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A Phase I/ II Trial of Pazopanib Alternating With Bevacizumab in Treatment-Naive Metastatic Clear Cell Renal Cell Carcinoma Patients

Phase 1/Phase 2
18 Years
Open (Enrolling)
Clear Cell Renal Cell Carcinoma, Stage IV Renal Cell Cancer

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Trial Information

A Phase I/ II Trial of Pazopanib Alternating With Bevacizumab in Treatment-Naive Metastatic Clear Cell Renal Cell Carcinoma Patients


I. To determine the safe phase II dose of this novel regimen. (Phase I) II. To determine the
median progression free survival (PFS) from this novel regimen. (Phase II)


I. To evaluate the safety and toxicity of the proposed regimen. (Phase I) II. To evaluate
the response rate. (Phase I) III. To evaluate the pharmacokinetics of pazopanib (pazopanib
hydrochloride). (Phase I) IV. To evaluate the vascular endothelial growth factor (VEGF)
levels and myeloid derived suppressor cell (MDSC) levels at various time points and
correlate with response. (Phase I) V. To evaluate the safety and toxicity of this new
regimen. (Phase II) VI. To evaluate the VEGF levels, interleukin (IL)-8 levels and MDSC
levels at various time points and correlate with outcome. (Phase II) VII. To evaluate the
PFS rate at 12 months. (Phase II) VIII. To evaluate overall survival. (Phase II)

OUTLINE: This is a dose-escalation study.

Patients receive pazopanib hydrochloride orally (PO) on days 1-28 and bevacizumab
intravenously (IV) over 30-90 minutes on days 36 and 50. Courses repeat every 70 days in the
absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days.

Inclusion Criteria:

- Biopsy/pathology-proven clear cell renal cell carcinoma (CCRCC) with metastases

- Have an Eastern Cooperative Oncology Group (ECOG) performance status =< 1

- Hemoglobin >= 10 gm/dL

- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L

- Platelets >= 100 x 10^9/L

- Total bilirubin =< upper limit of normal (ULN)

- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< ULN

- International normalization ratio ([NR) and activated partial thromboplastin time
(aPTT) < 1.2 x ULN

- Serum creatinine < 1.5 mg/dL or if serum creatinine > 1.5 mg/dL then calculate
creatinine clearance (CrCL) > 30 mL/min

- Urine protein to creatinine ratio =< 1 (if urine protein creatinine ratio is > 1,
then a 24-hour urine total protein must be assessed; subjects will be ineligible if
the 24-hour urine protein is found to be > 1 gm)

- Normal cardiac ejection fraction (> 50%) by multi gated acquisition scan (MUGA) or

- Have measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
criteria present

- Ability to swallow and retain oral medication

- Subjects of child-bearing potential must agree to use adequate contraceptive methods
(e.g., hormonal or barrier method of birth control; abstinence) prior to study entry
and for the duration of study participation; should a woman become pregnant or
suspect she is pregnant while she or her partner is participating in this study, she
should inform her treating physician immediately

- Subject or legal representative must understand the investigational nature of this
study and sign an Independent Ethics Committee/Institutional Review Board approved
written informed consent form prior to receiving any study related procedure

Exclusion Criteria:

- Subjects with known brain metastases should be excluded from this clinical trial

- Prior VEGF targeted therapies for renal cell carcinoma (RCC) including adjuvant or
neoadjuvant treatments

- Subjects diagnosed with another cancer in the past 3 years; excluding basal cell
carcinoma or squamous cell carcinoma, of skin which were completely cured by

- Concurrent use of another anti-cancer drug including an investigational anti-cancer

- Major surgery within 28 days prior to treatment or major surgery planned during the
next 6 months

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic or psychiatric illness/social situations that would limit
compliance with study requirements

- History of any of the following cardio-vascular condition:

- Myocardial infarction (MI)

- Unstable angina

- Coronary artery bypass grafting (CABG)

- Coronary angioplasty or stenting

- Symptomatic peripheral arterial disease (PAD)

- History of symptomatic chronic congestive heart failure (CHF)

- History of cerebrovascular accidents including transient ischemic attacks (TIA)

- Corrected QT interval (QTc) > 480 msec

- Uncontrolled hypertension (systolic blood pressure [BP] > 150 mm Hg or diastolic
BP of > 90 mm Hg); if the screening BP is elevated, adjustments in
anti-hypertensives are permitted and a re-screening will be permitted for BP
assessment with three consecutive values obtained 2 minutes apart; the 3 values
have to be below 150/90 mm Hg for eligibility and can only be obtained after 2
days of the last change in anti-hypertensive medication; use of clonidine is not
permissible for adjusting the BP during this period

- History of deep vein thrombosis (DVT) or pulmonary embolism (PE) in the past 6 months

- Subjects should not have packed red blood cells (PRBC) or platelet transfusion within
14 days of the screening

- Evidence of active bleeding or bleeding disorder

- Subjects currently on anti-coagulation therapy are not eligible

- Unable to discontinue the use of prohibited medications

- Pregnant or nursing female subjects

- Unwilling or unable to follow protocol requirements

- Any condition which in the investigator's opinion deems the subject an unsuitable
candidate to receive study drug

- Received an investigational agent within 30 days prior to enrollment

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Optimal phase II dose defined as the largest dose level at which less than 2 out of the 6 patients experienced dose-limiting toxicity (DLT) assessed based on Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (Phase I)

Outcome Time Frame:

Up to 140 days

Safety Issue:


Principal Investigator

Saby George

Investigator Role:

Principal Investigator

Investigator Affiliation:

Roswell Park Cancer Institute


United States: Food and Drug Administration

Study ID:

I 191711



Start Date:

October 2012

Completion Date:

Related Keywords:

  • Clear Cell Renal Cell Carcinoma
  • Stage IV Renal Cell Cancer
  • Carcinoma
  • Carcinoma, Renal Cell



Roswell Park Cancer InstituteBuffalo, New York  14263