Trial record 6 of 34 for:    "Thyroid cancer anaplastic"

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by National Cancer Institute (NCI)
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01236547
First received: November 5, 2010
Last updated: July 22, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Anaplastic Thyroid Cancer
Drug: paclitaxel
Drug: pazopanib hydrochloride
Other: placebo
Radiation: intensity-modulated radiation therapy
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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 (Phase II) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    Estimated using the Kaplan-Meier method.


Secondary Outcome Measures:
  • 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 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.


Estimated Enrollment: 121
Study Start Date: October 2010
Estimated Primary Completion Date: October 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (paclitaxel, pazopanib hydrochloride, IMRT)
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).
Drug: paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol
Drug: pazopanib hydrochloride
Given PO
Other Names:
  • GW786034B
  • Votrient
Radiation: intensity-modulated radiation therapy
Undergo IMRT
Other Name: IMRT
Active Comparator: Arm II (paclitaxel, placebo, IMRT)
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).
Drug: paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • TAX
  • Taxol
Other: placebo
Given PO
Other Name: PLCB
Radiation: intensity-modulated radiation therapy
Undergo IMRT
Other Name: IMRT

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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; Note: 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 corrected QT (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
  • 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 II 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 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 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, 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, 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01236547

  Show 37 Study Locations
Sponsors and Collaborators
Investigators
Principal Investigator: Eric Sherman NRG Oncology
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT01236547     History of Changes
Other Study ID Numbers: NCI-2011-02614, NCI-2011-02614, CDR0000688092, RTOG 0912, RTOG-0912, U10CA180868, U10CA021661
Study First Received: November 5, 2010
Last Updated: July 22, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Thyroid Neoplasms
Thyroid Diseases
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Head and Neck Neoplasms
Endocrine System Diseases
Paclitaxel
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 24, 2014