Olaparib Monotherapy in HRRm or HRD Positive Cancer
- Conditions
- Homologous recombination repair mutation (HRRm) or Homologous recombination deficiency (HRD) positive cancerMedDRA version: 21.1Level: LLTClassification code 10065252Term: Solid tumorSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-003007-19-IT
- Lead Sponsor
- MERCK SHARP & DOHME CORP. UNA SUSSIDIARIA DI MERCK & CO. INC.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 370
1. Participant has a histologically- or cytologically-confirmed advanced (metastatic and/or unresectable) solid tumor (except breast or ovarian cancers whose tumor has a germline or somatic BRCA mutation) that is not eligible for curative treatment and for which standard of care therapy has failed. Participants must have progressed on or be intolerant to standard of care therapies that are known to provide clinical benefit. There is no limit on the number of prior treatment regimens
2. Participant has either centrally-confirmed known or suspected deleterious mutations in at least 1 of the specified 15 genes involved in HRR (ie, BRCA1, BRCA2, ATM, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D, and RAD54L) or centrally-confirmed HRD based on the Lynparza HRR-HRD assay
3. If participants have received prior platinum (cisplatin, carboplatin, oxaliplatin, etc. either as monotherapy or in combination) for advanced (metastatic and/or unresectable) solid tumor, they are eligible to enter the study provided there has been no evidence of disease progression during the platinum chemotherapy
4. Participant has measurable disease per RECIST 1.1 or PCWG-modified RECIST 1.1 as assessed by the local site Investigator/radiology and confirmed by BICR. BICR must confirm the presence of radiologically measureable disease based on RECIST 1.1 or PCWG-modified RECIST 1.1 for the participant to be eligible for the study. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions
5. Participant is able to provide a newly obtained core or excisional biopsy of a tumor lesion or either an archival formalin-fixed paraffin embedded (FFPE) tumor tissue block or slides. A newly obtained biopsy is preferred, but not required if archival tissue is available for analysis
6. Participant has a life expectancy of at least 3 months
7. Participant is Male or Female who is at least 18 years of age at the time of signing the informed consent
8. Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of either 0 or 1, as assessed within 3 days of treatment initiation
9. A male participant must agree to use contraception during the treatment period and for at least 90 days (3 months), corresponding to time needed to eliminate any study intervention(s) (ie, olaparib) plus a spermatogenesis cycle, after the last dose of study intervention and refrain from donating sperm during this period
10. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies:
a) Not a woman of childbearing potential (WOCBP)
OR
b) A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 30 days (1 month) after the last dose of study intervention, corresponding to time needed to eliminate any study intervention(s (ie, olaparib) plus 30 days (a menstruation cycle) for study interventions with risk of genotoxicity
11. The participant (or legally acceptable representative if applicable) provides written informed consent for the study. The participant may also provide consent for FBR. However, the participant may participate in the main study without participating in FBR
12. Participant has adequate organ function
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age r
1Part has a known addtnal malignancy that is progressing o has requir active treatment the last5years
2Part has myldsplastic syndr(MDS)/acutemyeloidleukemia(AML)o with features sugges of MDS/AML
3Part has persis toxciti(>CTCAEGrade2)caus by previous cancer therapy,exclud alopecia
4Part has know centralnervoussys(CNS)metastases and/o carcin meningitis
5Part has an active infection requiring systemic ther
6Part has a histoy o current evidence of any condition(cytopenia,transfusiondependent anemia,o thrombcytpenia),therapy,o laboatoy abnom that might confound results stu,interfere with part’s invlvment fo full durtin of stu,o is not best interest of part to be involved,in opinion of treating Invstigto
7Part receiv colonystimul factos(granulocyte colonystimul facto[GCSF],granlcyte macrphge colnstimul facto[GMCSF]o recmbnant erytropietin)within28ds prio to first dose of stu intervention
8Part is consider a poo medical risk due to a serious, uncontrolled medical disoder,nonmalignant syst disease o active, uncontrolled infection. Examples include, but are not limited to,uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled majo seizure disoder,unstable spinal cod compression, superio vena cava syndr,extensive interstitial bilateral lung disease on HighResolCompTomography(HRCT)scan o any psychiatric disoder that prohibits obtaining infomed consent
9Part has a known psychiatric o subs abuse disoder that would interfere with cooperation with the requirements of the stu
10Part has a known histoy of human immunodeficiency virus(HIV)infection.Testing fo HIV at screening is only required if mandated by local health authoity.
11Part has known active hepatitis(Hepatitis BoC)a)Active hepatitisBvirus(HBV)is defined by a known positive HBV surface antigen (HBsAg) result. Parts with a past o resolvedHBVinfection(defin as the presence of hepatitis B coe antibody and absence of HBsAg)are eligibleb)Parts positive fo hepatitisCvirus(HCV)antib are eligible only if polymerase chain reaction is negative fo HCV RNA
12Part is unable to swallow oally administered medication o has a gastrointestinal disoder affecting absoption(gastrectomy,partial bowel obstruction,malabsoption)
13Part has received prio therapy with olaparib o with any otherPARPinhibito.
14Part has a known hypersensitivity to the components o excipients in olaparib
15Part is currently receiving either strong (eg, itraconazole, telithromycin, clarithromycin, protease inhibitos boosted with ritonavir o cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) o moderate(ciprofloxacin,erythromycin,diltiazem,fluconazole,verapamil)inhibitos of cytP450(CYP)3A4that cannot be discont fo the duration of the stu.The requir washout period prio to start olaparib is2weeks
16Part is currently receirv either strong(phenobarbital,enzalutamide,phenytoin,rifampicin,rifabutin, rifapentine,carbamazepine,nevirapine andStJohn’sWot)omoderate(bosentan,efavirenz,modafinil)inducers ofCYP3A4that cannot be discontin fo durat of stu.Requir washout period prio to start olaparib is5weeks phenobarbital and3weeks otheragents
17Part has receiv previous allog bonemarrow transplant o double umbilical cod transplantation(dUCBT)
18Part has received a whole blood transfusion in the last120ds prio entry the stu.Pack red blood cels and platelet transfusions are acceptable if not perfom within28ds of the first dose of stu intervention
19Part is currently enrolled in and receiv stu the
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method