A clinical trial of axitinib plus PF-04856884 or axitinib alone for patientswith metastatic renal cancer who have already been treated with ananti-VEGF agent.

• Conditions: METASTATIC RENAL CELL CARCINOMA; MedDRA version: 14.1Level: SOCClassification code 10029104Term: Neoplasms benign, malignant and unspecified (incl cysts and polyps)System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 14.1Level: LLTClassification code 10038407Term: Renal cell cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2011-002190-33-IT
• Lead Sponsor: PFIZER INC.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-12-20
• Last Update Posted: 7 October 2014

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 165

Inclusion Criteria

Subject eligibility should be reviewed and documented by an appropriately qualified member of the investigator's study team before
subjects are included in the study.
• Evidence of a personally signed and dated informed consent document
indicating that the subject (or a legally acceptable representative) has
been informed of all pertinent aspects of the study.
• Subjects who are willing and able to comply with scheduled visits,
treatment plan, laboratory tests, and other study procedures.
Subjects must meet all of the following inclusion criteria to be eligible
for enrollment into the study:
1. Histologically or cytologically confirmed renal cell cancer (RCC) with a
component of clear cell subtype and evidence of metastasis.
2. Evidence of unidimensionally measurable disease (ie, = 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).
3. Prior therapy:
• Part I: Having received 1-3 prior systemic regimens for treatment of
mRCC.
• Part II: Evidence of disease progression following 1 prior regimen
administered as 1st line therapy for mRCC. The prior regimen must have
contained one of the following:
• VEGFR2 tyrosine kinase inhibitor (TKI) such as (but not limited to)
pazopanib, sunitinib, tivozanib, or sorafenib.
• Other anti VEGF compounds, such as bevacizumab.
4. Adequate bone marrow as defined by the following criteria:
• Platelets =75,000 cells/mm3.
• Absolute neutrophil count (ANC) =1500 cells/mm3.
• Hemoglobin (Hb) =9.0 g/dL.
5. Adequate liver function as defined by the following criteria:
• Bilirubin =1.5 mg/dL.
• AST/ALT =2.5x upper limit of normal (ULN) or =5.0x ULN with
documented liver metastases.
• Partial thromboplastin time (PTT) and Prothrombin time (PT) or
International Normalized Ration (INR) =1.5x ULN.
6. Adequate renal function as defined by:
• Serum creatinine =1.5 mg/dL or calculated or measured creatinine
clearance (CrCl) =50 cc/min using the following formula: Calculated
Creatinine Clearance = (140 - age) x wt (kg) x 0.85 (if female) / 72 x
serum creatinine (mg/dl).
7. Urinary dipstick <2+ protein. If =2+ protein on urine dipstick, then
urine protein to creatinine ratio (UPCR) ratio =0.5 as characterized by
spot urine sample.
8. ECOG performance status 0 or 1.
9. At least two weeks (prior to Day 1) since end of prior systemic
treatment (four weeks for bevacizumab), radiotherapy, or surgical
procedure for RCC with resolution of all treatment-related toxicity
(except alopecia or hypothyroidism) to National Cancer Institute (NCI)
Common Terminology Criteria for Adverse Events (CTCAE) V. 4.0, Grade
=1 or back to baseline.
10. Male or female, age =18 years.
11. Life expectancy =12 weeks.
12. Women of childbearing potential must have a negative serum
pregnancy test within 3 days prior to treatment.
13. Willingness and ability to comply with scheduled visits, treatment
plans, laboratory tests and other study procedures, including in Part II
the completion of the patient-reported outcome (PRO) measures
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 82
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 83

Exclusion Criteria

Subjects presenting with any of the following will not be included in the
study:
1. Subjects who are investigational site staff members or subjects who
are Pfizer employees directly involved in the conduct of the trial.
2. Prior therapy:
• Part I
• Intolerant to prior AG-013736 therapy.
• Prior treatment with compounds which contain the core platform
antibody as PF-04856884. These include CVX-045, CVX-096, and CVX-
241.
• Part II
• Prior AG-013736 therapy.
• More than one systemic first-line regimen for the treatment of mRCC.
• Prior treatment with compounds which contain the core platform
antibody as PF-04856884. These include CVX-045, CVX-096, and CVX-
241.
3. Major surgery <4 weeks or radiation therapy <2 weeks prior to start
of therapy.
4. Clinically significant gastrointestinal abnormalities including any of
the following:
• Inability to take oral medications.
• Requiring intravenous alimentation.
• Malabsorption syndromes.
• Requiring treatment of active ulcer disease in prior six months.
• Prior gastric resection.
• Active gastrointestinal bleeding, related or unrelated to cancer, as
evidenced by either hematemesis, hematochezia, or melena in prior 3
months.
5. Current use or anticipated need for 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) during the course of the study.
6. Current use or anticipated need for drugs that are known CYP3A4 or
CYP1A2 inducers (ie, carbamazapine, dexamethasone, felbamate,
omeprazole, Phenobarbital, phenytoin, primidone, rifabutin, rifampin,
and St. John's wort) during the course of the study.
7. Requirement for therapeutic anticoagulant therapy including daily
aspirin (>325 mg/day) or non steroidal anti inflammatory agents known
to inhibit platelet function. Low dose anti coagulants such as low dose
heparin or 1-2 mg/day of warfarin for prevention of deep vein
thrombosis or maintenance of patency of central venous devices is
permitted.
8. Active seizure disorder or evidence of brain metastases, spinal cord
compression, or carcinomatous meningitis.
• Patients with clinical evidence suggestive of new brain metastases are
excluded if brain metastases have not been ruled out using CT or MRI
imaging.
• Patients with previously diagnosed brain metastases are eligible if
they have completed their radiation therapy to the central nervous
system (CNS) and have recovered from the acute effects of that
treatment prior to enrollment, have discontinued corticosteroid
treatment for these metastases for at least 2 weeks, and are
neurologically stable.
9. History of bleeding diathesis or coagulopathy.
10. NCI CTCAE Grade 3 or greater hemorrhage from any cause <4 weeks
prior to screening.
11. Hemoptysis >½ teaspoon of blood per day within 2 weeks prior to
screening.
12. History of allergic or anaphylactic reaction to any therapeutic or
diagnostic monoclonal antibody or IgG fusion protein.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified