Phase II Study of Olaparib in Metastatic Renal Cell Carcinoma Patients Harboring a BAP-1 or Other DNA Repair Gene Mutations (ORCHID)
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Summary
Single arm, single site, open-label Phase II study of the effects of oral olaparib in participants with metastatic renal cell carcinoma that harbor an inactivating mutation in BAP-1, ATM, BRCA1, BRCA2, PALB2, CHEK2, BRIP1, RAD51C, BARD1, CDK12, CHEK1, FANCL, PP2R2A, RAD51B, RAD51D, or RAD54L who have had prior treatment with at least one immune checkpoint inhibitor or anti-VEGF therapy. Must have measurable disease on CT imaging per RECIST 1.1 criteria.
Description
The trial will enroll up to 20 participants. Following enrollment, participants will be initially treated with olaparib 150mg by mouth twice daily for one month. After one month of therapy, the dose of olaparib will be increased to 300mg by mouth twice daily provided there are no grade 3 or greater adverse events experienced. All participants will be reassessed at least monthly for toxicity, including laboratory investigations. Radiological scans will be performed approximately every 3 months to assess for disease response. Treatment will be continued until clinical and/or radiographic progres…
Eligibility
- Age range
- 18–120 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Willing and able to provide written informed consent. Provision of informed consent is 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 cell allowed). * 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 documented by a clinical CLIA-grade, tissue, saliva or blood-based genetic test. * At least one prior treatment…
Interventions
- DrugOlaparib
Olaparib is a crystalline solid, is non-chiral and shows pH-independent solubility of approximately 0.1 mg/mL across the physiological range. Olaparib is presented for oral administration as a green, film-coated tablet containing 25 mg, 100 mg or 150 mg of drug substance. The 100 mg strength is also available as a yellow, film-coated tablet. The 25 mg, 100 mg and 150 mg strengths of olaparib tablets are composed of the same constituents. The tablet cores comprise: olaparib, copovidone, colloidal silicon dioxide, mannitol and sodium stearyl fumarate. The composition of the green tablet film coating is: hydroxypropyl methylcellulose (hypromellose), macrogol 400 (polyethylene glycol 400), titanium dioxide, iron oxide yellow and iron oxide black. The yellow tablet film coating only differs from the green film coating with the omission of iron oxide black.
Location
- Johns Hopkins Sidney Kimmel Comprehensive Cancer CenterBaltimore, Maryland