Pazopanib Hydrochloride Before Surgery in Treating Patients With Kidney Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Case Comprehensive Cancer Center
Sponsor:
Information provided by (Responsible Party):
Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT01158521
First received: July 1, 2010
Last updated: July 17, 2014
Last verified: July 2014
  Purpose

RATIONALE: Pazopanib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving pazopanib hydrochloride before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

PURPOSE: This phase II trial is studying how well pazopanib hydrochloride works when given before surgery in treating patients with kidney cancer.


Condition Intervention Phase
Clear Cell Renal Cell Carcinoma
Stage I Renal Cell Cancer
Stage II Renal Cell Cancer
Stage III Renal Cell Cancer
Drug: pazopanib hydrochloride
Procedure: therapeutic conventional surgery
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Pazopanib to Enable Partial Nephrectomy

Resource links provided by NLM:


Further study details as provided by Case Comprehensive Cancer Center:

Primary Outcome Measures:
  • Rate of partial nephrectomy in patients with primary renal tumors otherwise requiring radical nephrectomy [ Time Frame: Partial nephrectomy performed after 1 week off pazopanib (continue pazopanib until 1 week prior to surgery) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Number of Participants with above grade 2 Adverse Events as a Measure of Safety and Tolerability [ Time Frame: every 4 week cycle ] [ Designated as safety issue: Yes ]
    Pazopanib dose may be adjusted according to individual patient tolerance. Toxicity will be monitored continuously and consideration will be given to stopping the trial early if >2 of the first 8 patients or >3 of the first 12 experience serious treatment-related toxicity (defined as grade 4 toxicity or discontinuation of drug due to toxicity) or unexpected surgical morbidity. With these guidelines the likelihood of stopping the trial after the first 8 (12) patients is >74% (>86%) if the underlying risk of serious toxicity is >30% and <6% (<6%) if the risk is <5%.

  • Tumor diameter/volume change [ Time Frame: at end of week 8 ] [ Designated as safety issue: No ]
    Tumor size reduction ≥ 30%

  • Conversion of hilar to non-hilar tumors [ Time Frame: at end of week 8 ] [ Designated as safety issue: No ]
    Conversion of tumor post therapy so that there is < 10% risk that a partial nephrectomy would be associated with a high risk of significant postoperative morbidity (e.g. conversion of tumor post therapy to ≥ 3 mm away from renal hilum (main renal artery, renal vein, or primary branches)

  • surgical morbidity [ Time Frame: post-surgery ] [ Designated as safety issue: Yes ]
    Conversion of tumor post therapy so that there is < 10% risk that a partial nephrectomy would be associated with a high risk of significant postoperative morbidity (e.g. conversion of tumor post therapy to ≥ 3 mm away from renal hilum (main renal artery, renal vein, or primary branches)


Estimated Enrollment: 30
Study Start Date: June 2010
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive oral pazopanib hydrochloride once daily for up to 18 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo either partial or radical nephrectomy at least 7 days after completion of pazopanib hydrochloride.
Drug: pazopanib hydrochloride
Oral pazopanib hydrochloride once daily for up to 18 weeks in the absence of disease progression or unacceptable toxicity.
Other Names:
  • GW786034
  • Votrient
Procedure: therapeutic conventional surgery
Patients undergo either partial or radical nephrectomy at least 7 days after completion of pazopanib hydrochloride.

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine the rate of partial nephrectomy in patients with primary renal tumors otherwise requiring radical nephrectomy after neoadjuvant pazopanib treatment.

SECONDARY OBJECTIVES:

I. To determine the safety, tumor diameter/volume change, conversion of hilar to non-hilar tumors and surgical morbidity of neoadjuvant pazopanib for renal cell carcinoma (RCC).

OUTLINE:

Patients receive oral pazopanib hydrochloride once daily for up to 18 weeks in the absence of disease progression or unacceptable toxicity. Patients undergo either partial or radical nephrectomy at least 7 days after completion of pazopanib hydrochloride.

After completion of study treatment, patients are followed up for 1 year.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion

  • Histologically or cytologically proven renal carcinoma with a clear cell component
  • Total tumor size >= 4.0 cm (largest tumor diameter or sum of largest tumor diameters if more than one tumor)
  • Need for optimized partial nephrectomy based on one or more of the following criteria (all applicable criteria should be recorded and one criterion designated as the primary reason):

    • Functional or anatomic solitary kidney, bilateral tumors, or pre-existing chronic kidney disease (CKD; estimated GFR by Cockcroft-Gault formula < 60 mL/min) and tumor amenable to partial nephrectomy, but partial nephrectomy would result in estimated GFR < 30 mL/min; this estimation will be based on current estimated GFR, nuclear renal scan to estimate relative renal function (if 2 kidneys), tumor location(s), and amount of normal renal parenchyma that would need to be removed with nephrectomy
    • Radical nephrectomy is required for tumor excision; however, it would result in estimated GFR < 30 mL/min; this estimation will be based on current estimated GFR, nuclear renal scan to estimate relative renal function (if 2 kidneys), tumor location(s), and amount of normal renal parenchyma that would need to be removed with radical nephrectomy
    • Greater than 30% likelihood that a partial nephrectomy would be associated with a high risk of significant morbidity (e.g. hemorrhage) due to proximity to the renal hilum (within 3 mm of main renal artery, renal vein or their primary branches) and/or other anatomic factors as determined by the operating surgeon
    • Renal nephrometry score of 10-12
  • ECOG performance status 0 or 1
  • Karnofsky >= 70%
  • Serum aspartate transaminase (AST; serum glutamic oxaloacetic transaminase [SGOT]) =< 2.5 x laboratory upper limit of normal (ULN)
  • Serum alanine transaminase (ALT; serum glutamic pyruvic transaminase [SGPT]) =< 2.5 x laboratory upper limit of normal (ULN)
  • Total serum bilirubin =< 1.5 x ULN
  • Absolute neutrophil count (ANC) >= 1500/uL
  • Platelets >= 100,000/uL
  • Hemoglobin >= 9.0 g/dL (no transfusion permitted within 1 week)
  • Serum creatinine =< 2.5 mg/dL
  • Urine to protein to creatinine (UPC) ratio < 1; if UPC > 1, then a 24-hour urine protein must be assessed; subjects must have a 24-hour urine protein value < 1g to be eligible
  • Prothrombin time (PT) or international normalized ratio (INR) and partial thromboplastin time (PTT) =< 1.2 X upper limit of normal (ULN)
  • Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures; subjects must provide written informed consent prior to performance of study-specific procedures or assessments, and must be willing to comply with treatment and follow up
  • A female is eligible to enter and participate in this study if she is of:
  • Non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female who has had: a hysterectomy; a bilateral oophorectomy (ovariectomy); a bilateral tubal ligation; is post-menopausal
  • Subjects not using hormone replacement therapy (HRT) must have experienced total cessation of menses for >= 1 year and be greater than 45 years in age, OR, in questionable cases, have a follicle stimulating hormone (FSH) value > 40 mIU/mL and an estradiol value < 40pg/mL (< 140 pmol/L)
  • Subjects using HRT must have experienced total cessation of menses for >= 1 year and be greater than 45 years of age OR have had documented evidence of menopause based on FSH and estradiol concentrations prior to initiation of HRT
  • Childbearing potential, including any female who has had a negative serum pregnancy test within 2 weeks prior to the first dose of study treatment, preferably as close to the first dose as possible, and agrees to use adequate contraception; GSK acceptable contraceptive methods, when used consistently and in accordance with both the product label and the instructions of the physician, are as follows: an intrauterine device with a documented failure rate of less than 1% per year; vasectomized partner who is sterile prior to the female subject's entry and is the sole sexual partner for that female; complete abstinence from sexual intercourse for 14 days before exposure to investigational product, through the dosing period, and for at least 21 days after the last dose of investigational product; or double-barrier contraception (condom with spermicidal jelly, foam suppository, or film; diaphragm with spermicide; or male condom and diaphragm with spermicide)

Exclusion

  • Prior systemic treatment for RCC
  • Evidence of any distant metastatic disease
  • Evidence of bleeding diathesis or coagulopathy; patients with hematuria from the primary renal tumor are eligible provided all other eligibility criteria are met
  • History of any one or more of the following cardiovascular conditions within the past 6 months: cardiac angioplasty or stenting; myocardial infarction; unstable angina; coronary artery bypass graft surgery; symptomatic peripheral vascular disease
  • Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA)
  • Prolongation of corrected QT interval (QTc) > 480 msecs
  • Hypertension that cannot be controlled by medications to < 160/90 mmHg
  • History of cerebrovascular accident, pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months (Note: subjects with recent DVT who have been treated with therapeutic anti-coagulating agents for at least 6 weeks are eligible)
  • Prior major surgery or trauma within 28 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement not considered to be major)
  • Hemoptysis within 6 weeks of first dose of study drug
  • Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures
  • Unable or unwilling to discontinue use of prohibited medications for at least 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of study drug and for the duration of the study
  • Clinically significant gastrointestinal abnormalities that may increase the risk for GI bleeding including, but not limited to: active peptic ulcer disease; known intraluminal metastatic lesion/s with suspected bleeding; inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease), or other gastrointestinal conditions with increased risk of perforation; history of abdominal fistula, gastrointestinal perforation, or intra abdominal abscess within 28 days prior to beginning study treatment
  • Clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to: malabsorption syndrome; major resection of the stomach or small bowel
  • Prior major surgery or trauma (NOT including biopsy of renal mass; also procedures such as catheter placement not considered to be major) within 28 days prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer
  • Presence of uncontrolled infection
  • Other severe acute or chronic medical or psychiatric conditions or laboratory abnormality that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, and in the judgment of the investigator would make the patient inappropriate for entry into this study
  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: NCT01158521

Locations
United States, Ohio
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center Recruiting
Cleveland, Ohio, United States, 44195
Contact: Brian I. Rini    216-445-9567    rinib2@ccf.org   
Principal Investigator: Brian I. Rini         
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center Withdrawn
Cleveland, Ohio, United States, 44106
United States, Pennsylvania
Fox Chase Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19111
Contact: David Chen, MD    215-728-2548    david.chen@fccc.edu   
Sponsors and Collaborators
Case Comprehensive Cancer Center
Investigators
Principal Investigator: Brian Rini Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
  More Information

No publications provided

Responsible Party: Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01158521     History of Changes
Other Study ID Numbers: CASE4809, NCI-2010-01392
Study First Received: July 1, 2010
Last Updated: July 17, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases

ClinicalTrials.gov processed this record on August 19, 2014