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DCE-MRI as Pazopanib Biomarker in Metastatic Renal Cancer

18 Years
Open (Enrolling)
Clear Cell Renal Cell Carcinoma, Recurrent Renal Cell Cancer, Stage IV Renal Cell Cancer

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Trial Information

DCE-MRI as Pazopanib Biomarker in Metastatic Renal Cancer


I. To determine whether a K^trans rise from nadir is predictive of subsequent tumor growth.


I. To determine the association between changes in mean ambulatory blood pressure
measurements, K^trans, and tumor size changes with pazopanib therapy.

II. To determine the association between changes in soluble vascular endothelial growth
factor receptor 2 (sVEGFR2) measurements, K^trans, and tumor size changes with pazopanib


I. To explore previously described single nucleotide polymorphisms (SNP's) as
pharmacogenomic biomarkers.

II. To model tumor growth kinetics using radiologic tumor size measurements. III. To explore
other serum and plasma based putative biomarkers of vascular endothelial growth factor
(VEGF) pathway inhibition.


Patients receive pazopanib hydrochloride orally (PO) once daily (QD) in the absence of
disease progression or unacceptable toxicity. Patients undergo dynamic contrast-enhanced MRI
at baseline, day 8, and prior to courses 3, 5, and 7.

After completion of study treatment, patients are followed up every 3 months for 2 years.

Inclusion Criteria:

- 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; procedures conducted as part of the subject's routine clinical management
(e.g., blood count, imaging study) and obtained prior to signing of informed consent
may be utilized for screening or baseline purposes provided these procedures are
conducted as specified in the protocol

- Histologically confirmed diagnosis of clear cell renal cancer

- Eastern Cooperative Oncology Group (ECOG) performance status of 2 or less

- Measurable disease at least 2 cm in the shortest dimension in the abdomen or pelvis

- No clinical contra-indication to contrast enhanced MRI

- No prior pazopanib therapy

- Archived tumor tissue must be provided for all subjects

- Absolute neutrophil count (ANC) >= 1.5 X 10^9/L

- Hemoglobin >= 9 g/dL (5.6 mmol/L); subjects may not have had a transfusion within 7
days of screening assessment

- Platelets >= 100 X 10^9/L

- Total bilirubin =< 1.5 X upper limit of normal (ULN)

- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 X ULN;
concomitant elevations in bilirubin and AST/ALT above 1.0 x ULN are not permitted

- Estimated glomerular filtration rate (GFR) (modification of renal disease [MDRD]
equation) > 30 ml/min

- Urine protein to creatinine ratio (UPC) < 1; if UPC >= 1, then a 24-hour urine
protein must be assessed; subjects must have a 24-hour urine protein value < 1 g to
be eligible

- 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 < 40 pg/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

- 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; acceptable
contraceptive methods include:

- 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

- Oral contraceptive, either combined or progestogen alone

- Injectable progestogen

- Implants of levonorgestrel

- Estrogenic vaginal ring

- Percutaneous contraceptive patches

- Intrauterine device (IUD) or intrauterine system (IUS) with a documented failure
rate of less than 1% per year

- Male partner sterilization (vasectomy with documentation of azoospermia) prior
to the female subject's entry into the study, and this male is the sole partner
for that subject

- Double barrier method: condom and an occlusive cap (diaphragm or cervical/vault
caps) with a vaginal spermicidal agent (foam/gel/film/cream/suppository)

- Not lactating; female subjects who are lactating should discontinue nursing prior to
the first dose of study drug and should refrain from nursing throughout the treatment
period and for 14 days following the last dose of study drug

Exclusion Criteria:

- Prior malignancy; Note: Subjects who have had another malignancy and have been
disease-free for 3 years, or subjects with a history of completely resected
non-melanomatous skin carcinoma or successfully treated in situ carcinoma are

- History or clinical evidence of central nervous system (CNS) metastases or
leptomeningeal carcinomatosis, except for individuals who have previously-treated CNS
metastases, are asymptomatic, and have had no requirement for steroids or
anti-seizure medication for 6 months prior to first dose of study drug; screening
with CNS imaging studies (computed tomography [CT] or MRI) is required only if
clinically indicated or if the subject has a history of CNS metastases

- Clinically significant gastrointestinal abnormalities that may increase the risk for
gastrointestinal bleeding including, but not limited to:

- Active peptic ulcer disease

- Known intraluminal metastatic lesion/s with risk of 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

- Presence of uncontrolled infection

- Corrected QT interval (QTc) > 480 msecs using Bazett's formula

- 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)

- Poorly controlled hypertension (defined as systolic blood pressure (SBP) of >=
140 mmHg or diastolic blood pressure [DBP] of >= 90 mmHg); Note: Initiation or
adjustment of antihypertensive medication(s) is permitted prior to study entry;
blood pressure (BP) must be re-assessed on two occasions that are separated by a
minimum of 1 hour; on each of these occasions, the mean (of 3 readings) SBP/DBP
values from each BP assessment must be < 140/90 mmHg in order for a subject to
be eligible for the study

- History of cerebrovascular accident including transient ischemic attack (TIA),
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)

- Evidence of active bleeding or bleeding diathesis

- Known endobronchial lesions and/or lesions infiltrating major pulmonary vessels

- Hemoptysis in excess of 2.5 mL (or one half teaspoon) within 8 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

- Treatment with any of the following therapies:

- Radiation therapy, surgery or tumor embolization within 14 days prior to the first
dose of pazopanib OR

- Anti-cancer chemotherapy, immunotherapy, biologic therapy, investigational therapy or
hormonal therapy within 14 days or five half-lives of a drug (whichever is longer)
prior to the first dose of pazopanib

- Any non-oncologic investigational drug within 30 days or 5 half lives whichever is
longer prior to receiving the first dose of study treatment

- Any ongoing toxicity from prior anti-cancer therapy that is > grade 1 and/or
that is progressing in severity, except alopecia

Type of Study:


Study Design:

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

Outcome Measure:

Disease progression based on change in K^trans rise from nadir as assessed by the method described in Donner

Outcome Description:

Cox proportional hazards model incorporating a baseline clinical prognostic index (good/intermediate/poor) and prior VEGF pathway inhibitor therapy (yes/no) as covariates will be assessed.

Outcome Time Frame:

Up to 2 years

Safety Issue:


Principal Investigator

Walter Stadler

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Chicago Comprehensive Cancer Center


United States: Institutional Review Board

Study ID:




Start Date:

August 2012

Completion Date:

June 2015

Related Keywords:

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



University of Chicago Comprehensive Cancer Center Chicago, Illinois  60637-1470