Dynamic Contrast-Enhanced MRI and Ultrasound in Measuring Tumor Perfusion Changes in Patients With Kidney Cancer That is Metastatic or Cannot Be Removed by Surgery Receiving Pazopanib Hydrochloride
All patients who participate in this study will receive pazopanib (pazopanib hydrochloride). Pazopanib is an oral drug (pill) that has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of advanced kidney cancer. In this study, researchers plan to learn more about the way this drug works by using special scans (magnetic resonance imaging [MRIs] and ultrasounds) to help evaluate how this drug is working on kidney cancer.
- 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 * Note: it is not necessary that informed consent be obtained within the protocol specified screening window
- Diagnosis of unresectable and/or metastatic clear cell renal cell carcinoma; 10 patients will be enrolled who have had no prior anti-angiogenic therapy; 10 patients will be enrolled who have had one prior anti-angiogenic therapy
- Prior radiation therapy to a symptomatic site of metastatic disease is allowed but patients must have discontinued/completed radiation therapy at least 2 weeks prior to entering the study, and have recovered from adverse events due to that treatment
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
- Patients must have measureable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
- Archived tumor blocks must be provided for all subjects for correlative analysis before or during treatment with pazopanib
- Absolute neutrophil count (ANC) >= 1.5 X 10^9/L (evaluated within 28 days of randomization)
- Hemoglobin >= 9 g/dL (5.6 mmol/L) (evaluated within 28 days of randomization); subjects may not have had a transfusion within 7 days of screening assessment
- Platelets >= 100 X 10^9/L (evaluated within 28 days of randomization)
- Prothrombin time (PT) or international normalized ratio (INR) =< 1.2 X upper limit of normal (ULN) (evaluated within 28 days of randomization); subjects receiving anticoagulant therapy are eligible if their INR is stable and within the recommended range for the desired level of anticoagulation
- Partial thromboplastin time (PTT) =< 1.2 X ULN (evaluated within 28 days of randomization)
- Total bilirubin =< 1.5 X ULN (evaluated within 28 days of randomization); concomitant elevations in bilirubin and aspartate amino transferase (AST)/alanine aminotransferase (ALT) above 1.0 x ULN are not permitted
- AST and ALT =< 2.5 X ULN or =< 5 x ULN if liver metastases are present (evaluated within 28 days of randomization); concomitant elevations in bilirubin and AST/ALT above 1.0 x ULN are not permitted
- Serum creatinine =< 1.5 mg/dL (133 umol/L), or, if greater than 1.5 mg/dL: calculated creatinine clearance >= 50 mL/min (evaluated within 28 days of randomization)
- Urine protein to creatinine ratio (UPC) < 1 (evaluated within 28 days of randomization); 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
- Patients must not receive any other investigational agents while on study
- Patients must not be taking cytochrome P450 enzyme-inducing antiepileptic drugs (phenytoin, carbamazepine or phenobarbital), rifampin or St. John’s wort
- Females are 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; GlaxoSmithKline (GSK) acceptable contraceptive methods, when used consistently and in accordance with both the product label and the instructions of the physician, are as follow: ** 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 ** Double-barrier contraception (condom with spermicidal jelly, foam suppository, or film; diaphragm with spermicide; or male condom and diaphragm with spermicide) ** Oral contraceptives
- 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
- Women must not be pregnant or breast-feeding as the agents used in this study may be teratogenic to a fetus and there is no information on the excretion of the agents or their metabolites into breast milk; all females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy
- Patients must not have active 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 eligible
- Patients must not have a 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 magnetic resonance imaging [MRI]) is required only if clinically indicated or if the subject has a history of CNS metastases
- Patients must not have 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
- Patients must not have 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
- Patients must not have presence of uncontrolled infection
- Patient must not have corrected QT interval (QTc) > 480 msecs using Bazett’s formula
- Patients must not have 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)
- Patient must not have poorly controlled hypertension (defined as systolic blood pressure [SBP] of >= 140 mmHg or diastolic blood pressure [DBP] of >= 90mmHg) * Note: Initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry; 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 prior to study enrollment)
- Patient must not have 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
- Patient must not have 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)
- Patient must not have evidence of active bleeding or bleeding diathesis
- Patient must not have known endobronchial lesions and/or lesions infiltrating major pulmonary vessels
- Patient must not have hemoptysis within 6 weeks of first dose of study drug
- Patient must not have 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
- Patient must not be 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
- Must not have treatment with any of the following anti-cancer therapies: * Radiation therapy, surgery or tumor embolization within 14 days prior to the first dose of pazopanib OR * Chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal therapy within 14 days prior to the first dose of pazopanib * Treatment with prior sorafenib, sunitinib, temsirolimus or everolimus is allowed but must be discontinued at least 5 days prior to beginning pazopanib
- Patient must not have any ongoing toxicity from prior anti-cancer therapy that is > grade 1 and/or that is progressing in severity, except alopecia
Locations & Contacts
Contact: Naomi Susanne Balzer-Haas
Phone: 215-662-2812 Email: firstname.lastname@example.org
Trial Objectives and Outline
I. Assessment of early changes in dynamic contrast enhanced (DCE)-MRI and ultrasound measures of tumor perfusion in the setting of pazopanib therapy for patients with metastatic clear cell renal cell carcinoma.
I. Correlation of baseline DCE-MRI and ultrasound parameters and clinical outcome.
II. Correlation of early (48 +/- 24 hr after treatment) changes in DCE-MRI and ultrasound parameters and clinical outcome.
III. Correlation of baseline (and changes) in DCE-MRI and ultrasound parameters with von Hippel-Lindau (VHL) status in tumors and histocytometric analysis of endothelial cell activation in archival nephrectomy specimens.
IV. Provide an insight in the respective predictive values of DCE-MRI and ultrasound (US) for pazopanib treatment.
Patients receive pazopanib hydrochloride orally (PO) once daily (QD) on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo DCE-MRI and ultrasound imaging prior to the start of pazopanib hydrochloride, 48 hours post-initiation of pazopanib hydrochloride, and after 3-4 weeks on the study drug.
After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 1 year.
Trial Phase & Type
No phase specified
University of Pennsylvania / Abramson Cancer Center
Naomi Susanne Balzer-Haas
Secondary IDs NCI-2012-00754
Clinicaltrials.gov ID NCT01221506