This study is NOT currently recruiting participants.
Number
07-C-0121
Sponsoring Institute
National Cancer Institute (NCI)
Recruitment Detail
Type: Completed Study; data analyses ongoing Gender: Male & Female Min Age: 18 Years Max Age: N/A
Referral Letter Required
No
Population Exclusion(s)
Children;Fetuses;Pregnant Women
Keywords
Kidney Cancer; Hereditary Papillary Renal Cell Carcinoma; Tyrosine Kinase Inhibitor; Hereditary
Recruitment Keyword(s)
None
Condition(s)
Papillary Renal Cell Carcinoma; Hereditary Papillary Renal Cancer; Carcinoma, Renal Cell
Investigational Drug(s)
Foretinib (Formerly GSK1363089 or XL880)
Investigational Device(s)
Intervention(s)
Drug: Foretinib
Supporting Site
National Cancer Institute, Elelixis Inc.
-A type of kidney cancer called papillary renal cell carcinoma (PRC) is the second most common form of kidney cell cancer.
-PRC can occur in families as an inherited condition or randomly in the population. PRC is thought to involve increased activity of a protein called c-Met located on the cell surface. Genetic alterations (mutations) in the c-Met gene are responsible for the inherited form of one kind of papillary kidney cancer.
-GSK1363089 is a drug that blocks the c-Met protein and might decrease the tumor s ability to grow. The drug might also interfere with tumor growth by blocking proteins that help provide blood supply to tumors.
Objectives:
-To evaluate whether GSK1363089 is safe, effective and well tolerated in patients with PRC.
-To learn how the body handles GSK1363089.
Eligibility:
-Patients 18 years of age or older with Papillary RenalCancer in either the kidneys or metastatic (the cancer has spread to other organs).
Design:
-Patients are assigned to one of two study groups: Group A includes approximately 15 patients with one or more of the c-Met mutations in their blood cells; group B includes approximately 15 patients with no evidence of c-Met mutations. Patients in both study groups will receive GSK1363089.
-Patients take GSK1363089 by mouth on 2-week treatment cycles of 5 days on drug and 9 days off drug for 8 weeks. The effect of the drug on tumors is assesses approximately every 8 weeks by CT or MRI scans. Patients whose disease does not get worse and who tolerate the drug may continue treatment for up to 1 year or longer..
-Patients are tested for the c-Met gene alteration. They meet with a genetic counselor before the test to discuss the risks of genetic testing. Patients who are found to have an inherited form of PRC meet with a genetic counselor again to discuss the condition and implications for the patient and other family members.
-During the study, patients come to the NIH clinic periodically for physical examinations, CT scans, blood and urine tests and electrocardiograms.
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INCLUSION CRITERIA: A subject must meet the following criteria to be eligible for the study: 1. The subject must have a histologically confirmed diagnosis of PRC manifest as either metastatic disease or bilateral multifocal renal tumors localized to the kidneys, excepting subjects with bilateral, multifocal renal tumors with a documented germline c-MET mutation consistent with hPRC who may be enrolled without a tissue diagnosis. 2. The subject has measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as greater than or equal to 20 mm with conventional techniques, or as greater than or equal to 10 mm with spiral computerized tomography (CT) scan. 3. The subject is at least 18 years old. 4. The subject has an ECOG performance status less than or equal to 2. 5. The subject has unstained slides of tumor tissue, archival or from a recent biopsy, or paraffin block available for c-MET pathway analysis (excepting subjects with bilateral, multifocal renal tumors with a documented c-MET mutation consistent with hPRC, who may be enrolled without tissue as described above if such samples do not exist). 6. When exposed to the adrenocorticotropic hormone (ACTH) stimulation test, the subject has a serum cortisol level greater than or equal to 20 microg/dL (552 nmol/L) 30-90 minutes after injection of ACTH. 7. The subject has a QTcB (Bazett corrected) or QTcF (Frederica corrected) less than 470 msec. If the first ECG reading is greater than or equal to 470 msec, repeat the ECG twice over a 10 minute period. Then use the average QTc value to determine whether the subject can be included. 8. The subject has organ and marrow function as follows: absolute neutrophil count (ANC) greater than or equal to 1500/mm(3), platelets greater than or equal to 100,000/mm(3), hemoglobin greater than or equal to 9 g/dL, bilirubin less than or equal to 1.5 mg/dL or less than or equal to 1.5 times ULN if no liver involvement (or less than or equal to 2 mg/dL or less than or equal to 2 times ULN with liver involvement), serum creatinine less than or equal to 2.0 mg/dL and calculated creatinine clearance greater than or equal to 50 mL/min, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 2.5 times the upper limit of normal if no liver involvement or less than or equal to 5 times the upper limit of normal with liver involvement. 9. The subject is capable of understanding and complying with the protocol and has signed the informed consent document. 10. Sexually active subjects must use an accepted method of contraception during the course of the study. 11. Female patients of childbearing potential must have a negative pregnancy test at enrollment. 12. The subject has had no other diagnosis of malignancy (unless non-melanoma skin cancer or a malignancy diagnosed greater than 5 years ago with no current evidence of disease). EXCLUSION CRITERIA: A subject who meets any of the following criteria is ineligible for the study: 1. The subject has received radiation to greater than or equal to 25% of his or her bone marrow within 14 days of GSK1363089 treatment. 2. The subject has received more than 1 prior anticancer therapy. 3. The subject has received any systemic anticancer therapy, including cytotoxic chemotherapy, anti-VEGF, anti-VEGFR agents, or investigational drug within 14 days of the first dose of study drug. 4. The subject has received an inhibitor of c-MET (eg, antibodies to HGF, small molecule inhibitors of c-MET). 5. The subject has not recovered to NCI CTCAE v3.0 Grade less than or equal to 1 from AEs due to investigational drugs or other medications that were administered more than 14 days before study enrollment. 6. The subject has known brain metastases. 7. The subject has uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. For the purposes of this protocol, hypertension will be considered uncontrolled if despite optimal antihypertensive therapy either the systolic blood pressure (SBP) is greater than 140 mm Hg or diastolic blood pressure (DBP) is greater than 90 mm Hg for a sustained period of time (greater than 24 hours) or results in symptoms. 8. The subject is pregnant or breastfeeding. 9. The subject is known to be positive for the human immunodeficiency virus (HIV) and is receiving antiretroviral therapies. Subjects known to be HIV positive who do not require antiretroviral therapy will be eligible if they meet other entry criteria. 10. The subject has an allergy or hypersensitivity to components of the GSK1363089 formulation. 11. The subject has an inability or unwillingness to abide by the study protocol or cooperate fully with the investigator or designee.
A subject must meet the following criteria to be eligible for the study:
1. The subject must have a histologically confirmed diagnosis of PRC manifest as either metastatic disease or bilateral multifocal renal tumors localized to the kidneys, excepting subjects with bilateral, multifocal renal tumors with a documented germline c-MET mutation consistent with hPRC who may be enrolled without a tissue diagnosis.
2. The subject has measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as greater than or equal to 20 mm with conventional techniques, or as greater than or equal to 10 mm with spiral computerized tomography (CT) scan.
3. The subject is at least 18 years old.
4. The subject has an ECOG performance status less than or equal to 2.
5. The subject has unstained slides of tumor tissue, archival or from a recent biopsy, or paraffin block available for c-MET pathway analysis (excepting subjects with bilateral, multifocal renal tumors with a documented c-MET mutation consistent with hPRC, who may be enrolled without tissue as described above if such samples do not exist).
6. When exposed to the adrenocorticotropic hormone (ACTH) stimulation test, the subject has a serum cortisol level greater than or equal to 20 microg/dL (552 nmol/L) 30-90 minutes after injection of ACTH.
7. The subject has a QTcB (Bazett corrected) or QTcF (Frederica corrected) less than 470 msec. If the first ECG reading is greater than or equal to 470 msec, repeat the ECG twice over a 10 minute period. Then use the average QTc value to determine whether the subject can be included.
8. The subject has organ and marrow function as follows: absolute neutrophil count (ANC) greater than or equal to 1500/mm(3), platelets greater than or equal to 100,000/mm(3), hemoglobin greater than or equal to 9 g/dL, bilirubin less than or equal to 1.5 mg/dL or less than or equal to 1.5 times ULN if no liver involvement (or less than or equal to 2 mg/dL or less than or equal to 2 times ULN with liver involvement), serum creatinine less than or equal to 2.0 mg/dL and calculated creatinine clearance greater than or equal to 50 mL/min, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal to 2.5 times the upper limit of normal if no liver involvement or less than or equal to 5 times the upper limit of normal with liver involvement.
9. The subject is capable of understanding and complying with the protocol and has signed the informed consent document.
10. Sexually active subjects must use an accepted method of contraception during the course of the study.
11. Female patients of childbearing potential must have a negative pregnancy test at enrollment.
12. The subject has had no other diagnosis of malignancy (unless non-melanoma skin cancer or a malignancy diagnosed greater than 5 years ago with no current evidence of disease).
EXCLUSION CRITERIA:
A subject who meets any of the following criteria is ineligible for the study:
1. The subject has received radiation to greater than or equal to 25% of his or her bone marrow within 14 days of GSK1363089 treatment.
2. The subject has received more than 1 prior anticancer therapy.
3. The subject has received any systemic anticancer therapy, including cytotoxic chemotherapy, anti-VEGF, anti-VEGFR agents, or investigational drug within 14 days of the first dose of study drug.
4. The subject has received an inhibitor of c-MET (eg, antibodies to HGF, small molecule inhibitors of c-MET).
5. The subject has not recovered to NCI CTCAE v3.0 Grade less than or equal to 1 from AEs due to investigational drugs or other medications that were administered more than 14 days before study enrollment.
6. The subject has known brain metastases.
7. The subject has uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. For the purposes of this protocol, hypertension will be considered uncontrolled if despite optimal antihypertensive therapy either the systolic blood pressure (SBP) is greater than 140 mm Hg or diastolic blood pressure (DBP) is greater than 90 mm Hg for a sustained period of time (greater than 24 hours) or results in symptoms.
8. The subject is pregnant or breastfeeding.
9. The subject is known to be positive for the human immunodeficiency virus (HIV) and is receiving antiretroviral therapies. Subjects known to be HIV positive who do not require antiretroviral therapy will be eligible if they meet other entry criteria.
10. The subject has an allergy or hypersensitivity to components of the GSK1363089 formulation.
11. The subject has an inability or unwillingness to abide by the study protocol or cooperate fully with the investigator or designee.
Principal Investigator
Referral Contact
For more information: