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

Uncategorized

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

Condition: Clear Cell Renal Cell Carcinoma, Stage IV Renal Cell Cancer

Intervention:

  • Biological: Bevacizumab
  • Other: Laboratory Biomarker Analysis
  • Drug: Pazopanib Hydrochloride
  • Other: Pharmacological Study

Purpose: This phase I/II trial studies the side effects and best dose of pazopanib hydrochloride and bevacizumab and to see how well they work in treating patients with previously untreated kidney cancer that has spread to other places in the body (metastatic). Pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Pazopanib hydrochloride may also stop the growth of tumor cells by blocking blood flow to the tumor. Monoclonal antibodies, such as bevacizumab, can prevent tumor growth by blocking the ability of tumor cells to grow and spread. Giving pazopanib hydrochloride together with bevacizumab may kill more tumor cells.

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT01684397

Sponsor: Roswell Park Cancer Institute

Primary Outcome Measures:

  • Measure: Median PFS (Phase II)
  • Time Frame: Up to 30 days post-treatment
  • Safety Issue:
  • 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, graded according to Common Terminology Criteria for Adverse Events version 4.0 (Phase I)
  • Time Frame: Up to 140 days
  • Safety Issue:

Secondary Outcome Measures:

  • Measure: Incidence of grade 3 or higher toxicities, graded according to CTCAE version 4.0
  • Time Frame: Up to 30 days post-treatment
  • Safety Issue:
  • Measure: Overall survival (Phase II)
  • Time Frame: From the date of study enrollment to the date of death from any cause, assessed up to 30 days post-treatment
  • Safety Issue:
  • Measure: PFS rate at 12 months (Phase II)
  • Time Frame: At 12 months
  • Safety Issue:
  • Measure: Response rate according to RECIST 1.1 (Phase I)
  • Time Frame: Up to 30 days post-treatment
  • Safety Issue:

Estimated Enrollment: 35

Study Start Date: October 5, 2012

Phase: Phase 1/Phase 2

Eligibility:

  • Age: minimum 18 Years maximum N/A
  • Gender: All

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 (INR) 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 echocardiogram
  • 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; in phase 1 only, one prior therapy with high dose IL-2 or anti-programmed cell death (PD)-1 compound alone or in combination with cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) targeting drug is allowed on the trial
  • 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 resection
  • Concurrent use of another anti-cancer drug including an investigational anti-cancer agent
  • 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

Locations:

  • Karamanos Cancer Institute
  • Detroit Michigan 482018 United States
  • Roswell Park Cancer Institute
  • Buffalo New York 14263 United States
  • University of Pittsburgh Cancer Institute (UPCI)
  • Pittsburgh Pennsylvania 15232 United States
  • Medical College of Wisconsin
  • Milwaukee Wisconsin 53226 United States

View trial on ClinicalTrials.gov

X