A PIVOTAL PHASE 2 STUDY OF THE ANTI-ANGIOGENESIS AGENT AG-013736IN PATIENTS WITH 131I-REFRACTORY METASTATIC OR UNRESECTABLELOCALLY-ADVANCED PAPILLARY, FOLLICULAR, OR HURTHLE-CELL THYROID CANCER WHO ARE ALSO REFRACTORY TO, OR INTOLERANT OF,OR HAVE CLINICAL CONTRAINDICATION TO, DOXORUBICIN TREATMENT - ND
- Conditions
- Treatment of patients with 131I-refractory metastatic or unresectable locally-advancedpapillary, follicular, or Hurthle-cell thyroid cancer who are also refractory to, or intolerant of,or have clinical contraindication to, doxorubicin treatment.MedDRA version: 9.1Level: LLTClassification code 10055107Term: Thyroid cancer metastatic
- Registration Number
- EUCTR2006-002576-18-IT
- Lead Sponsor
- PFIZER
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 100
1. Histologically documented, 131I-refractory metastatic or unresectable locally-advanced thyroid cancer of papillary, follicular or Hurthle cell histology plus any one of the
following:
- 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 6 months after the last dose of doxorubicin (scans or x-rays must be received and verified by imaging core laboratory before patient can receive treatment);
- Intolerance of doxorubicin therapy, defined as occurrence of life-threatening or grade 4 toxicity attributable to previous therapy with doxorubicin and have at least one measurable target lesion unirradiated by external beam radiation (a maximum of 10 patients will be eligible under this criteria); or
- Doxorubicin therapy is clinically contraindicated, defined as patients who have
received a cumulative doxorubicin dose of >450 mg/m2 during previous therapy.
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 (CT/MRI scans must be received and verified by imaging core laboratory before patient
can receive treatment). Baseline scans must be received by the imaging core laboratory before the patient can receive treatment with AG-013736.
4. Adequate hepatic, and renal function documented within 14 days prior to treatment as documented by:
- AST and ALT
- total bilirubin
- serum creatinine /=60 mL/min
- urinary protein <1+ by urine dipstick. If dipstick is >/=1+ then a 24-hour urine collection can be done and the patient may enter only if urinary protein is <2 g per 24 hours
5. Age >/=18 years.
6. ECOG performance status of 0 or 1 (see Appendix D)
7. No evidence of preexisting uncontrolled hypertension as documented by 2 baseline blood pressure readings taken at least 1 hour apart. The baseline systolic blood pressure readings must be
whose hypertension is controlled by antihypertensive therapies are eligible.
8. Women of childbearing potential must have a negative serum or urine pregnancy test within 3 days prior to treatment.
9. Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures, including completion of MDASI.
10. Written and voluntary informed consent.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-6
1. Central lung lesions involving major blood vessels (arteries or veins). (Central lesions that
maintain the structural integrity of vessels have the potential to bleed if the tumor lesion undergoes necrosis. MRI or CT angiography should be used in any case where there is any question as to whether blood vessels are involved.)
2. Thyroid lymphoma or anaplastic or medullary histology
3. Bleeding from lung (as evidenced by hemoptysis) > 1/2 tsp of bright red blood per day within past 1 week
4. 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.
5. Previous treatment with anti-angiogenesis agents including thalidomide, Sutent (SU-011248), AMG 706, sorafenib, and bevacizumab.
6. 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).
7. 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).
8. Active seizure disorder or evidence of brain metastases, spinal cord compression, or carcinomatous meningitis.
9. A serious uncontrolled medical disorder or active infection that would impair their ability to receive study treatment.
10. 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.
11. 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
12. Major surgical procedure within 4 weeks of treatment.
13. Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol.
14. Patients (male and female) having procreative potential who are not using adequate contraception or practicing abstinence.
15. Women who are pregnant or breast-feeding
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method