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.
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.
Other malignancy unless curatively treated with no evidence of disease for ≥ 5 years except: adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS), Stage 1, grade 1 endometrial carcinoma. Patients with a history of localized triple negative breast cancer may be eligible, provided they completed their adjuvant chemotherapy > 3 years prior to registration, and that the patient remains free of recurrent or metastatic disease.
Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absence of brain metastases is not required. The patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 4 weeks prior to treatment. Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days.
Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT).
Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements.
Single group
Olaparib
DrugOlaparib 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.
Objective Response or Stable Disease to Olaparib Therapy at Six Months
Complete response (CR) or partial response (PR) at any time on study or stable disease (SD) after 6 months of Olaparib treatment, based on RECIST 1.1 criteria.
Safety of Olaparib Therapy As Determined by the Number of Adverse Events
Number of Adverse Events, Grade 3 or higher as defined by Common Terminology Criteria for Adverse Events (CTCAE) v5.0
Median Progression-Free Survival to Olaparib Therapy
Number of months from the time of initiation on Olaparib therapy until radiographic progression or death, whichever comes first while enrolled on the study, based on RECIST 1.1 criteria.
Rate of Objective Response to Olaparib Therapy
Number of participants with best overall response (complete response (CR) or partial response (PR)) at anytime on study.
Reversion Mutations in Circulating Tumor DNA (ctDNA) at Clinical Progression
Number of incidences of reversion mutations in circulating tumor DNA (ctDNA) at time of clinical progression.
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Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Lead sponsor
AstraZeneca
Collaborator
