncology Services-Cameron Park

Christopher Uwe Jones
Ph: 916-454-6618
Email: bernicl@sutterhealth.org

Christopher Uwe Jones
Principal Investigator

Roseville

Sutter Cancer Centers Radiation Oncology Services-Roseville

Christopher Uwe Jones
Ph: 916-454-6618
Email: bernicl@sutterhealth.org

Christopher Uwe Jones
Principal Investigator

Sacramento

Sutter General Hospital

Christopher Uwe Jones
Ph: 916-454-6618
Email: bernicl@sutterhealth.org

Christopher Uwe Jones
Principal Investigator

Vacaville

Sutter Cancer Centers Radiation Oncology Services-Vacaville

Christopher Uwe Jones
Ph: 916-454-6618
Email: bernicl@sutterhealth.org

Christopher Uwe Jones
Principal Investigator

Delaware
Newark

Christiana Care Health System-Christiana Hospital

Adam Raben
Ph: 302-733-6227

Adam Raben
Principal Investigator

Florida
Jacksonville

Mayo Clinic in Florida

Robert L. Foote
Ph: 507-284-0079
Email: foote.robert@mayo.edu

Robert L. Foote
Principal Investigator

Tampa

Moffitt Cancer Center

Jimmy J. Caudell
Ph: 800-456-7121
Email: canceranswers@moffitt.org

Jimmy J. Caudell
Principal Investigator

Georgia
Atlanta

Emory University Hospital Midtown

Kristin Ann Higgins
Ph: 404-778-1868

Kristin Ann Higgins
Principal Investigator

Emory University/Winship Cancer Institute

Kristin Ann Higgins
Ph: 404-778-1868

Kristin Ann Higgins
Principal Investigator

Indiana
Fort Wayne

Parkview Hospital Randallia

Brian K. Chang
Ph: 260-373-8888
Email: parkviewresearch@parkview.com

Brian K. Chang
Principal Investigator

Radiation Oncology Associates PC

Brian K. Chang
Ph: 260-373-8888
Email: parkviewresearch@parkview.com

Brian K. Chang
Principal Investigator

Maryland
Baltimore

Greater Baltimore Medical Center

Geoffrey Alexander Neuner
Ph: 443-849-3706

Geoffrey Alexander Neuner
Principal Investigator

Massachusetts
Boston

Boston Medical Center

Minh Tam Truong
Ph: 617-638-7037
Email: minh-tam.truong@bmc.org

Minh Tam Truong
Principal Investigator

Michigan
Detroit

Henry Ford Hospital

Eleanor M. Walker
Ph: 313-916-1784

Eleanor M. Walker
Principal Investigator

Minnesota
Rochester

Mayo Clinic

Robert L. Foote
Ph: 507-284-0079
Email: foote.robert@mayo.edu

Robert L. Foote
Principal Investigator

Saint Paul

Regions Hospital

Paul W. Sperduto
Ph: 952-442-7851
Email: MMCCOP@parknicollet.com

Paul W. Sperduto
Principal Investigator

Mississippi
Jackson

University of Mississippi Medical Center

Shankar P. G. Giri
Ph: 601-815-6700

Shankar P. G. Giri
Principal Investigator

New Jersey
Basking Ridge

Memorial Sloan Kettering Cancer Center at Basking Ridge

Eric Jeffrey Sherman
Ph: 212-639-7202

Eric Jeffrey Sherman
Principal Investigator

New York
Brooklyn

The New York Methodist Hospital

Krishnamurthi Sundaram
Ph: 718-270-8216
Email: sima.terebelo@downstate.edu

Krishnamurthi Sundaram
Principal Investigator

Commack

Memorial Sloan Kettering Cancer Center Commack

Eric Jeffrey Sherman
Ph: 212-639-7202

Eric Jeffrey Sherman
Principal Investigator

New York

Memorial Sloan-Kettering Cancer Center

Eric Jeffrey Sherman
Ph: 212-639-7202

Eric Jeffrey Sherman
Principal Investigator

Rockville Centre

Memorial Sloan-Kettering Cancer Center Rockville Centre

Eric Jeffrey Sherman
Ph: 212-639-7202

Eric Jeffrey Sherman
Principal Investigator

Sleepy Hollow

Memorial Sloan-Kettering Cancer Center Sleepy Hollow

Eric Jeffrey Sherman
Ph: 212-639-7202

Eric Jeffrey Sherman
Principal Investigator

West Harrison

Memorial Sloan-Kettering Cancer Center West Harrison

Eric Jeffrey Sherman
Ph: 212-639-7202

Eric Jeffrey Sherman
Principal Investigator

North Carolina
Chapel Hill

UNC Lineberger Comprehensive Cancer Center

Bhishamjit S. Chera
Ph: 877-668-0683
Email: cancerclinicaltrials@med.unc.edu

Bhishamjit S. Chera
Principal Investigator

Ohio
Cincinnati

University of Cincinnati

Kevin Patrick Redmond
Ph: 513-558-4553
Email: uchealthnews@uc.edu

Kevin Patrick Redmond
Principal Investigator

Cleveland

Cleveland Clinic Foundation

David J. Adelstein
Ph: 866-223-8100

David J. Adelstein
Principal Investigator

Columbus

Ohio State University Comprehensive Cancer Center

Manisha H. Shah
Ph: 614-293-7529
Email: Jamesline@osumc.edu

Manisha H. Shah
Principal Investigator

West Chester

University Pointe

Kevin Patrick Redmond
Ph: 513-558-4553
Email: uchealthnews@uc.edu

Kevin Patrick Redmond
Principal Investigator

Oklahoma
Oklahoma City

University of Oklahoma Health Sciences Center

Terence S. Herman
Ph: 405-271-8777
Email: ou-clinical-trials@ouhsc.edu

Terence S. Herman
Principal Investigator

Pennsylvania
Greensburg

UPMC Cancer Centers - Arnold Palmer Pavilion

James Paul Ohr
Ph: 412-235-1030
Email: ohrj@umpc.edu

James Paul Ohr
Principal Investigator

Moon Township

UPMC-Coraopolis/Heritage Valley Radiation Oncology

James Paul Ohr
Ph: 412-235-1030
Email: ohrj@umpc.edu

James Paul Ohr
Principal Investigator

Philadelphia

Thomas Jefferson University Hospital

Jennifer Maria Johnson
Ph: 215-955-6084

Jennifer Maria Johnson
Principal Investigator

Pittsburgh

UPMC Jefferson Regional Radiation Oncology

James Paul Ohr
Ph: 412-235-1030
Email: ohrj@umpc.edu

James Paul Ohr
Principal Investigator

UPMC-Passavant Hospital

James Paul Ohr
Ph: 412-235-1030
Email: ohrj@umpc.edu

James Paul Ohr
Principal Investigator

UPMC-Saint Clair Hospital Cancer Center

James Paul Ohr
Ph: 412-235-1030
Email: ohrj@umpc.edu

James Paul Ohr
Principal Investigator

UPMC-Saint Margaret

James Paul Ohr
Ph: 412-235-1030
Email: ohrj@umpc.edu

James Paul Ohr
Principal Investigator

UPMC-Shadyside Hospital

James Paul Ohr
Ph: 412-235-1030
Email: ohrj@umpc.edu

James Paul Ohr
Principal Investigator

South Carolina
Greenville

Greenville Health System Cancer Institute-Eastside

David Lawrence Grisell
Ph: 864-241-6251

David Lawrence Grisell
Principal Investigator

Greenville Health System Cancer Institute-Faris

David Lawrence Grisell
Ph: 864-241-6251

David Lawrence Grisell
Principal Investigator

Greer

Greenville Health System Cancer Institute-Greer

David Lawrence Grisell
Ph: 864-241-6251

David Lawrence Grisell
Principal Investigator

Seneca

Greenville Health System Cancer Institute-Seneca

David Lawrence Grisell
Ph: 864-241-6251

David Lawrence Grisell
Principal Investigator

Spartanburg

Greenville Health System Cancer Institute-Spartanburg

David Lawrence Grisell
Ph: 864-241-6251

David Lawrence Grisell
Principal Investigator

Utah
American Fork

American Fork Hospital / Huntsman Intermountain Cancer Center

Vilija N. Avizonis
Ph: 801-507-3810
Email: vilija.avizonis@imail.org

Vilija N. Avizonis
Principal Investigator

Logan

Logan Regional Hospital

Vilija N. Avizonis
Ph: 801-507-3810
Email: vilija.avizonis@imail.org

Vilija N. Avizonis
Principal Investigator

Murray

Intermountain Medical Center

Vilija N. Avizonis
Ph: 801-507-3810
Email: vilija.avizonis@imail.org

Vilija N. Avizonis
Principal Investigator

Ogden

McKay-Dee Hospital Center

Vilija N. Avizonis
Ph: 801-507-3810
Email: vilija.avizonis@imail.org

Vilija N. Avizonis
Principal Investigator

Provo

Utah Valley Regional Medical Center

Vilija N. Avizonis
Ph: 801-507-3810
Email: vilija.avizonis@imail.org

Vilija N. Avizonis
Principal Investigator

Saint George

Dixie Medical Center Regional Cancer Center

Vilija N. Avizonis
Ph: 801-507-3810
Email: vilija.avizonis@imail.org

Vilija N. Avizonis
Principal Investigator

Salt Lake City

Utah Cancer Specialists-Salt Lake City

Vilija N. Avizonis
Ph: 801-507-3810
Email: vilija.avizonis@imail.org

Vilija N. Avizonis
Principal Investigator

Virginia
Hampton

Sentara Cancer Institute at Sentara CarePlex Hospital

Scott S. Williams
Ph: 757-388-2406

Scott S. Williams
Principal Investigator

Norfolk

Sentara Hospitals

Scott S. Williams
Ph: 757-388-2406

Scott S. Williams
Principal Investigator

Virginia Beach

Sentara Virginia Beach General Hospital

Scott S. Williams
Ph: 757-388-2406

Scott S. Williams
Principal Investigator

Wisconsin
Green Bay

Saint Mary's Hospital

James L. Leenstra
Ph: 507-645-2655

James L. Leenstra
Principal Investigator

Saint Vincent Hospital

James L. Leenstra
Ph: 507-645-2655

James L. Leenstra
Principal Investigator

Madison

University of Wisconsin Hospital and Clinics

Randall J. Kimple
Ph: 608-262-7224
Email: rkimple@humonc.wisc.edu

Randall J. Kimple
Principal Investigator

Milwaukee

Froedtert and the Medical College of Wisconsin

Christopher J. Schultz
Ph: 414-805-4380
Email: cschultz@mcw.edu

Christopher J. Schultz
Principal Investigator

Link to the current ClinicalTrials.gov record.
NLM Identifier NCT01236547

Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.