- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03786796
Study of Olaparib in Metastatic Renal Cell Carcinoma Patients With DNA Repair Gene Mutations (ORCHID)
March 4, 2024 updated by: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Phase II Study of Olaparib in Metastatic Renal Cell Carcinoma Patients Harboring a BAP-1 or Other DNA Repair Gene Mutations (ORCHID)
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.
Study Overview
Status
Recruiting
Conditions
Intervention / Treatment
Detailed 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.
Study Type
Interventional
Enrollment (Estimated)
20
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Irina Rifkind, RN, MSN
- Phone Number: 410-502-2043
- Email: irifkin1@jhmi.edu
Study Contact Backup
- Name: Rana Sullivan, RN, BSN
- Phone Number: 410-614-6337
- Email: tomalra@jhmi.edu
Study Locations
-
-
Maryland
-
Baltimore, Maryland, United States, 21228
- Recruiting
- Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
-
Contact:
- Irina Rifkind, RN/MSN
- Phone Number: 410-502-2043
- Email: irifkin1@jhmi.edu
-
Principal Investigator:
- Mark Markowski, MD/PhD
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 120 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
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 ≥ 40 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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Olaparib
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 that have had prior treatment with at least one immune checkpoint inhibitor or anti-VEGF therapy with measureable disease on CT imaging according to RECIST 1.1 criteria.
Participants will be initially treated with olaparib 150mg by mouth twice daily for one month.
After one month of therapy, the dose will be increased to 300mg by mouth twice daily provided there are no grade 3 or greater adverse events experienced.
Reassessment will occur at least monthly for toxicity.
Radiological scans will be performed every 3 months to assess disease response.
Treatment will be continued until clinical and/or radiographic progression according to RECIST 1.1 criteria or unmanageable toxicity requiring cessation.
|
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.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Objective Response or Stable Disease to Olaparib Therapy at Six Months
Time Frame: 6 months post-intervention
|
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.
|
6 months post-intervention
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety of Olaparib Therapy As Determined by the Number of Adverse Events
Time Frame: 2 years
|
Number of Adverse Events, Grade 3 or higher as defined by Common Terminology Criteria for Adverse Events (CTCAE) v5.0
|
2 years
|
Median Progression-Free Survival to Olaparib Therapy
Time Frame: 2 years
|
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.
|
2 years
|
Rate of Objective Response to Olaparib Therapy
Time Frame: 2 years
|
Number of participants with best overall response (complete response (CR) or partial response (PR)) at anytime on study.
|
2 years
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Reversion Mutations in Circulating Tumor DNA (ctDNA) at Clinical Progression
Time Frame: 2 years
|
Number of incidences of reversion mutations in circulating tumor DNA (ctDNA) at time of clinical progression.
|
2 years
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Principal Investigator: Mark C Markowski, MD, Ph.D, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
June 3, 2019
Primary Completion (Estimated)
March 1, 2025
Study Completion (Estimated)
March 1, 2026
Study Registration Dates
First Submitted
December 21, 2018
First Submitted That Met QC Criteria
December 21, 2018
First Posted (Actual)
December 26, 2018
Study Record Updates
Last Update Posted (Estimated)
March 5, 2024
Last Update Submitted That Met QC Criteria
March 4, 2024
Last Verified
March 1, 2024
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Urologic Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Kidney Diseases
- Urologic Diseases
- Adenocarcinoma
- Neoplasms, Glandular and Epithelial
- Female Urogenital Diseases
- Female Urogenital Diseases and Pregnancy Complications
- Urogenital Diseases
- Male Urogenital Diseases
- Kidney Neoplasms
- Carcinoma, Renal Cell
- Carcinoma
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Poly(ADP-ribose) Polymerase Inhibitors
- Olaparib
Other Study ID Numbers
- J18166
- IRB00197147 (Other Identifier: JHM IRB)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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