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

NCT01684397 | Active Not Recruiting Phase 1 DMC

• 3 other identifiers: I 191711NCI-2012-0124713-069
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Clear Cell Renal Cell Carcinoma; Stage IV Renal Cell Cancer

Outcome Measures

Primary Outcomes (2)

• Median PFS (Phase II)

  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.

  Up to 30 days post-treatment

• 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)

  The frequency of toxicities will be tabulated for the dose estimated to be the maximum-tolerated dose.

  Up to 140 days

Secondary Outcomes (4)

• Incidence of grade 3 or higher toxicities, graded according to CTCAE version 4.0

  Up to 30 days post-treatment

• Overall survival (Phase II)

  From the date of study enrollment to the date of death from any cause, assessed up to 30 days post-treatment

• PFS rate at 12 months (Phase II)

  At 12 months

• Response rate according to RECIST 1.1 (Phase I)

  Up to 30 days post-treatment

Other Outcomes (4)

• IL-8 levels

  Up to 30 days post-treatment

• MDSC levels

  Up to 30 days post-treatment

• Pazopanib exposure as measured by pharmacokinetics parameters

  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

Study Arms (1)

Treatment (pazopanib hydrochloride and bevacizumab)

EXPERIMENTAL

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.

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

Interventions

Bevacizumab BIOLOGICAL

Given IV

Also known as: Anti-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-VEGF

Treatment (pazopanib hydrochloride and bevacizumab)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (pazopanib hydrochloride and bevacizumab)

Pazopanib Hydrochloride DRUG

Given PO

Also known as: GW786034B, Votrient

Treatment (pazopanib hydrochloride and bevacizumab)

Pharmacological Study OTHER

Correlative studies

Treatment (pazopanib hydrochloride and bevacizumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)-unless patient had a negative stress test within 6 months of screening
• 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

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead
• GlaxoSmithKline: collaborator

Study Sites (5)

The University of Kansas Cancer Center

Westwood, Kansas, 66205, United States

Location

Karamanos Cancer Institute

Detroit, Michigan, 482018, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

Bevacizumab; Immunoglobulin G; Disulfides; pazopanib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immunoglobulin Isotypes; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals

Study Officials

• Saby George

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 24, 2012
• First Posted: September 13, 2012
• Study Start: November 21, 2012
• Primary Completion (Estimated): August 20, 2026
• Study Completion (Estimated): August 20, 2026
• Last Updated: February 27, 2026

Record last verified: 2026-02

Locations

US (5)