Clinical Trials /

Pazopanib Hydrochloride and Bevacizumab in Treating Patients With Previously Untreated Metastatic Kidney Cancer

NCT01684397

Description:

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.

Related Conditions:
  • Clear Cell Renal Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Pazopanib Hydrochloride and Bevacizumab in Treating Patients With Previously Untreated Metastatic Kidney Cancer
  • Official Title: A Phase I/II Trial of Pazopanib Alternating With Bevacizumab in Treatment-Naive Metastatic Clear Cell Renal Cell Carcinoma Patients

Clinical Trial IDs

  • ORG STUDY ID: I 191711
  • SECONDARY ID: NCI-2012-01247
  • SECONDARY ID: 13-069
  • SECONDARY ID: I 191711
  • SECONDARY ID: P30CA016056
  • NCT ID: NCT01684397

Conditions

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

Interventions

DrugSynonymsArms
BevacizumabAnti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF rhuMAb, Avastin, Bevacizumab Biosimilar BEVZ92, Bevacizumab Biosimilar BI 695502, Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer, Recombinant Humanized Anti-VEGF Monoclonal Antibody, rhuMab-VEGFTreatment (pazopanib hydrochloride and bevacizumab)
Pazopanib HydrochlorideGW786034B, VotrientTreatment (pazopanib hydrochloride and bevacizumab)

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.

Detailed Description

      PRIMARY OBJECTIVES:

      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)

      SECONDARY OBJECTIVES:

      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 phase I, dose-escalation study followed by a phase II 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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (pazopanib hydrochloride and bevacizumab)ExperimentalPatients receive pazopanib hydrochloride PO on days 1-28 and bevacizumab IV over 30-90 minutes on days 36 and 50. Courses repeat every 70 days in the absence of disease progression or unacceptable toxicity.
  • Bevacizumab
  • Pazopanib Hydrochloride

Eligibility Criteria

        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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Median PFS (Phase II)
Time Frame:Up to 30 days post-treatment
Safety Issue:
Description:Distributions of continuous variables will be summarized with commonly used statistics (mean, standard deviation, median, etc.), with sub-group associations tested using the Wilcoxon Rank Sum test.

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:
Description:Categorical variables will be summarized in contingency tables, with associations of interest assessed using Fisher's exact test. The frequency of toxicities will be tabulated by grade across all dose levels and courses.
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:
Description:Will be obtained using Kaplan-Meier and Proportional Hazards methods.
Measure:PFS rate at 12 months (Phase II)
Time Frame:At 12 months
Safety Issue:
Description:Distributions of continuous variables will be summarized with commonly used statistics (mean, standard deviation, median, etc.), with sub-group associations tested using the Wilcoxon Rank Sum test.
Measure:Response rate according to RECIST 1.1 (Phase I)
Time Frame:Up to 30 days post-treatment
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Roswell Park Cancer Institute

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