Trial record 1 of 1 for:    NCT01684397
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Pazopanib Hydrochloride and Bevacizumab in Treating Patients With Previously Untreated Metastatic Kidney Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Roswell Park Cancer Institute
Sponsor:
Collaborators:
GlaxoSmithKline
Information provided by (Responsible Party):
Roswell Park Cancer Institute
ClinicalTrials.gov Identifier:
NCT01684397
First received: August 24, 2012
Last updated: August 4, 2014
Last verified: August 2014
  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, metastatic kidney cancer. 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 block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving pazopanib hydrochloride together with bevacizumab may kill more tumor cells


Condition Intervention Phase
Clear Cell Renal Cell Carcinoma
Stage IV Renal Cell Cancer
Drug: pazopanib hydrochloride
Biological: bevacizumab
Other: pharmacological study
Other: laboratory biomarker analysis
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/ II Trial of Pazopanib Alternating With Bevacizumab in Treatment-Naive Metastatic Clear Cell Renal Cell Carcinoma Patients

Resource links provided by NLM:


Further study details as provided by Roswell Park Cancer Institute:

Primary Outcome Measures:
  • 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) [ Time Frame: Up to 140 days ] [ Designated as safety issue: Yes ]
  • Median PFS (Phase II) [ Time Frame: Up to 30 days post-treatment ] [ Designated as safety issue: No ]
    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:
  • Incidence of grade 3 or higher toxicities accessed based on CTCAE version 4.0 (Phase I) [ Time Frame: Up to 30 days post-treatment ] [ Designated as safety issue: Yes ]
  • Response rate according to RECIST 1.1 (Phase I) [ Time Frame: Up to 30 days post-treatment ] [ Designated as safety issue: No ]
  • Pharmacokinetics of pazopanib (Phase I) [ Time Frame: Course 1 on day 1 at pre-dose, 2 hours, and 4 hours post-dose; day 15 at pre-dose and 2 hours post-dose; and day 29 ] [ Designated as safety issue: No ]
  • VEGF levels, IL-8 levels and MDSC levels (Phase I) [ Time Frame: Up to 30 days post-treatment ] [ Designated as safety issue: No ]
  • Incidence of grade 3 or higher toxicities accessed based on CTCAE version 4.0 (Phase II) [ Time Frame: Up to 30 days post-treatment ] [ Designated as safety issue: Yes ]
    Categorical variables will be summarized in contingency tables, with associations of interest assessed using Fisherâs exact test.

  • VEGF levels, IL-8 levels and MDSC levels (Phase II) [ Time Frame: Up to 30 days post-treatment ] [ Designated as safety issue: No ]
    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.

  • PFS rate at 12 months (Phase II) [ Time Frame: At 12 months ] [ Designated as safety issue: No ]
    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.

  • 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 ] [ Designated as safety issue: No ]
    Will be obtained using Kaplan-Meier and Proportional Hazards methods.


Estimated Enrollment: 66
Study Start Date: October 2012
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (pazopanib hydrochloride and bevacizumab)
Patients 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.
Drug: pazopanib hydrochloride
Given PO
Other Names:
  • GW786034B
  • Votrient
Biological: bevacizumab
Given IV
Other Names:
  • anti-VEGF humanized monoclonal antibody
  • anti-VEGF monoclonal antibody
  • Avastin
  • rhuMAb VEGF
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Other: laboratory biomarker analysis
Correlative studies

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 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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 ([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 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
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01684397

Locations
United States, New York
Roswell Park Cancer Institute Recruiting
Buffalo, New York, United States, 14263
Contact: Roswell Park    877-275-7724    ASKRPCI@roswellpark.org   
Principal Investigator: Saby George         
United States, Pennsylvania
University of Pittsburg Medical Center, Hillman Cancer Center Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Rahul A Parikh, MD, PhD    412-692-4724    parikhr@upmc.edu   
Contact: Bethany Flaherty    412-623-8962    schnelbachb@upmc.edu   
Principal Investigator: Rahul A Parikh, MD, PhD         
Sponsors and Collaborators
Roswell Park Cancer Institute
GlaxoSmithKline
Investigators
Principal Investigator: Saby George Roswell Park Cancer Institute
  More Information

No publications provided

Responsible Party: Roswell Park Cancer Institute
ClinicalTrials.gov Identifier: NCT01684397     History of Changes
Other Study ID Numbers: I 191711, NCI-2012-01247
Study First Received: August 24, 2012
Last Updated: August 4, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Carcinoma, Renal Cell
Carcinoma
Adenocarcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Bevacizumab
Antibodies
Antibodies, Monoclonal
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Immunologic Factors

ClinicalTrials.gov processed this record on October 01, 2014