Study of Olaparib in Metastatic Renal Cell Carcinoma Patients With DNA Repair Gene Mutations (ORCHID)

  • STATUS
    Recruiting
  • End date
    Mar 21, 2023
  • participants needed
    20
  • sponsor
    Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Updated on 9 February 2022
platelet count
iron
hysterectomy
serum pregnancy test
cytokines
measurable disease
carcinoma
vegf
oophorectomy
metastasis
neutrophil count
liver metastasis
bevacizumab
olaparib
BRCA1
ATM
BRCA2
vascular endothelial growth factor
immune checkpoint inhibitor
CDK12
palb2
fancl
rad51c
BRIP1
CHEK2
BARD1
BAP1
RAD51B
CHEK1
RAD51D
metastatic renal cell carcinoma
PP2R2A
BAP-1
RAD54L

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 progression according to RECIST 1.1 criteria or unmanageable toxicity requiring cessation.

Details
Condition Renal Cell Carcinoma, Metastatic Renal Cell Carcinoma, Kidney Cancer, Renal Carcinoma, Kidney Cancer Metastatic
Treatment olaparib
Clinical Study IdentifierNCT03786796
SponsorSidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Last Modified on9 February 2022

Eligibility

Yes No Not Sure

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 with an anti-angiogenic agent or immune checkpoint inhibitor
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 days prior 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 which case 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 51 mL/min calculated by Cockroft-Gault formula 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 childbearing potential: negative urine or serum pregnancy test within 28 days of study treatment and 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 post menopausal 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 last dose of olaparib when having sexual intercourse with a pregnant woman or with a woman of childbearing potential. Female partners of male patients should also use a highly effective form of contraception if they are of childbearing potential

Exclusion Criteria

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
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 AstraZeneca staff and/or staff at the study site)
Participation in another clinical study with an investigational product during the last 2 weeks
Patients receiving any systemic chemotherapy or radiotherapy (except for palliative reasons) 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 symptomatic arrhythmia, congestive heart failure, electrolyte disturbances, etc.), or patients with 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 required washout period prior to starting olaparib is 2 weeks. During the study, if co-administration of a strong or moderate inhibitor is required because there is no suitable alternative medication, exception to this criterion may be allowed with a suitable 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) or moderate CYP3A inducers (e.g. bosentan, efavirenz, modafinil). The required washout period prior to starting olaparib is 5 weeks for phenobarbital or enzalutamide and 3 weeks for other agents
Persistent toxicities (> Common Terminology Criteria for Adverse Event (CTCAE) grade 2) caused by previous cancer therapy, excluding alopecia
Patients with myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or with features suggestive of MDS/AML
Major surgery within 2 weeks of starting study treatment and patients must have recovered from any effects of any major surgery
Poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, extensive interstitial bilateral lung disease on High Resolution Computed Tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent
Unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication
Immunocompromised patients, e.g., patients who are known to be serologically positive 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 the infection through blood or other body fluids
No packed red blood cells and/or platelet transfusions within the last 28 days prior to study entry
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