AzTrials
AzTrials

Thyroid Gland Anaplastic CarcinomaPhase 2NCT01236547

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

A Phase 2 study testing Intensity-Modulated Radiation Therapy, Paclitaxel and Pazopanib Hydrochloride in people with Thyroid Gland Anaplastic Carcinoma, run by National Cancer Institute (NCI) at 130 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Thyroid Gland Anaplastic Carcinoma
What is being tested?
Intensity-Modulated Radiation Therapy, Paclitaxel and Pazopanib Hydrochloride
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
123 participants
Where
130 sitesUnited States
Study dates
28 Oct 2010to 20 May 2022
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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; due to the aggressiveness of this disease, 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
Show all 25Show fewer
  • 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 (within 10 days prior to registration on study)
  • Platelets >= 100,000 cells/mm^3 (within 10 days prior to registration on study)
  • Hemoglobin (Hgb) >= 9.0 g/dl (within 10 days prior to registration on study) (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) (within 10 days prior to registration)
  • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) < 2.5 x institutional ULN (within 10 days prior to registration); 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

Who cannot join

  • 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:
Show all 37Show fewer
  • 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; this exclusion is necessary because the treatment involved in this study may be significantly teratogenic
  • 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 because of the potential for pharmacokinetic interactions with pazopanib; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
  • 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 locations and contacts

130 sites in 1 country.

130 sites in 1 country

United States130 sites

  • Summa Health System - Akron Campus

    Akron, Ohio, 44304

  • American Fork Hospital / Huntsman Intermountain Cancer Center

    American Fork, Utah, 84003

  • Emory University Hospital Midtown

    Atlanta, Georgia, 30308

  • Emory University Hospital/Winship Cancer Institute

    Atlanta, Georgia, 30322

  • Sutter Cancer Centers Radiation Oncology Services-Auburn

    Auburn, California, 95603

  • Greater Baltimore Medical Center

    Baltimore, Maryland, 21204

  • Sinai Hospital of Baltimore

    Baltimore, Maryland, 21215

  • Summa Health System - Barberton Campus

    Barberton, Ohio, 44203

  • Memorial Sloan Kettering Basking Ridge

    Basking Ridge, New Jersey, 07920

  • Mary Bird Perkins Cancer Center

    Baton Rouge, Louisiana, 70809

  • UPMC-Heritage Valley Health System Beaver

    Beaver, Pennsylvania, 15009

  • Alta Bates Summit Medical Center-Herrick Campus

    Berkeley, California, 94704

  • Billings Clinic Cancer Center

    Billings, Montana, 59101

  • University of Alabama at Birmingham Cancer Center

    Birmingham, Alabama, 35233

  • The Kirklin Clinic at Acton Road

    Birmingham, Alabama, 35243

  • Prisma Health Cancer Institute - Spartanburg

    Boiling Springs, South Carolina, 29316

  • Boston Medical Center

    Boston, Massachusetts, 02118

  • New York-Presbyterian/Brooklyn Methodist Hospital

    Brooklyn, New York, 11215

  • Henry Ford Cancer Institute-Downriver

    Brownstown, Michigan, 48183

  • Mills-Peninsula Medical Center

    Burlingame, California, 94010

  • Fairview Ridges Hospital

    Burnsville, Minnesota, 55337

  • Sutter Cancer Centers Radiation Oncology Services-Cameron Park

    Cameron Park, California, 95682

  • Eden Hospital Medical Center

    Castro Valley, California, 94546

  • Sandra L Maxwell Cancer Center

    Cedar City, Utah, 84720

  • UNC Lineberger Comprehensive Cancer Center

    Chapel Hill, North Carolina, 27599

  • University of Cincinnati Cancer Center-UC Medical Center

    Cincinnati, Ohio, 45219

  • Case Western Reserve University

    Cleveland, Ohio, 44106

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Henry Ford Macomb Hospital-Clinton Township

    Clinton Township, Michigan, 48038

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • Memorial Sloan Kettering Commack

    Commack, New York, 11725

  • Mercy Hospital

    Coon Rapids, Minnesota, 55433

  • Parkland Memorial Hospital

    Dallas, Texas, 75235

  • UT Southwestern/Simmons Cancer Center-Dallas

    Dallas, Texas, 75390

  • Henry Ford Medical Center-Fairlane

    Dearborn, Michigan, 48126

  • Henry Ford Hospital

    Detroit, Michigan, 48202

  • Fairview Southdale Hospital

    Edina, Minnesota, 55435

  • Mercy Cancer Center-Elyria

    Elyria, Ohio, 44035

  • Radiation Oncology Associates PC

    Fort Wayne, Indiana, 46804

  • Parkview Hospital Randallia

    Fort Wayne, Indiana, 46805

  • Unity Hospital

    Fridley, Minnesota, 55432

  • Green Bay Oncology at Saint Vincent Hospital

    Green Bay, Wisconsin, 54301-3526

  • Saint Vincent Hospital Cancer Center Green Bay

    Green Bay, Wisconsin, 54301

  • Green Bay Oncology Limited at Saint Mary's Hospital

    Green Bay, Wisconsin, 54303

  • Saint Vincent Hospital Cancer Center at Saint Mary's

    Green Bay, Wisconsin, 54303

  • UPMC Cancer Centers - Arnold Palmer Pavilion

    Greensburg, Pennsylvania, 15601

  • Prisma Health Cancer Institute - Faris

    Greenville, South Carolina, 29605

  • Prisma Health Cancer Institute - Eastside

    Greenville, South Carolina, 29615

  • Prisma Health Cancer Institute - Greer

    Greer, South Carolina, 29650

  • Sentara Cancer Institute at Sentara CarePlex Hospital

    Hampton, Virginia, 23666

  • Memorial Sloan Kettering Westchester

    Harrison, New York, 10604

  • Penn State Milton S Hershey Medical Center

    Hershey, Pennsylvania, 17033-0850

  • M D Anderson Cancer Center

    Houston, Texas, 77030

  • University of Mississippi Medical Center

    Jackson, Mississippi, 39216

  • Mayo Clinic in Florida

    Jacksonville, Florida, 32224-9980

  • UPMC-Johnstown/John P. Murtha Regional Cancer Center

    Johnstown, Pennsylvania, 15901

  • West Michigan Cancer Center

    Kalamazoo, Michigan, 49007

  • University of Kansas Cancer Center

    Kansas City, Kansas, 66160

  • Logan Regional Hospital

    Logan, Utah, 84321

  • The James Graham Brown Cancer Center at University of Louisville

    Louisville, Kentucky, 40202

  • University of Wisconsin Carbone Cancer Center

    Madison, Wisconsin, 53792

  • Holy Family Memorial Hospital

    Manitowoc, Wisconsin, 54221

  • Minnesota Oncology Hematology PA-Maplewood

    Maplewood, Minnesota, 55109

  • Bay Area Medical Center

    Marinette, Wisconsin, 54143

  • UPMC Cancer Center at UPMC McKeesport

    McKeesport, Pennsylvania, 15132

  • Summa Health Medina Medical Center

    Medina, Ohio, 44256

  • UH Seidman Cancer Center at Lake Health Mentor Campus

    Mentor, Ohio, 44060

  • UH Seidman Cancer Center at Southwest General Hospital

    Middleburg Heights, Ohio, 44130

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Abbott-Northwestern Hospital

    Minneapolis, Minnesota, 55407

  • Hennepin County Medical Center

    Minneapolis, Minnesota, 55415

  • UPMC-Coraopolis/Heritage Valley Radiation Oncology

    Moon Township, Pennsylvania, 15108

  • Intermountain Medical Center

    Murray, Utah, 84107

  • UPMC Cancer Center-Natrona Heights

    Natrona Heights, Pennsylvania, 15065

  • UPMC Jameson

    New Castle, Pennsylvania, 16105

  • Touro Infirmary

    New Orleans, Louisiana, 70115

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Christiana Gynecologic Oncology LLC

    Newark, Delaware, 19713

  • Delaware Clinical and Laboratory Physicians PA

    Newark, Delaware, 19713

  • Helen F Graham Cancer Center

    Newark, Delaware, 19713

  • Medical Oncology Hematology Consultants PA

    Newark, Delaware, 19713

  • Christiana Care Health System-Christiana Hospital

    Newark, Delaware, 19718

  • Sentara Norfolk General Hospital

    Norfolk, Virginia, 23507

  • Henry Ford Medical Center-Columbus

    Novi, Michigan, 48377

  • McKay-Dee Hospital Center

    Ogden, Utah, 84403

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • University Hospitals Parma Medical Center

    Parma, Ohio, 44129

  • Thomas Jefferson University Hospital

    Philadelphia, Pennsylvania, 19107

  • Cancer Center at Saint Joseph's

    Phoenix, Arizona, 85004

  • Saint Joseph's Hospital and Medical Center

    Phoenix, Arizona, 85013

  • Arizona Oncology-Deer Valley Center

    Phoenix, Arizona, 85027

  • UPMC-Presbyterian Hospital

    Pittsburgh, Pennsylvania, 15213

  • UPMC-Saint Margaret

    Pittsburgh, Pennsylvania, 15215

  • UPMC-Shadyside Hospital

    Pittsburgh, Pennsylvania, 15232

  • UPMC Jefferson Regional Radiation Oncology

    Pittsburgh, Pennsylvania, 15236

  • UPMC-Passavant Hospital

    Pittsburgh, Pennsylvania, 15237

  • UPMC-Saint Clair Hospital Cancer Center

    Pittsburgh, Pennsylvania, 15243

  • Utah Valley Regional Medical Center

    Provo, Utah, 84604

  • Beebe Health Campus

    Rehoboth Beach, Delaware, 19971

  • North Memorial Medical Health Center

    Robbinsdale, Minnesota, 55422

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

  • Sutter Cancer Centers Radiation Oncology Services-Roseville

    Roseville, California, 95661

  • Sutter Medical Center Sacramento

    Sacramento, California, 95816

  • Metro Minnesota Community Oncology Research Consortium

    Saint Louis Park, Minnesota, 55416

  • Park Nicollet Clinic - Saint Louis Park

    Saint Louis Park, Minnesota, 55416

  • Regions Hospital

    Saint Paul, Minnesota, 55101

  • United Hospital

    Saint Paul, Minnesota, 55102

  • Utah Cancer Specialists-Salt Lake City

    Salt Lake City, Utah, 84106

  • LDS Hospital

    Salt Lake City, Utah, 84143

  • California Pacific Medical Center-Pacific Campus

    San Francisco, California, 94115

  • UCSF Medical Center-Mount Zion

    San Francisco, California, 94115

  • UCSF Medical Center-Parnassus

    San Francisco, California, 94143

  • UH Seidman Cancer Center at Firelands Regional Medical Center

    Sandusky, Ohio, 44870

  • Arizona Oncology Services Foundation

    Scottsdale, Arizona, 85260

  • UPMC Cancer Center at UPMC Northwest

    Seneca, Pennsylvania, 16346

  • Prisma Health Cancer Institute - Seneca

    Seneca, South Carolina, 29672

  • Memorial Sloan Kettering Sleepy Hollow

    Sleepy Hollow, New York, 10591

  • Saint George Regional Medical Center

    St. George, Utah, 84770

  • Moffitt Cancer Center

    Tampa, Florida, 33612

  • Memorial Sloan Kettering Nassau

    Uniondale, New York, 11553

  • UPMC Uniontown Hospital Radiation Oncology

    Uniontown, Pennsylvania, 15401

  • Sutter Cancer Centers Radiation Oncology Services-Vacaville

    Vacaville, California, 95687

  • Sutter Solano Medical Center/Cancer Center

    Vallejo, California, 94589

  • Sentara Virginia Beach General Hospital

    Virginia Beach, Virginia, 23454

  • Ridgeview Medical Center

    Waconia, Minnesota, 55387

  • UPMC Washington Hospital Radiation Oncology

    Washington, Pennsylvania, 15301

  • Henry Ford West Bloomfield Hospital

    West Bloomfield, Michigan, 48322

  • University of Cincinnati Cancer Center-West Chester

    West Chester, Ohio, 45069

  • Rice Memorial Hospital

    Willmar, Minnesota, 56201

  • Christiana Care Health System-Wilmington Hospital

    Wilmington, Delaware, 19801

Other trials in United States

About this study

Official title: 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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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 cycles (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 cycles (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 cycles (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.

Being tested
Intensity-Modulated Radiation Therapy, Paclitaxel, Pazopanib Hydrochloride, Placebo Administration
Medical subject headings
Thyroid Carcinoma, Anaplastic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Intensity-Modulated Radiation TherapyRadiation

    Also called IMRT, Intensity Modulated RT, Intensity-Modulated Radiotherapy, Radiation, Intensity-Modulated Radiotherapy

    Undergo IMRT

  • PaclitaxelDrug

    Also called Anzatax, Asotax, Bristaxol, Praxel

    Given IV

  • Pazopanib HydrochlorideDrug

    Also called GW786034B, Votrient

    Given PO

  • Placebo AdministrationOther

    Given PO

Study groups in NCT01236547
Study groupRoleWhat they receive
Arm I (paclitaxel, pazopanib hydrochloride, IMRT)ExperimentalPatients 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 cycles (for patients with no measurable disease) or continues in the absence of disease progression or unacceptable toxicity (for patients with measurable disease).
Receives: Radiation: Intensity-Modulated Radiation Therapy; Drug: Paclitaxel; Drug: Pazopanib Hydrochloride
Arm II (paclitaxel, placebo, IMRT)Active comparatorPatients 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 cycles (for patients with no measurable disease) or continues in the absence of disease progression or unacceptable toxicity (for patients with measurable disease).
Receives: Radiation: Intensity-Modulated Radiation Therapy; Drug: Paclitaxel; Other: Placebo Administration

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. (Phase II) Overall Survival

    Overall survival time is defined as time from randomization to the date of death (failure) from any cause or last known follow-up (censored). Overall survival rates are estimated by the Kaplan-Meier method. The protocol specifies that the distributions of failure times be compared between the arms, which is reported in the statistical analysis results. One-year rates are provided. Analysis occurred after all eligible participants were potentially followed for 3 years.

    Measured: From randomization to last follow-up.Maximum follow-up for phase II participants at time of analysis was 4.2 years.

  2. (Phase I) Number of Participants With Treatment-related Grade 4 Hemorrhage, Grade 4 Febrile Neutropenia, or Grade 5 Adverse Event (AE), or Discontinuation of Treatment Due to Toxicity [Adverse Events of Concern (AEC)]

    Common Terminology Criteria for AEs (version 4.0) grades AE severity from 1=mild to 5=death. Discontinuation of treatment due to toxicity is defined as < 75% of planned radiation therapy delivered. "Treatment-related" = definitely, probably, or possibly related to treatment. A single run-in arm was originally planned, but additional run-in arms were added due to amendments to the protocol regimen unrelated to toxicities. A two-stage design based on the binomial distribution was used in which the 1st stage analyzes the run-in arm and the 2nd stage analyzes run-in and phase II pazopanib arm participants combined. Because there were multiple run-in arms, only the last is used in the 2nd stage analysis. 1st stage: If ≤4 of 9 participants experience AEC, then conclude treatment is safe. 2nd stage: If ≤8 of 24 participants experience AEC, then conclude treatment safe. Otherwise conclude the treatment is too toxic. Summary data is provided here, see AE Module for specific AE data.

    Measured: From registration to last follow-up. Maximum follow-up for run-in and phase II participants at time of analysis was 7.4 years.

Secondary outcomes (4)

  1. (Phase II) Local-regional Control

    Local-regional failure is defined as local-regional relapse/progression in the thyroid bed or regional lymph nodes. Time to local-regional failure is defined as time from randomization to the date of first local-regional recurrence, last known follow-up (censored), or death without local recurrence (competing risk). Failure rates are estimated using the cumulative incidence method. The protocol specifies 6- and 12-month estimates to be reported and for the full distributions of failure times to be compared between the arms. Analysis occurred after all eligible participants were potentially followed for 3 years.

    Measured: From randomization to last follow-up.Maximum follow-up for phase II participants at time of analysis was 4.2 years. (Statistical analysis compares full distributions therefore all available follow-up was used.)

  2. (Phase II) Percentage of Participants With Treatment-related Grade 4 Hemorrhage, Grade 4 Febrile Neutropenia, or Grade 5 Adverse Event, or Discontinuation of Treatment Due to Toxicity [Adverse Events of Concern]

    Common Terminology Criteria for Adverse Events (CTCAE, v. 4.0) grades adverse event severity from 1=mild to 5=death. Discontinuation of treatment due to toxicity is defined as < 75% of planned radiation therapy delivered. Adverse events rated as definitely, probably, or possibly related to treatment were considered treatment-related. Summary data is provided in this outcome measure.; See Adverse Events Module for specific adverse event data.

    Measured: From start of treatment to last follow-up.Maximum follow-up for phase II participants at time of analysis was 4.2 years.

  3. (Phase II) Percentage of Participants With Treatment-related Grade 3 or 4 Adverse Events Other Than Grade 4 Hemorrhage or Grade 4 Febrile Neutropenia [Not Adverse Events of Concern]

    Common Terminology Criteria for Adverse Events (CTCAE, v. 4.0) grades adverse event severity from 1=mild to 5=death. Adverse events rated as definitely, probably, or possibly related to treatment were considered treatment-related. Summary data is provided in this outcome measure.; See Adverse Events Module for specific adverse event data.

    Measured: From start of treatment to last follow-up.Maximum follow-up for phase II participants at time of analysis was 4.2 years.

  4. (Phase II) Percentage of Participants With Complete or Partial Response of the Primary Site After Chemoradiation Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1

    Complete Response: Disappearance of all target lesions; Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

    Measured: 2-4 weeks after treatment (approximately week 10-14)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Nov 2010 (estimated)
  2. Study start28 Oct 2010
  3. Primary completion9 Mar 2020
  4. Study completion20 May 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
123 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01236547
Sponsor's protocol ID
NCI-2011-02614
Other IDs
NCI-2011-02614, CDR0000688092, RTOG-0912, RTOG-0912, U10CA180868, U10CA021661
Status last verified
May 2022
First submitted
5 Nov 2010
Last updated
19 Jul 2022
Data monitoring committee
Yes

Publications

  • Sherman EJ, Harris J, Bible KC, Xia P, Ghossein RA, Chung CH, Riaz N, Gunn GB, Foote RL, Yom SS, Wong SJ, Koyfman SA, Dzeda MF, Clump DA, Khan SA, Shah MH, Redmond K, Torres-Saavedra PA, Le QT, Lee NY. Radiotherapy and paclitaxel plus pazopanib or placebo in anaplastic thyroid cancer (NRG/RTOG 0912): a randomised, double-blind, placebo-controlled, multicentre, phase 2 trial. Lancet Oncol. 2023 Feb;24(2):175-186. doi: 10.1016/S1470-2045(22)00763-X. Epub 2023 Jan 18.

    PubMed 36681089

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Intensity-Modulated Radiation Therapy, Paclitaxel and Pazopanib Hydrochloride in people with Thyroid Gland Anaplastic Carcinoma, run by National Cancer Institute (NCI) at 130 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 25 inclusion and 37 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 130 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 May 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

(Phase II) Overall Survival (time frame: From randomization to last follow-up.Maximum follow-up for phase II participants at time of analysis was 4.2 years.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01236547, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jul 2022.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in