Treatment of patients with 131I-refractory metastatic or unresectable locally-advanced papillary, follicular, or Hurthle-cell thyroid cancer who are also refractory to, or intolerant of, or have clinical contraindication to, doxorubicin treatment. MedDRA version: 8.1 Level: LLT Classification code 10055107 Term: Thyroid cancer metastatic
Conditions
Interventions
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: axitinib
CAS Number: 319460-85-0
Current Sponsor code: AG-013736
Concentration unit: mg milligram(s)
Concentration type: equal
Concentratio
Sponsors
Pfizer Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically documented, or 131I-inappropriate metastatic or unresectable locallyadvanced thyroid cancer including papillary, follicular, Hurthle cell, medullary, or anaplastic histologies plus any one of the following: o Failure of 131I to control the disease (documented with radiographic evidence of disease progression defined by RECIST within 12 months prior to enrollment) or 131I is not an appropriate therapy (anaplastic or medullary histology), or lack of iodine uptake by one or more tumors as documented by radioiodine scan. OR o 131I-refractory and failure of doxorubicin (either as a single agent or in combination with other agents) to control the disease, documented with radiographic evidence of disease progression as defined by RECIST criteria and documented with 2 sets of CT/MRI scans (or 2 sets of chest x-rays, bone scans, or x-rays of bone lesion) during doxorubicin therapy or within 12 months after the last dose of doxorubicin 2. If a patient has only locally-advanced cancer without distant metastasis, in addition to satisfying the above inclusion criteria, the disease must also be unresectable (eg, tumor involving vital structure, history of previous surgery in the same area, or concurrent severe medical condition that prevents surgery) AND must be refractory to external beam radiotherapy. 3. At least 1 measurable target lesion, as defined by RECIST. If the only measurable target lesion is located in an externally irradiated field, this lesion may be used as measurable disease only if the lesion diameter has grown by =20 % since completion of the prior external irradiation or if the lesion is a new lesion, assuming all other criteria are met. 4. Adequate hepatic, and renal function documented within 14 days prior to treatment as documented by: - AST and ALT =2.5 x upper limit of normal (ULN), unless there are liver metastases in which case AST and ALT =5.0 x ULN - total bilirubin =1.5 x ULN - serum creatinine =1.5 x ULN or calculated creatinine clearance =60 mL/min - urinary protein =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Thyroid lymphoma 2. Bleeding from lung (as evidenced by hemoptysis) >½ tsp of bright red blood per day within past 1 week 3. Gastrointestinal abnormalities including: - inability to take oral medication - requirement for intravenous alimentation - prior surgical procedures affecting absorption including gastric resection - treatment for active peptic ulcer disease in the past 6 months - active gastrointestinal bleeding, unrelated to cancer, as evidenced by hematemesis, hematochezia or melena in the past 3 months without evidence of resolution documented by endoscopy or colonoscopy. - malabsorption syndromes. 4. Previous treatment with anti-angiogenesis agents including thalidomide, Sutent (SU-011248), AMG 706, sorafenib, and bevacizumab. 5. Current use or anticipated need for treatment with drugs that are known potent CYP3A4 inhibitors (ie, grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, erythromycin, clarithromycin, ergot derivatives, indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, and delavirdine). 6. Current use or anticipated need for treatment with drugs that are known CYP3A4 or CYP1A2 inducers (ie, carbamazepine, dexamethasone, felbamate, omeprazole, phenobarbital, phenytoin, primidone, rifabutin, rifampin, and St. John’s wort). 7. Active seizure disorder or evidence of brain metastases, spinal cord compression, or carcinomatous meningitis. 8. A serious uncontrolled medical disorder or active infection that would impair their ability to receive study treatment. 9. Any of the following within the 12 months prior to study drug administration: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, deep vein thrombosis or pulmonary embolism. 10. History of a malignancy (other than thyroid cancer) except those treated with curative intent for skin cancer (other than melanoma) or in situ breast or cervical cancer or those treated with curative intent for any other cancer with no evidence of disease for 5 years. 11. Major surgical procedure within 4 weeks of treatment. 12. Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol. 13. Patients (male and female) having procreative potential who are not using adequate contraception or practicing abstinence. 14. Women who are pregnant or breast-feeding 15. Requirement of anticoagulant therapy except for low-dose anticoagulants for maintenance of patency of central venous access or prevention of deep vein thrombosis 16. History of hemorrhagic or thrombotic cerebro-vascular event in the past 12 months (DVT)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to determine the objective response rate (ORR) of patients with 131I-refractory metastatic or unresectable locally-advanced papillary, follicular, or Hurthle-cell thyroid cancer who are also refractory to, or intolerant of, or have clinical contraindication to, doxorubicin treatment.;Secondary Objective: Secondary objectives are to: - determine the safety profile of AG-013736 - determine the progression-free survival (PFS) - determine the duration of response (DR) - determine overall survival (OS) - obtain blood samples for population pharmacokinetic analyses - obtain blood samples to conduct exploratory studies monitoring circulating endothelial cells as markers of drug response and/or disease - obtain blood samples for UGT1A1 mutation correlation with safety and efficacy - explore patient reported outcomes (PROs) of symptom severity and interference in this study population;Primary end point(s): Primary end point: Objective Response Rate (ORR), defined as the proportion of patients with confirmed complete response (CR) or confirmed partial response (PR) according to the Response Evaluation Criteria in Solid Tumors (RECIST), relative to the total population of patients who received at least 1 dose of study medication. Secondary end points: Progression Free Survival (PFS) defined as the time from start of study treatment to first documentation of objective tumor progression or to death due to any cause, whichever comes first. Duration of Respons (DR) defined as the time from the first documentation of objective tumor response (unconfirmed complete response or unconfirmed partial response, whichever occurs first) that is subsequently confirmed to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first. Overall survival (OS) defined as the time from the start of study treatment to date of death due to any cause. | — |
Countries
Czech Republic, Italy, Spain
Outcome results
None listed