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A Phase II Study of Pazopanib to Enable Partial Nephrectomy


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Clear Cell Renal Cell Carcinoma, Stage I Renal Cell Cancer, Stage II Renal Cell Cancer, Stage III Renal Cell Cancer

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Trial Information

A Phase II Study of Pazopanib to Enable Partial Nephrectomy


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.

Inclusion 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

- 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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Rate of partial nephrectomy in patients with primary renal tumors otherwise requiring radical nephrectomy

Outcome Time Frame:

Partial nephrectomy performed after 1 week off pazopanib (continue pazopanib until 1 week prior to surgery)

Safety Issue:

No

Principal Investigator

Brian Rini

Investigator Role:

Principal Investigator

Investigator Affiliation:

Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center

Authority:

United States: Institutional Review Board

Study ID:

CASE4809

NCT ID:

NCT01158521

Start Date:

June 2010

Completion Date:

Related Keywords:

  • Clear Cell Renal Cell Carcinoma
  • Stage I Renal Cell Cancer
  • Stage II Renal Cell Cancer
  • Stage III Renal Cell Cancer
  • Carcinoma
  • Carcinoma, Renal Cell

Name

Location

Fox Chase Cancer CenterPhiladelphia, Pennsylvania  19111
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer CenterCleveland, Ohio  44106-5065
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer CenterCleveland, Ohio  44195