RANDOMIZED, DOUBLE-BLIND PHASE 2 STUDY OF AXITINIB (AG-013736) WITH OR WITHOUT DOSE TITRATION IN PATIENTS WITH METASTATIC RENAL CELL CARCINOMA

• Register: EUCTR
• Last refreshed on: 10 October 2016
• Main ID: EUCTR2008-007786-23-CZ
• Date of registration: 02/03/2009
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc 235 East 42nd Street, New York, NY10017
• Public title: RANDOMIZED, DOUBLE-BLIND PHASE 2 STUDY OF AXITINIB (AG-013736) WITH OR WITHOUT DOSE TITRATION IN PATIENTS WITH METASTATIC RENAL CELL CARCINOMA
• Scientific title: RANDOMIZED, DOUBLE-BLIND PHASE 2 STUDY OF AXITINIB (AG-013736) WITH OR WITHOUT DOSE TITRATION IN PATIENTS WITH METASTATIC RENAL CELL CARCINOMA
• Date of first enrolment: 21/09/2009
• Target sample size: 200
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-007786-23
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Czech Republic, Germany, Spain

Key inclusion & exclusion criteria

Inclusion criteria:
1. Histologically confirmed mRCC with a component of clear cell histology.
2. No prior systemic therapy for mRCC (including no prior adjuvant or neoadjuvant therapy)
3. If patient has had prior radiation therapy or surgery, then at least 1 week has elapsed since the end of prior radiotherapy; at least 4 weeks since major surgery. All prior treatment-related toxicity must be resolved to NCI CTCAE Version 3.0 grade 4. Presence of measurable disease (i.e., >/=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 biliary lesions, pleural or pericardial
effusions, lymphangitic spread to the skin or lung, cystic lesions, or irradiated lesions are not considered measurable. Prior palliative radiotherapy to metastatic lesion(s) is permitted, provided there is at least one measurable lesion that has not been irradiated
5. No uncontrolled hypertension as documented by 2 baseline blood pressure readings taken at least 1 hour apart: the baseline systolic blood pressure readings must be 6. 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/d.
• AST and ALT • Total bilirubin • Serum creatinine /= 60 mL/min;
• Urinary protein <2+ by urine dipstick. If dipstick is >/= 2+, then a 24-hour urine
protein should be done and results must show protein <2 g per 24 hours.
7. Male or female, age >/=18 years.
8. ECOG performance status of 0 or 1.
9. Life expectancy of >/=12 weeks.
10. Female patients or their partners must be surgically sterile or be postmenopausal, or must agree to use effective contraception while receiving study treatment and for at least 3 months thereafter (or up to 6 months, if required by local regulations). All female patients with reproductive potential must have a negative pregnancy test (serum/urine) within the 72 hours prior to starting treatment. Male patients or their partners must be surgically sterile or must agree to use effective contraception while receiving study treatment and for at least 3 months thereafter (or up to 6 months, if
required by local regulations). The definition of effective contraception should be in agreement with local regulation and based on the judgment of the principal investigator or a designated associate. Breastfeeding women are not eligible for the
study.
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, laboratory tests, and other study procedures.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Concurrent use of more than 2 anti-hypertensive medications.
2. Prior use of axitinib (AG-013736).
3. Gastrointestinal abnormalities such as 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.
4. Current use or anticipated need for treatment with drugs that are known potent CYP3A4 inhibitors (i.e., grapefruit juice, verapamil, ketoconazole, miconazole,
itraconazole, erythromycin, telithromycin, clarithromycin, indinavir, saquinavir, ritonavir, nelfinavir, lopinavir, atazanavir, amprenavir, fosamprenavir and delavirdine).
5. Current use or anticipated need for treatment with drugs that are known CYP3A4 or CYP1A2 inducers (i.e., carbamazepine, dexamethasone, felbamate, omeprazole, phenobarbital, phenytoin, amobarbital, nevirapine, primidone, rifabutin, rifampin, and St. John’s wort).
6. Ongoing or recent (within 10 days prior treatment start) need for full therapeutic dose of oral or parenteral anticoagulant or chronic daily treatment with aspirin (>325 mg/day) or clopidogrel (> 75mg/day)
7. Seizure disorder or evidence of brain metastases, spinal cord compression, or carcinomatous meningitis.
8. 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 and 6 months for deep vein thrombosis or pulmonary embolism
9. Active bacterial, fungal or viral infection; known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness.
10. History of a malignancy (other than renal cell cancer) except those treated with curative intent for non-melanoma skin cancer, 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.
11. Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol.
12. Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in
the judgment of the investigator would make the patient inappropriate for entry into this study.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Metastatic RCC
MedDRA version: 9.1 Level: LLT Classification code 10050513 Term: Metastatic renal cell carcinoma

Intervention(s)

Product Name: Axintinib
Product Code: AG-013736
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: axitinib
CAS Number: 319460-85-0
Current Sponsor code: AG-013736
Other descriptive name: Benzamide, N-methyl-2-[[3-[(1E)-2-(2-pyridinyl)ethenyl]-1H-indazol-6-yl]thio]-
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: Axintinib
Product Code: AG-013736
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: axitinib
CAS Number: 319460-85-0
Current Sponsor code: AG-013736
Other descriptive name: Benzamide, N-methyl-2-[[3-[(1E)-2-(2-pyridinyl)ethenyl]-1H-indazol-6-yl]thio]-
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: To assess the safety profile, other efficacy parameters, pharmacokinetics, biomarker and/or gene expression profiling correlations with clinical outcome and/or BP measurements in patients receiving axitinib with or without dose titration (Arms A and B). Although the main study comparison is between Arms A and B, additional information such as those related to safety and biomarker/gene expression profiling correlations with clinical outcome will also be assessed in the non-randomized group, Arm C.

Primary end point(s): ORR (Arms A vs B)

Main Objective: To compare the objective response rate (ORR) in patients receiving axitinib with or without dose titration (Arms A and B)

Secondary ID(s)

A4061046

2008-007786-23-ES