Phase
Condition
Carcinoma
Kidney Cancer
Renal Cell Cancer
Treatment
Olaparib
Clinical Study ID
Ages 18-120 All Genders
Study Summary
Eligibility Criteria
Inclusion
Inclusion Criteria:
Willing and able to provide written informed consent. Provision of informed consentis required prior to any study procedures.
Patients aged 18 years of age or older.
Histological proof of renal cell carcinoma (both clear cell and non-clear cellallowed).
Metastatic (AJCC Stage IV) renal cell carcinoma.
Somatic or germline mutation in BAP-1, ATM, BRCA1, BRCA2, PALB2, CHEK2, BRIP1,RAD51C, BARD1, CDK12, CHEK1, FANCL, PP2R2A, RAD51B, RAD51D, or RAD54L as documentedby a clinical CLIA-grade, tissue, saliva or blood-based genetic test.
At least one prior treatment with an anti-angiogenic agent or immune checkpointinhibitor.
Any number of prior systemic therapies is allowed (cytokine, anti-angiogenic, mTOR,immune checkpoint blockage or clinical trial).
Must have measurable disease as defined by RECIST 1.1 criteria.
Participants must have normal organ and bone marrow function measured within 28 daysprior to administration of study treatment as defined below:
Hemoglobin ≥ 10.0 g/dL with no blood transfusion in the past 28 days
Absolute neutrophil count (ANC) ≥ 1.5 x 10^9/L
Platelet count ≥ 100 x 10^9/L
Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN)
Aspartate aminotransferase (AST) (Serum Glutamic Oxaloacetic Transaminase (SGOT)) / Alanine aminotransferase (ALT) (Serum Glutamic Pyruvate Transaminase (SGPT)) ≤ 2.5 x institutional ULN unless liver metastases are present in whichcase they must be ≤ 5 x ULN.
Note: Patients with elevations in bilirubin, AST, or ALT should be thoroughly evaluated for the etiology of this abnormality prior to entry and patients with evidence of viral infection should be excluded.
Patients must have a creatinine clearance ≥ 40 mL/min calculated by Cockroft-Gaultformula or 24 hour urine test.
ECOG PS ≤ 1.
Participants must have a life expectancy ≥ 16 weeks.
Postmenopausal or evidence of non-childbearing status for women of childbearingpotential: negative urine or serum pregnancy test within 28 days of study treatmentand confirmed prior to treatment on day 1.
Postmenopausal is defined as:
Amenorrheic for 1 year or more following cessation of exogenous hormonal treatments.
Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) levels in the postmenopausal range for women under 50 years old.
Radiation-induced oophorectomy with last menses > 1 year ago.
Chemotherapy-induced menopause with > 1 year interval since last menses.
Surgical sterilization (bilateral oophorectomy or hysterectomy).
Male patients must use a condom during treatment and for 3 months after the lastdose of olaparib when having sexual intercourse with a pregnant woman or with awoman of childbearing potential. Female partners of male patients should also use ahighly effective form of contraception if they are of childbearing potential.
Exclusion
Exclusion Criteria:
Other malignancy unless curatively treated with no evidence of disease for ≥ 5 yearsexcept: adequately treated non-melanoma skin cancer, curatively treated in situcancer of the cervix, ductal carcinoma in situ (DCIS), Stage 1, grade 1 endometrialcarcinoma. Patients with a history of localized triple negative breast cancer may beeligible, provided they completed their adjuvant chemotherapy > 3 years prior toregistration, and that the patient remains free of recurrent or metastatic disease.
Patients with symptomatic uncontrolled brain metastases. A scan to confirm theabsence of brain metastases is not required. The patient can receive a stable doseof corticosteroids before and during the study as long as these were started atleast 4 weeks prior to treatment. Patients with spinal cord compression unlessconsidered to have received definitive treatment for this and evidence of clinicallystable disease for 28 days.
Previous allogenic bone marrow transplant or double umbilical cord bloodtransplantation (dUCBT).
Judgment by the investigator that the patient should not participate in the study ifthe patient is unlikely to comply with study procedures, restrictions andrequirements.
Breast feeding women.
Use of any prohibited concomitant medications within the prior 2 weeks.
Involvement in the planning and/or conduct of the study (applies to both AstraZenecastaff and/or staff at the study site).
Participation in another clinical study with an investigational product during thelast 2 weeks.
Patients receiving any systemic chemotherapy or radiotherapy (except for palliativereasons) within 3 weeks prior to study treatment.
Any previous treatment with PARP inhibitor, including olaparib.
Resting ECG with QTc > 500 ms and/or indication of uncontrolled cardiac conditions,as judged by the investigator (e.g. unstable ischemia, uncontrolled symptomaticarrhythmia, congestive heart failure, electrolyte disturbances, etc.), or patientswith congenital and/or family history of long QT syndrome.
Concomitant use of known strong CYP3A inhibitors (e.g. itraconazole, telithromycin,clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir,saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (e.g.ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The requiredwashout period prior to starting olaparib is 2 weeks. During the study, ifco-administration of a strong or moderate inhibitor is required because there is nosuitable alternative medication, exception to this criterion may be allowed with asuitable dose reduction of olaparib.
Concomitant use of known strong CYP3A inducers (e.g. phenobarbital, phenytoin,rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) ormoderate CYP3A inducers (e.g. bosentan, efavirenz, modafinil). The required washoutperiod prior to starting olaparib is 5 weeks for phenobarbital or enzalutamide and 3weeks for other agents.
Persistent toxicities (> Common Terminology Criteria for Adverse Event (CTCAE) grade
- caused by previous cancer therapy, excluding alopecia.
Patients with myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or withfeatures suggestive of MDS/AML.
Major surgery within 2 weeks of starting study treatment and patients must haverecovered from any effects of any major surgery.
Poor medical risk due to a serious, uncontrolled medical disorder, non-malignantsystemic disease or active, uncontrolled infection. Examples include, but are notlimited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardialinfarction, uncontrolled major seizure disorder, extensive interstitial bilaterallung disease on High Resolution Computed Tomography (HRCT) scan or any psychiatricdisorder that prohibits obtaining informed consent.
Unable to swallow orally administered medication and patients with gastrointestinaldisorders likely to interfere with absorption of the study medication.
Immunocompromised patients, e.g., patients who are known to be serologicallypositive for human immunodeficiency virus (HIV).
Known hypersensitivity to olaparib or any of the excipients of the product.
Known active hepatitis (i.e. Hepatitis B or C) due to risk of transmitting theinfection through blood or other body fluids.
No packed red blood cells and/or platelet transfusions within the last 28 days priorto study entry.
Study Design
Study Description
Connect with a study center
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland 21228
United StatesActive - Recruiting
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