Last updated: January 18, 2024
Sponsor: Dana-Farber Cancer Institute
Overall Status: Trial Not Available
Phase
2
Condition
Melanoma
Skin Cancer
Treatment
Olaparib
Clinical Study ID
NCT05482074
22-294
Ages > 18 All Genders
Study Summary
Eligibility Criteria
Inclusion
Inclusion Criteria:
- Subjects must have histologically or cytologically confirmed diagnosis of primary orrecurrent metastatic melanoma including cutaneous, mucosal, or uveal melanoma.
- Participants must have a germline or somatic DNA damage repair mutation or deletion inBRCA1 or BRCA2. The result may have been obtained from one of the following testproviders: OncoPanel, SNaPshot Panel, Myriad Genetics, Invitae, Ambry, Quest, ColourGenomics, IMPACT, Foundation Medicine (tissue or ctDNA based), Guardant, or anotherCLIA approved tissue and/or serum based next generation sequencing-based assay. (Variants of uncertain significance are excluded.)
- Participants must have measurable disease as defined by RECIST 1.1 criteria
- At least one lesion, not previously irradiated, that can be accurately measuredat baseline as ≥ 10 mm in the longest diameter (except lymph nodes which musthave short axis ≥ 15 mm) with computed tomography (CT) or magnetic resonanceimaging (MRI) (or Clinical examination) and which is suitable for accuraterepeated measurements.
- Subjects must have received prior checkpoint inhibitor therapy (defined asanti-CTLA4 or anti-PD-1 or combination anti-CTLA4/anti-PD-1), either formetastatic or unresectable disease or progressed on adjuvant therapy.
- Age ≥18 years. Because no dosing or adverse event data are currently available onthe use of olaparib in participants <18 years of age, children are excluded fromthis study, but will be eligible for future pediatric trials.
- Patients must have a life expectancy ≥ 16 weeks.
- ECOG performance status ≤1(Karnofsky ≥60%, see Appendix A).
- Participants must have adequate organ and 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 109/L
- Platelet count ≥ 100 x 109/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 upper limit of normal unless liver metastases are present inwhich case they must be ≤ 5x ULN
- Patients must have creatinine clearance estimated of ≥51 mL/min using theCockcroft-Gault equation or based on a 24 hour urine test: Estimated creatinineclearance = (140-age [years]) x weight (kg) (x F)a / serum creatinine (mg/dL) x 72 (where F=0.85 for females and F=1 for males).
- Participants must have the ability to swallow pills.
- Participants with a prior or concurrent malignancy whose natural history or treatmentdoes not have the potential to interfere with the safety or efficacy assessment of theinvestigational regimen are eligible for this trial.
- The effects of olaparib on the developing human fetus are unknown. For this reason andbecause similar agents are known to be teratogenic, women of child-bearing potentialand men must agree to use adequate contraception (hormonal or barrier method of birthcontrol; abstinence) prior to study entry and for the duration of study participation.Should a woman become pregnant or suspect she is pregnant while she or her partner isparticipating in this study, she should inform her treating physician immediately. Menmust use a condom during treatment and for 3 months after the last dose of olaparibwhen having sexual intercourse with a pregnant woman or with a woman of childbearingpotential. Female partners of male patients should also use a highly effective form ofcontraception if they are of childbearing potential.
- 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 hormonaltreatments
- Luteinizing hormone (LH) and Follicle stimulating hormone (FSH) levels in thepost-menopausal range for women under 50
- 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)
- Measurable disease as defined by RECIST 1.1 criteria -- At least one lesion, that can be accurately measured at baseline as ≥ 10 mm in thelongest diameter (except lymph nodes which must have short axis ≥ 15 mm) with computedtomography (CT) or magnetic resonance imaging (MRI) (or Clinical examination) andwhich is suitable for accurate repeated measurements.
- Ability to understand and the willingness to sign a written informed consent document.
Exclusion
Exclusion Criteria:
- Participants who have had chemotherapy or radiotherapy (except for palliative reasons)for melanoma within 3 weeks prior to entering the study.
- Participants who have not recovered from adverse events due to prior anti-cancertherapy (i.e., have residual toxicities CTCAE > Grade 2) with the exception ofalopecia.
- Participants who are receiving any other investigational agents.
- Other malignancy unless curatively treated with no evidence of disease for ≥5 yearsexcept: adequately treated non-melanoma skin cancer, curatively treated in situ cancerof 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 more than three yearsprior to registration, and that the patient remains free of recurrent or metastaticdisease
- Patients with myelodysplastic syndrome/acute myeloid leukemia or with featuressuggestive of MDS/AML.
- Patients with symptomatic uncontrolled brain metastases. A scan to confirm the absenceof brain metastases is not required. The patient can receive a stable dose ofcorticosteroids before and during the study as long as these were started at least 4weeks prior to treatment.
- Patients with spinal cord compression unless considered to have received definitivetreatment for this and evidence of clinically stable disease for 28 days.
- Patients with a known hypersensitivity to olaparib or any of the excipients of theproduct.
- 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 washoutperiod prior to starting olaparib is 2 weeks. Because the lists of these agents areconstantly changing, it is important to regularly consult a frequently-updated medicalreference. As part of the enrollment/informed consent procedures, the participant willbe counseled on the risk of interactions with other agents, and what to do if newmedications need to be prescribed or if the participant is considering a newover-the-counter medicine or herbal product.
- Concomitant use of known strong (e.g. phenobarbital, enzalutamide, 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 enzalutamide or phenobarbital and 3weeks for other agents.
- Any previous treatment with a PARP inhibitor, including olaparib.
- Resting ECG indicating uncontrolled, potentially reversible cardiac conditions, asjudged by the investigator (e.g., unstable ischemia, uncontrolled symptomaticarrhythmia, congestive heart failure, QTcF prolongation >500 ms, electrolytedisturbances, etc.), or patients with congenital long QT syndrome.
- Patients considered a poor medical risk due to a serious, uncontrolled medicaldisorder, non-malignant systemic disease or active, uncontrolled infection. Examplesinclude, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3months) myocardial infarction, uncontrolled major seizure disorder, unstable spinalcord compression, superior vena cava syndrome, extensive interstitial bilateral lungdisease on High Resolution Computed Tomography (HRCT) scan or any psychiatric disorderthat prohibits obtaining informed consent.
- Participants with psychiatric illness/social situations that would limit compliancewith study requirements.
- Pregnant women are excluded from this study because olaparib is an agent with thepotential for teratogenic or abortifacient effects. Because there is an unknown butpotential risk for adverse events in nursing infants secondary to treatment of themother with olaparib breastfeeding should be discontinued if the mother is treatedwith olaparib.
- Major surgery within 2 weeks of starting study treatment and patients must haverecovered from any effects of any major surgery.
- Previous allogeneic bone marrow transplant or double umbilical cord bloodtransplantation (dUCBT).
- Patients unable to swallow orally administered medication and patients withgastrointestinal disorders likely to interfere with absorption of the studymedication.
- Known HIV or AIDS-related illness.
- Patients with known active hepatitis (i.e. Hepatitis B or C).
- Active hepatitis B virus (HBV) is defined by a known positive HBV surface antigen (HBsAg) result. Patients with a past or resolved HBV infection (defined as thepresence of hepatitis B core antibody and absence of HBsAg) are eligible.
- Patients positive for hepatitis C virus (HCV) antibody are eligible only ifpolymerase chain reaction is negative for HCV RNA.
Study Design
Treatment Group(s): 1
Primary Treatment: Olaparib
Phase: 2
Study Start date:
October 04, 2022
Estimated Completion Date:
May 01, 2027
Study Description
Connect with a study center
Brigham and Women's Hospital
Boston, Massachusetts 02115
United StatesSite Not Available
Dana Farber Cancer Institute
Boston, Massachusetts 02115
United StatesActive - Recruiting
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