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

This study has suspended participant recruitment.
(Temporarily Closed to Accrual)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01236547
First received: November 5, 2010
Last updated: February 7, 2014
Last verified: February 2014

November 5, 2010
February 7, 2014
October 2010
December 2019   (final data collection date for primary 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 [ Time Frame: Up to 4 years ] [ Designated as safety issue: Yes ]
  • Overall survival (OS) (Phase II) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Estimated using the Kaplan-Meier method.
  • Grade 4 (CTCAE, v. 4.0) hemorrhage, grade 4 febrile neutropenia, discontinuation of treatment due to toxicity, or any grade 5 adverse event that is definitely not related to disease progression) (Run-in) [ Designated as safety issue: Yes ]
  • Overall survival (OS) at 1 year from study registration (Phase II) [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01236547 on ClinicalTrials.gov Archive Site
  • Local-regional control (Phase II) [ Time Frame: Up to 12 months ] [ Designated as safety issue: No ]
    Estimated by the cumulative incidence method.
  • Grade 4 (CTCAE, v. 4.0) hemorrhage, grade 4 febrile neutropenia, discontinuation of treatment due to toxicity, or any grade 5 adverse event (Phase II) [ Time Frame: Up to 4 years ] [ Designated as safety issue: Yes ]
    Only adverse events (AEs) assessed to be definitely, probably, or possibly related to protocol treatment will be considered. The rates of adverse events, discontinuation of treatment, and response will be estimated using a binomial distribution along with their associated 95% confidence intervals and will be compared using Fisher's exact test.
  • 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) [ Time Frame: Not Provided ] [ Designated as safety issue: Yes ]
    Only adverse events (AEs) assessed to be definitely, probably, or possibly related to protocol treatment will be considered. The rates of adverse events, discontinuation of treatment, and response will be estimated using a binomial distribution along with their associated 95% confidence intervals and will be compared using Fisher's exact test.
  • Grade 4 (CTCAE, v. 4.0) hemorrhage or any grade 5 adverse event related to adjuvant paclitaxel or pazopanib hydrochloride/placebo after concurrent treatment (Phase II) [ Time Frame: Up to 4 years ] [ Designated as safety issue: Yes ]
    Only adverse events (AEs) assessed to be definitely, probably, or possibly related to protocol treatment will be considered. The rates of adverse events, discontinuation of treatment, and response will be estimated using a binomial distribution along with their associated 95% confidence intervals and will be compared using Fisher's exact test.
  • Other adverse events (CTCAE, v. 4.0) related to adjuvant paclitaxel or pazopanib hydrochloride/placebo after concurrent treatment (Phase II) [ Time Frame: Up to 4 years ] [ Designated as safety issue: Yes ]
    Only adverse events (AEs) assessed to be definitely, probably, or possibly related to protocol treatment will be considered. The rates of adverse events, discontinuation of treatment, and response will be estimated using a binomial distribution along with their associated 95% confidence intervals and will be compared using Fisher's exact test.
  • Response of the primary site in patients with measurable disease following chemoradiation as per RECIST version 1.1 (Phase II) [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    Estimated using a binomial distribution along with their associated 95% confidence intervals and will be compared using Fisher's exact test.
  • Local-regional control at 6 and 12 months (Phase II) [ Designated as safety issue: No ]
  • Grade 4 (CTCAE, v. 4.0) hemorrhage, grade 4 febrile neutropenia, discontinuation of treatment due to toxicity, or any grade 5 adverse event (Phase II) [ Designated as safety issue: Yes ]
  • Other adverse events (CTCAE, v. 4.0) (Phase II) [ Designated as safety issue: Yes ]
  • Grade 4 (CTCAE, v. 4.0) hemorrhage or any grade 5 adverse event related to adjuvant paclitaxel or pazopanib hydrochloride/placebo after concurrent treatment (Phase II) [ Designated as safety issue: Yes ]
  • Other adverse events (CTCAE, v. 4.0) related to adjuvant paclitaxel or pazopanib hydrochloride/placebo after concurrent treatment (Phase II) [ Designated as safety issue: Yes ]
  • Response as per RECIST of the primary site in patients with measurable disease following chemoradiation (Phase II) [ Designated as safety issue: No ]
Not Provided
Not Provided
 
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

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

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 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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Anaplastic Thyroid Cancer
  • Drug: pazopanib hydrochloride
    Given PO
    Other Names:
    • GW786034B
    • Votrient
  • Radiation: intensity-modulated radiation therapy
    Undergo radiotherapy
    Other Name: IMRT
  • Drug: paclitaxel
    Given IV
    Other Names:
    • Anzatax
    • Asotax
    • TAX
    • Taxol
  • Other: placebo
    Given PO
    Other Name: PLCB
  • Experimental: 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).
    Interventions:
    • Drug: pazopanib hydrochloride
    • Radiation: intensity-modulated radiation therapy
    • Drug: paclitaxel
  • Experimental: 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).
    Interventions:
    • Drug: pazopanib hydrochloride
    • Radiation: intensity-modulated radiation therapy
    • Drug: paclitaxel
    • Other: placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Suspended
121
Not Provided
December 2019   (final data collection date for primary outcome measure)

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
  • 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 (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)
  • 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 QTc prolongation, family history of prolonged QTc, and relevant cardiac disease
  • Evaluation of the patient's medications within 10 days prior to registration with attempt to change any medication that affects cytochrome P450 3A4 (CYP3A4)
  • 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
  • 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 nonmelanomatous skin cancer, differentiated thyroid cancer, or the presence of prostate cancer confined to the prostate with a prostate specific antigen [PSA] =< 1 ng/mL for more than 6 months)
  • 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
    • 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 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)
  • 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 with an arrhythmia are excluded; patients with atrial fibrillation, supraventricular tachycardia, or bradycardia are eligible as these conditions must be well controlled with medication or a pacemaker
  • Patients who require heparin (other than low-molecular weight heparin)
  • Patients with any condition that may impair the ability to swallow or 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 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
  • 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
  • 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
  • Known brain metastases
  • 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 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, nelfinivir, retonavir, 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, CYP2D6, or CYP2C8 should be avoided and, if necessary, administered with caution
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01236547
NCI-2011-02614, NCI-2011-02614, RTOG-0912, CDR0000688092, RTOG 0912, RTOG-0912, U10CA021661
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Eric Sherman Radiation Therapy Oncology Group
National Cancer Institute (NCI)
February 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP