AXITINIB (AG 013736) AS SECOND LINE THERAPY FOR METASTATIC RENAL CELL CANCER: AXIS TRIA

Phase 1

Conditions: Renal cell carcinoma
MedDRA version: 14.1 Level: PT Classification code 10050513 Term: Metastatic renal cell carcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2008-001451-21-GB

Lead Sponsor: Pfizer Inc.,235 East 42nd Street,New York,NY 10017

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: Not specified

Target Recruitment: 723

Inclusion Criteria

Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the trial:
1. Histologically or cytologically confirmed renal cell cancer with a component of clear cell subtype, with metastasis.
2. Evidence of unidimensionally measurable disease (ie, =1 malignant tumor mass that can be accurately measured in at least 1 dimension = 20 mm with conventional computerized tomography [CT] scan or Magnetic Resonance Imaging [MRI], or =10 mm with spiral CT scan using a 5 mm or smaller contiguous reconstruction algorithm). Bone lesions, ascites, peritoneal carcinomatosis or miliary lesions, pleural or pericardial effusions, lymphangitis of the skin or lung, cystic lesions, or irradiated lesions are not considered measurable.
3. Must have progressive disease per RECIST (version 1.0) after one prior systemic
first-line regimen for metastatic renal cell cancer. The prior regimen must have contained one or more of the following: sunitinib, bevacizumab + IFN a, temsirolimus, or cytokine(s).
4. Adequate organ function as defined by the following criteria:
• absolute neutrophil count (ANC) =1500 cells/mm3;
• platelets =75,000 cells/mm3.
• Hemoglobin =9.0 g/dL.
• 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 <2+ by urine dipstick. If dipstick is =2+ 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. Male or female, age =18 years. (20 years in Japan)
6. ECOG performance status of 0 or 1.
7. Life expectancy of =12 weeks.
8. At least 2 weeks since the end of prior systemic treatment (4 weeks for bevacizumab + IFN a), radiotherapy, or surgical procedure with resolution of all treatment-related toxicity to NCI CTCAE Version 3.0 grade =1 or back to baseline except for alopecia or hypothyroidism.
9. 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 =140 mm Hg, and the baseline diastolic blood pressure readings must be =90 mm Hg. Patients whose hypertension is controlled by antihypertensive therapies are eligible.
10. Women of childbearing potential must have a negative serum or urine pregnancy test within 3 days prior to treatment.
11. Signed and dated informed consent document indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the trial prior to enrollment.
12. Willingness and ability to comply with scheduled visits, treatment plans (including
willingness to take either AG-013736 or sorafenib according to randomization),
laboratory tests, and other study procedures, including completion of patient-reported outcome measures (FKSI and EQ-5D questionnaires).
Are the trial subjects under 18? no
Number of subjects for this age range:

Exclusion Criteria

Subjects presenting with any of the following will not be included in the trial:
1. Prior treatment of mRCC with more than one systemic first-line regimen.
2. Patients treated with any neoadjuvant or adjuvant systemic therapy.
3. Major surgery <4 weeks or radiation therapy <2 weeks of starting the study treatment.
Prior palliative radiotherapy to metastatic lesion(s) is permitted, provided there is at least one measurable lesion that has not been irradiated.
4. Gastrointestinal abnormalities including:
• inability to take oral medication;
• requirement for intravenous alimentation;
• prior surgical procedures affecting absorption including total 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. Current use or anticipated need for treatment with drugs that are known potent CYP3A4 inhibitors (ie, grapefruit juice, verapamil, ketoconazole, miconazole, itraconazole, erythromycin, telithromycin, clarithromycin, indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, atazanavir, amprenavir, fosamprenavir 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, amobarbital, nevirapine, primidone, rifabutin, rifampin, and St.John’s wort).
7. Requirement of anticoagulant therapy with oral vitamin K antagonists. Low-dose
anticoagulants for maintenance of patency of central venous access devise or prevention of deep venous thrombosis is allowed. Therapeutic use of low molecular weight heparin is allowed.
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, uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack and 6 months for deep vein thrombosis or pulmonary embolism.
11. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness.
12. History of a malignancy (other than renal cell cancer) except those treated with curative intent for skin cancer (other than melanoma), in situ breast or in situ cervical cancer, or those treated with curative intent for any other cancer with no evidence of disease for 2 years.
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. Female patients who are pregnant or lactating, or men and women of reproductive potential not willing or not

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

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