Intensity-Modulated Radiation Therapy and Paclitaxel With or Without Pazopanib Hydrochloride in Treating Patients With Anaplastic Thyroid Cancer
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
5 other identifiers
interventional
123
1 country
130
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Oct 2010
Longer than P75 for phase_2
130 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
October 28, 2010
CompletedFirst Submitted
Initial submission to the registry
November 5, 2010
CompletedFirst Posted
Study publicly available on registry
November 8, 2010
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 9, 2020
CompletedResults Posted
Study results publicly available
May 14, 2021
CompletedStudy Completion
Last participant's last visit for all outcomes
May 20, 2022
CompletedJuly 19, 2022
May 1, 2022
9.4 years
November 5, 2010
March 2, 2021
June 28, 2022
Conditions
Outcome Measures
Primary Outcomes (2)
(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.
From randomization to last follow-up.Maximum follow-up for phase II participants at time of analysis was 4.2 years.
(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.
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)
(Phase II) Local-regional Control
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.)
(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]
From start of treatment to last follow-up.Maximum follow-up for phase II participants at time of analysis was 4.2 years.
(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]
From start of treatment to last follow-up.Maximum follow-up for phase II participants at time of analysis was 4.2 years.
(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
2-4 weeks after treatment (approximately week 10-14)
Study Arms (2)
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).
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).
Interventions
Undergo IMRT
Given IV
Given PO
Eligibility Criteria
You may qualify if:
- 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
- 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)
- +10 more criteria
You may not qualify if:
- 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
- +21 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- National Cancer Institute (NCI)lead
- NRG Oncologycollaborator
Study Sites (130)
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, 35233, United States
The Kirklin Clinic at Acton Road
Birmingham, Alabama, 35243, United States
Cancer Center at Saint Joseph's
Phoenix, Arizona, 85004, United States
Saint Joseph's Hospital and Medical Center
Phoenix, Arizona, 85013, United States
Arizona Oncology-Deer Valley Center
Phoenix, Arizona, 85027, United States
Arizona Oncology Services Foundation
Scottsdale, Arizona, 85260, United States
Sutter Cancer Centers Radiation Oncology Services-Auburn
Auburn, California, 95603, United States
Alta Bates Summit Medical Center-Herrick Campus
Berkeley, California, 94704, United States
Mills-Peninsula Medical Center
Burlingame, California, 94010, United States
Sutter Cancer Centers Radiation Oncology Services-Cameron Park
Cameron Park, California, 95682, United States
Eden Hospital Medical Center
Castro Valley, California, 94546, United States
Sutter Cancer Centers Radiation Oncology Services-Roseville
Roseville, California, 95661, United States
Sutter Medical Center Sacramento
Sacramento, California, 95816, United States
California Pacific Medical Center-Pacific Campus
San Francisco, California, 94115, United States
UCSF Medical Center-Mount Zion
San Francisco, California, 94115, United States
UCSF Medical Center-Parnassus
San Francisco, California, 94143, United States
Sutter Cancer Centers Radiation Oncology Services-Vacaville
Vacaville, California, 95687, United States
Sutter Solano Medical Center/Cancer Center
Vallejo, California, 94589, United States
Christiana Gynecologic Oncology LLC
Newark, Delaware, 19713, United States
Delaware Clinical and Laboratory Physicians PA
Newark, Delaware, 19713, United States
Helen F Graham Cancer Center
Newark, Delaware, 19713, United States
Medical Oncology Hematology Consultants PA
Newark, Delaware, 19713, United States
Christiana Care Health System-Christiana Hospital
Newark, Delaware, 19718, United States
Beebe Health Campus
Rehoboth Beach, Delaware, 19971, United States
Christiana Care Health System-Wilmington Hospital
Wilmington, Delaware, 19801, United States
Mayo Clinic in Florida
Jacksonville, Florida, 32224-9980, United States
Moffitt Cancer Center
Tampa, Florida, 33612, United States
Emory University Hospital Midtown
Atlanta, Georgia, 30308, United States
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322, United States
Radiation Oncology Associates PC
Fort Wayne, Indiana, 46804, United States
Parkview Hospital Randallia
Fort Wayne, Indiana, 46805, United States
University of Kansas Cancer Center
Kansas City, Kansas, 66160, United States
The James Graham Brown Cancer Center at University of Louisville
Louisville, Kentucky, 40202, United States
Mary Bird Perkins Cancer Center
Baton Rouge, Louisiana, 70809, United States
Touro Infirmary
New Orleans, Louisiana, 70115, United States
Greater Baltimore Medical Center
Baltimore, Maryland, 21204, United States
Sinai Hospital of Baltimore
Baltimore, Maryland, 21215, United States
Boston Medical Center
Boston, Massachusetts, 02118, United States
Henry Ford Cancer Institute-Downriver
Brownstown, Michigan, 48183, United States
Henry Ford Macomb Hospital-Clinton Township
Clinton Township, Michigan, 48038, United States
Henry Ford Medical Center-Fairlane
Dearborn, Michigan, 48126, United States
Henry Ford Hospital
Detroit, Michigan, 48202, United States
West Michigan Cancer Center
Kalamazoo, Michigan, 49007, United States
Henry Ford Medical Center-Columbus
Novi, Michigan, 48377, United States
Henry Ford West Bloomfield Hospital
West Bloomfield, Michigan, 48322, United States
Fairview Ridges Hospital
Burnsville, Minnesota, 55337, United States
Mercy Hospital
Coon Rapids, Minnesota, 55433, United States
Fairview Southdale Hospital
Edina, Minnesota, 55435, United States
Unity Hospital
Fridley, Minnesota, 55432, United States
Minnesota Oncology Hematology PA-Maplewood
Maplewood, Minnesota, 55109, United States
Abbott-Northwestern Hospital
Minneapolis, Minnesota, 55407, United States
Hennepin County Medical Center
Minneapolis, Minnesota, 55415, United States
North Memorial Medical Health Center
Robbinsdale, Minnesota, 55422, United States
Mayo Clinic in Rochester
Rochester, Minnesota, 55905, United States
Metro Minnesota Community Oncology Research Consortium
Saint Louis Park, Minnesota, 55416, United States
Park Nicollet Clinic - Saint Louis Park
Saint Louis Park, Minnesota, 55416, United States
Regions Hospital
Saint Paul, Minnesota, 55101, United States
United Hospital
Saint Paul, Minnesota, 55102, United States
Ridgeview Medical Center
Waconia, Minnesota, 55387, United States
Rice Memorial Hospital
Willmar, Minnesota, 56201, United States
University of Mississippi Medical Center
Jackson, Mississippi, 39216, United States
Billings Clinic Cancer Center
Billings, Montana, 59101, United States
Memorial Sloan Kettering Basking Ridge
Basking Ridge, New Jersey, 07920, United States
New York-Presbyterian/Brooklyn Methodist Hospital
Brooklyn, New York, 11215, United States
Memorial Sloan Kettering Commack
Commack, New York, 11725, United States
Memorial Sloan Kettering Westchester
Harrison, New York, 10604, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Memorial Sloan Kettering Sleepy Hollow
Sleepy Hollow, New York, 10591, United States
Memorial Sloan Kettering Nassau
Uniondale, New York, 11553, United States
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599, United States
Summa Health System - Akron Campus
Akron, Ohio, 44304, United States
Summa Health System - Barberton Campus
Barberton, Ohio, 44203, United States
University of Cincinnati Cancer Center-UC Medical Center
Cincinnati, Ohio, 45219, United States
Case Western Reserve University
Cleveland, Ohio, 44106, United States
Cleveland Clinic Foundation
Cleveland, Ohio, 44195, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
Mercy Cancer Center-Elyria
Elyria, Ohio, 44035, United States
Summa Health Medina Medical Center
Medina, Ohio, 44256, United States
UH Seidman Cancer Center at Lake Health Mentor Campus
Mentor, Ohio, 44060, United States
UH Seidman Cancer Center at Southwest General Hospital
Middleburg Heights, Ohio, 44130, United States
University Hospitals Parma Medical Center
Parma, Ohio, 44129, United States
UH Seidman Cancer Center at Firelands Regional Medical Center
Sandusky, Ohio, 44870, United States
University of Cincinnati Cancer Center-West Chester
West Chester, Ohio, 45069, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
UPMC-Heritage Valley Health System Beaver
Beaver, Pennsylvania, 15009, United States
UPMC Cancer Centers - Arnold Palmer Pavilion
Greensburg, Pennsylvania, 15601, United States
Penn State Milton S Hershey Medical Center
Hershey, Pennsylvania, 17033-0850, United States
UPMC-Johnstown/John P. Murtha Regional Cancer Center
Johnstown, Pennsylvania, 15901, United States
UPMC Cancer Center at UPMC McKeesport
McKeesport, Pennsylvania, 15132, United States
UPMC-Coraopolis/Heritage Valley Radiation Oncology
Moon Township, Pennsylvania, 15108, United States
UPMC Cancer Center-Natrona Heights
Natrona Heights, Pennsylvania, 15065, United States
UPMC Jameson
New Castle, Pennsylvania, 16105, United States
Thomas Jefferson University Hospital
Philadelphia, Pennsylvania, 19107, United States
UPMC-Presbyterian Hospital
Pittsburgh, Pennsylvania, 15213, United States
UPMC-Saint Margaret
Pittsburgh, Pennsylvania, 15215, United States
UPMC-Shadyside Hospital
Pittsburgh, Pennsylvania, 15232, United States
UPMC Jefferson Regional Radiation Oncology
Pittsburgh, Pennsylvania, 15236, United States
UPMC-Passavant Hospital
Pittsburgh, Pennsylvania, 15237, United States
UPMC-Saint Clair Hospital Cancer Center
Pittsburgh, Pennsylvania, 15243, United States
UPMC Cancer Center at UPMC Northwest
Seneca, Pennsylvania, 16346, United States
UPMC Uniontown Hospital Radiation Oncology
Uniontown, Pennsylvania, 15401, United States
UPMC Washington Hospital Radiation Oncology
Washington, Pennsylvania, 15301, United States
Prisma Health Cancer Institute - Spartanburg
Boiling Springs, South Carolina, 29316, United States
Prisma Health Cancer Institute - Faris
Greenville, South Carolina, 29605, United States
Prisma Health Cancer Institute - Eastside
Greenville, South Carolina, 29615, United States
Prisma Health Cancer Institute - Greer
Greer, South Carolina, 29650, United States
Prisma Health Cancer Institute - Seneca
Seneca, South Carolina, 29672, United States
Parkland Memorial Hospital
Dallas, Texas, 75235, United States
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390, United States
M D Anderson Cancer Center
Houston, Texas, 77030, United States
American Fork Hospital / Huntsman Intermountain Cancer Center
American Fork, Utah, 84003, United States
Sandra L Maxwell Cancer Center
Cedar City, Utah, 84720, United States
Logan Regional Hospital
Logan, Utah, 84321, United States
Intermountain Medical Center
Murray, Utah, 84107, United States
McKay-Dee Hospital Center
Ogden, Utah, 84403, United States
Utah Valley Regional Medical Center
Provo, Utah, 84604, United States
Utah Cancer Specialists-Salt Lake City
Salt Lake City, Utah, 84106, United States
LDS Hospital
Salt Lake City, Utah, 84143, United States
Saint George Regional Medical Center
St. George, Utah, 84770, United States
Sentara Cancer Institute at Sentara CarePlex Hospital
Hampton, Virginia, 23666, United States
Sentara Norfolk General Hospital
Norfolk, Virginia, 23507, United States
Sentara Virginia Beach General Hospital
Virginia Beach, Virginia, 23454, United States
Green Bay Oncology at Saint Vincent Hospital
Green Bay, Wisconsin, 54301-3526, United States
Saint Vincent Hospital Cancer Center Green Bay
Green Bay, Wisconsin, 54301, United States
Green Bay Oncology Limited at Saint Mary's Hospital
Green Bay, Wisconsin, 54303, United States
Saint Vincent Hospital Cancer Center at Saint Mary's
Green Bay, Wisconsin, 54303, United States
University of Wisconsin Carbone Cancer Center
Madison, Wisconsin, 53792, United States
Holy Family Memorial Hospital
Manitowoc, Wisconsin, 54221, United States
Bay Area Medical Center
Marinette, Wisconsin, 54143, United States
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Related Publications (1)
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.
PMID: 36681089DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
One run-in arm was originally planned; more run-in arms added due to amendments to the protocol regimen unrelated to toxicities. In addition, due to higher than projected rates of ineligibility and consent withdrawals, phase II final analysis was amended to be time-driven (3 years of potential follow-up for all eligible phase II participants) instead of event driven (71 deaths of eligible phase II participants), reducing power from 80% (one-sided alpha 0.15) to 77% (one-sided alpha 0.1379),
Results Point of Contact
- Title
- Wendy Seiferheld
- Organization
- NRG Oncology
Study Officials
- PRINCIPAL INVESTIGATOR
Eric J Sherman
NRG Oncology
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 5, 2010
First Posted
November 8, 2010
Study Start
October 28, 2010
Primary Completion
March 9, 2020
Study Completion
May 20, 2022
Last Updated
July 19, 2022
Results First Posted
May 14, 2021
Record last verified: 2022-05