Iodine I 131 and Pazopanib Hydrochloride in Treating Patients With Recurrent and/or Metastatic Thyroid Cancer Previously Treated With Iodine I 131 That Cannot Be Removed By Surgery

NCT01413113 | Completed Phase 1

• 3 other identifiers: 7529NCI-2011-01139P30CA015704
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial is studying the side effects and best dose of iodine I 131 when given together with pazopanib hydrochloride in treating patients with recurrent and/or metastatic thyroid cancer previously treated with iodine I 131 that cannot be removed by surgery. Radioactive drugs, such as iodine I 131, may carry radiation directly to cancer cells and not harm normal cells. Pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving iodine I 131 together with pazopanib hydrochloride may be an effective treatment for thyroid cancer.

Conditions

Recurrent Thyroid Cancer; Stage IVA Follicular Thyroid Cancer; Stage IVA Papillary Thyroid Cancer; Stage IVB Follicular Thyroid Cancer; Stage IVB Papillary Thyroid Cancer; Stage IVC Follicular Thyroid Cancer; Stage IVC Papillary Thyroid Cancer

Outcome Measures

Primary Outcomes (1)

• Toxicity and the occurrence of dose limiting toxicity (DLT) when pazopanib is given in conjunction with radioiodine to establish the MTD and RP2D in combination

  Assessment of adverse events will include type, incidence, severity (graded by the National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE\], Version 4.03), timing, seriousness, and relatedness; and laboratory abnormalities. Descriptive statistics will be calculated for all variables and responses; continuous data will be expressed as their mean +/- standard deviation, median and range, and categorical data will be listed by frequency of occurrence and proportion of total (with 95% confidence intervals) for all enrolled patients and by dose cohort.

  8 weeks post radioactive iodine administration

Secondary Outcomes (2)

• Tumor response

  At week 14

• TTP

  At week 14

Other Outcomes (1)

• Increased radioiodine uptake, retention and correlative effects of pazopanib on tumor blood flow and response in WDTC (assessed by dynamic FDG-PET)

  At 14 week

Study Arms (1)

Treatment (enzyme inhibitor and radioactive drug therapy)

EXPERIMENTAL

Patients receive iodine I 131 IM QD 5 days a week in weeks 5-6. Patients also receive pazopanib hydrochloride PO QD beginning in week 1 and continuing for 8 weeks post-radioactive iodine therapy.

Drug: pazopanib hydrochloride; Radiation: iodine I 131

Interventions

pazopanib hydrochloride DRUG

Given PO

Also known as: GW786034B, Votrient

Treatment (enzyme inhibitor and radioactive drug therapy)

iodine I 131 RADIATION

Given IM

Also known as: I 131, Iodotope, Iodotrope

Treatment (enzyme inhibitor and radioactive drug therapy)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must provide written informed consent prior to performance of study-specific procedures or assessments, and must be willing to comply with treatment and follow up; procedures conducted as part of the subject's routine clinical management (e.g., blood count, imaging study) and obtained prior to signing of informed consent may be utilized for screening or baseline purposes provided these procedures are conducted as specified in the protocol
• Histologically confirmed diagnosis of well-differentiated thyroid carcinoma (WDTC), including papillary and follicular subtypes, and documented recurrent and/or metastatic disease; patients must have unresectable disease: patients must not be amenable to surgery but prior thyroidectomy is allowed
• Patient must have demonstrated evidence of disease progression by RECIST criteria using site assessment of computed tomography (CT)/magnetic resonance imaging (MRI) scans within 12 months (+1 month to allow for variances in patient scanning intervals) prior to study entry or by \> 50% increase in suppressed thyroglobulin levels during this time period
• Patients with WDTC must be relatively 131I refractory/resistant as defined by at least one of the following:
• One or more measurable lesions with low or absent 131I uptake on the most recent pre-study radioiodine scans, based on a visual review of scans or RAI scan reports
• One or more measurable lesions with disease progression by RECIST within 12 months (+ 1 month to allow for variances in patient scanning intervals) of 131I therapy despite 131I uptake on RAI scan, based on site assessment of CT/MRI scans or by \> 50% increase in suppressed thyroglobulin levels during this time period
• Evidence of at least one site of known disease with preserved 131I uptake above background levels on a diagnostic post-therapy 131I scan prior to study entry
• Patients with WDTC must be receiving thyroxine suppression therapy and thyroid-stimulating hormone (TSH) should not be elevated (TSH should be =\< 5.50 mcu/mL)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Absolute neutrophil count (ANC) \>= 1.5 X 10\^9/L
• Hemoglobin \>= 9 g/dL (5.6 mmol/L)
• Platelets \>= 90 X 10\^9/L
• International normalized ratio (INR) =\< 1.2 X upper limit of normal (ULN); subjects receiving anticoagulant therapy are eligible if their INR is stable and within the recommended range for the desired level of anticoagulation
• Activated partial thromboplastin time (aPTT) =\<1.2 X ULN
• Total bilirubin =\< 1.5 X ULN

You may not qualify if:

• Patients with medullary thyroid cancer, thyroid lymphoma or anaplastic thyroid cancer are excluded
• Resolution of all acute toxic effects of prior systemic therapy (including iodine therapy or systemic therapy), radiotherapy or surgical procedure to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 grade =\< 1
• Patients with cumulative iodine I 131 exposure in excess of 1000 mCi
• Second primary malignancy that is of clinical significance, clinical detectable and/or progressing at the time of consideration for study enrollment
• History or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS metastases, are asymptomatic, and have had no requirement for steroids for 28 days prior to first dose of study drug; screening with CNS imaging studies (CT or MRI) is required only if clinically indicated or if the subject has a history of CNS metastases; clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to:
• Active peptic ulcer disease
• Known intraluminal metastatic lesion/s with risk of bleeding
• Inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease), or other gastrointestinal conditions with increased risk of perforation
• History of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment
• Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to:
• Malabsorption syndrome
• Major resection of the stomach or small bowel
• Presence of uncontrolled infection
• Corrected QT interval (QTc) \> 480 msecs using Bazett's formula
• History of any one or more of the following cardiovascular conditions within the past 6 months:

Sponsors & Collaborators

• University of Washington: lead
• GlaxoSmithKline: collaborator
• National Cancer Institute (NCI): collaborator
• National Comprehensive Cancer Network: collaborator

Study Sites (1)

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

Related Publications (1)

• Chow LQ, Santana-Davila R, Pantel A, Roth M, Anderson LN, Failor A, Doot R, Mankoff D. A phase I study of pazopanib in combination with escalating doses of 131I in patients with well-differentiated thyroid carcinoma borderline refractory to radioiodine. PLoS One. 2017 Jun 29;12(6):e0178325. doi: 10.1371/journal.pone.0178325. eCollection 2017.

  PMID: 28662033 DERIVED

MeSH Terms

Conditions

Thyroid Neoplasms; Adenocarcinoma, Follicular; Thyroid Cancer, Papillary

Interventions

pazopanib; Iodine-131

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Endocrine System Diseases; Thyroid Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Adenocarcinoma, Papillary

Study Officials

• Laura Chow

  Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2011
• First Posted: August 10, 2011
• Study Start: December 1, 2011
• Primary Completion: November 1, 2013
• Study Completion: October 1, 2015
• Last Updated: November 5, 2015

Record last verified: 2015-11

Locations

US (1)