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SNCTP000003157 | NCT03742895 | BASEC2018-01891

Olaparib-Therapie bei HRRm- oder HRD-positivem Krebs (MK-7339-002)

Data source: BASEC (Imported from 28.03.2024), WHO (Imported from 20.03.2024)
Changed: Feb 27, 2024, 1:00 AM
Disease category: Other Cancer

Brief description of trial (Data source: BASEC)

Ziel dieser Studie ist es, die Sicherheit, Wirksamkeit und Verträglichkeit des Studienmedikaments Olaparib in den verschiedenen HRRm Sub-gruppen zu untersuchen. Die gesamte Studie dauert voraussichtlich ca. 4.5 Jahre. Sowohl Teilnehmer als auch Studienarzt wissen über die angewendete Therapie Bescheid (es ist eine sogenannte „offene“ Studie). Jeder Teilnehmer bekommt 300mg Olaparib Tabletten zweimal täglich.

Health conditions investigated(Data source: BASEC)

Es werden Studienteilnehmer mit bereits behandelter, fortgeschrittener Krebserkrankung untersucht, welche positiv auf HRRm oder HRD getested wurden (HRRm steht dabei für „Homologous Recombination Repair Mutation“, HRD für „Homologous Recombination Deficiency“). Hierbei spielen verschiedene Genmutationen eine Rolle, d.h. es geht um spezifische Veränderungen der Erbinformation in den menschlichen Zellen. In dieser Studie wird die Wirkungsweise des Studienmedikaments in Studienteilnehmer mit den unterschiedlichen Veränderungen untersucht. PARP Proteine sind zuständig, um DNA-Schäden während der Zellteilung zu korrigieren. Solche DNA-Schäden treten hauptsächlich in Krebszellen auf. Das Studienmedikament, Olaparib, hemmt die PARP Proteine. Werden diese Proteine gehemmt, führt dies zu einem Absterben der Krebszellen, da gewisse DNA- Schäden nicht mehr repariert werden können und somit ist die Krebszelle das primäre Ziel dieser Studienmedikation.

Health conditions (Data source: WHO)

Advanced Solid Neoplasms

Rare disease (Data source: BASEC)

No

Intervention investigated (e.g. drug, therapy or campaign) (Data source: BASEC)

Bei dieser Studie werden voraussichtlich weltweit rund 370 Patienten teilnehmen.

Nach genauer Eignungsprüfung, Erhebung der Krankengeschichte und ausführlicher Aufklärung wird der Teilnehmer in die Studie eingeschlossen. Danach nimmt er zweimal täglich das Studienmedikament Olaparib zu sich (600 mg pro Tag) und erscheint wie mit dem Studienarzt vereinbart zu Visiten am Studienzentrum (ca. alle 4 Wochen während der Einnahme des Medikaments).

Die Behandlung mit Olaparib dauert an, so lange sich die Krebserkrankung nicht verschlechtert und es zu keinen schwerwiegenden Nebenwirkungen kommt.

Im Rahmen der Studientermine können unterschiedliche Massnahmen und Untersuchungen erfolgen: Besprechung des Befindens und der aktuellen Medikation, bildgebende Verfahren (CT-, MRT-Untersuchungen oder Knochenscans), Elektrokardiogramm (EKG), Proben von Blut, Urin, oder Gewebe, Fragebogen sowie Untersuchung der Vitalfunktionen (Puls, Blutdruck, etc.).

Follow-Up-Phase (Nachbeobachtung):
Nach der Behandlung mit Olaparib tritt der Teilnehmer in die Follow-up-Phase über. Hierfür wird er ca. alle 8-12 Wochen zu Visiten am Studienzentrum erscheinen. Die Visiten am Studienzentrum finden nur dann statt, wenn der Patient die Studie wegen Nebenwirkungen beenden musste.
Falls sich die Krebserkrankung verschlechtert (bestätigt in der Bildgebung) oder der Patient eine andere Krebstherapie erhält, wird er ungefähr alle 12 Wochen oder häufiger vom Studienteam kontaktiert und nach seinem Gesundheitsstatus befragt.

Interventions (Data source: WHO)

Drug: Olaparib

Criteria for participation in trial (Data source: BASEC)

• Teilnehmer leidet an einer fortgeschrittenen, soliden Krebserkrankung, bei welcher eine oder mehrere Standardtherapien erfolglos waren.

• Tumor des Teilnehmers ist HRRm- oder HRD-positiv.

• Teilnehmer ist mindestens 18 Jahre alt und hat eine Lebenserwartung von mindestens 3 Monaten.

Exclusion criteria (Data source: BASEC)

• Metastasen im Zentralen Nervensystem und/oder Besiedlung der Hirnhäute mit metastasierenden Krebszellen

• Zusätzliche bösartige Erkrankung, die fortschreitet oder in den letzten 5 Jahren eine aktive Behandlung erforderte (mit wenigen Ausnahmen)

• Myelodysplastisches Syndrom (MDS) oder Akute Myeloide Leukämie (AML)

Inclusion/Exclusion Criteria (Data source: WHO)

Gender: All
Maximum age: N/A
Minimum age: 18 Years

Inclusion Criteria:

- For all participants:

- 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.

- 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.

- Has a life expectancy of at least 3 months.

- Has an Eastern Cooperative Oncology Group (ECOG) performance status of either 0 or 1,
as assessed within 7 days of treatment initiation.

- Male participants must agree to use contraception during the treatment period and for
at least 95 days (3 months and 5 days) after the last dose of study treatment and
refrain from donating sperm during this period.

- A female participant is eligible to participate if she is not pregnant or
breastfeeding, and at least one of the following conditions applies:

1. Is not a woman of childbearing potential (WOCBP).

2. Is a WOCBP and using a contraceptive method that is highly effective with low
user dependency, or be abstinent from heterosexual intercourse as their preferred
and usual lifestyle (abstinent on a long term and persistent basis), during the
intervention period and for at least 180 days after the last dose of study
intervention, AND agrees not to donate eggs (ova, oocytes) to others or
freeze/store for her own use for the purpose of reproduction during this period.
Abstains from breastfeeding during the study intervention period and for at least
30 days after the last dose of study intervention.

- Has adequate organ function.

- For participants who have non-breast or -ovarian cancers that are breast cancer
susceptibility gene 1/2 (BRCA1/2) mutated (BRCAm), or who have cancers that are
BRCA1/2 non-mutated and homologous recombination repair nonmutated:

- Has a histologically- or cytologically-confirmed advanced (metastatic and/or
unresectable) solid tumor (except ovarian cancer whose tumor has a germline or somatic
BRCA mutation and breast cancer whose tumor has a germline 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.

- Has either centrally-confirmed known or suspected deleterious mutations in at least 1
of the genes involved in HRR or centrally-confirmed HRD.

- For participants receiving prior platinum (cisplatin, carboplatin, or oxaliplatin
either as monotherapy or in combination) for advanced (metastatic and/or unresectable)
solid tumor, have no evidence of disease progression during the platinum chemotherapy
or =4 weeks of completing the platinum-containing regimen.

- For participants who have somatic BRCAm breast cancer:

- Has histologically- or cytologically-confirmed breast cancer with evidence of
metastatic disease.

- Has a known or suspected deleterious mutation in breast cancer susceptibility gene
(BRCA) 1 or BRCA2 and does not harbor a germline BRCA1 or BRCA2 mutation - testing can
be done centrally or locally. Blood and tissue samples must be provided by all
participants.

- Has received treatment with an anthracycline unless contraindicated and a taxane in
either the neoadjuvant/adjuvant or metastatic setting.

- Participants with estrogen and/or progesterone receptor-positive disease must have
received and progressed on at least one endocrine therapy (adjuvant or metastatic), or
have disease that the treating physician believes to be inappropriate for endocrine
therapy.

Exclusion Criteria:

- Has a known additional malignancy that is progressing or has required active treatment
in the last 5 years. Note: Participants with basal cell carcinoma of the skin,
squamous cell carcinoma of the skin, ductal carcinoma in situ, or cervical carcinoma
in situ that has undergone potentially curative therapy are not excluded.

- Has myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or with features
suggestive of MDS/AML.

- Has known central nervous system (CNS) metastases and/or carcinomatous meningitis.
Note: Participants with previously treated brain metastases may participate if
radiologically stable, clinically stable, and without requirement for steroid
treatment for at least 14 days prior to the first dose of study treatment.

- Has received colony-stimulating factors (e.g., granulocyte colony-stimulating factor
[G-CSF], granulocyte-macrophage colony-stimulating factor [GM-CSF] or recombinant
erythropoietin) within 28 days prior to the first dose of study treatment.

- Has a known history of human immunodeficiency virus (HIV) infection.

- Has known active hepatitis infection (i.e., Hepatitis B or C).

- Is unable to swallow orally administered medication or has a gastrointestinal disorder
affecting absorption (e.g., gastrectomy, partial bowel obstruction, malabsorption).

- Has received prior therapy with olaparib or with any other polyadenosine 5'
diphosphoribose (poly[ADP ribose]) polymerization (PARP) inhibitor.

- Has a known hypersensitivity to the components or excipients in olaparib.

- Has received previous allogenic bone-marrow transplant or double umbilical cord
transplantation (dUCBT).

- Has received a whole blood transfusion in the last 120 days prior to entry to the
study. Packed red blood cells and platelet transfusions are acceptable if not
performed within 28 days of the first dose of study treatment.

- Has received any anti-neoplastic systemic chemotherapy or biological therapy, targeted
therapy, or an anticancer hormonal therapy within 3 weeks prior to the first dose of
study intervention.

- Has a primary cancer of unknown origin.

- Has received prior radiotherapy within 2 weeks of start of study intervention.
Participants must have recovered from all radiation-related toxicities, not require
corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted
for palliative radiation (=2 weeks of radiotherapy) to non-CNS disease.

Further information on the trial in WHO primary registry

https://clinicaltrials.gov/ct2/show/NCT03742895

Further information on the trial from WHO database (ICTRP)

https://trialsearch.who.int/Trial2.aspx?TrialID=NCT03742895
Further information on trial

Date trial registered

Nov 14, 2018

Recruitment status

Recruiting

Academic title (Data source: WHO)

A Phase 2 Study of Olaparib Monotherapy in Participants With Previously Treated, Homologous Recombination Repair Mutation (HRRm) or Homologous Recombination Deficiency (HRD) Positive Advanced Cancer

Type of trial (Data source: WHO)

Interventional

Design of the trial (Data source: WHO)

Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).

Phase (Data source: WHO)

Phase 2

Primary end point (Data source: WHO)

Objective Response Rate (ORR)

Secundary end point (Data source: WHO)

Duration of Response (DOR);Overall Survival (OS);Progression Free Survival (PFS);Number of Participants Experiencing an Adverse Event (AE);Number of Participants Discontinuing Study Treatment due to an Adverse Event (AE);Objective Response Rate (ORR) in Participants with HRRm or HRD Positive Cancer;Time to Earliest Progression by Cancer Antigen-125 (CA-125);Prostate-specific Antigen (PSA) Response Rate in Participants with Prostate Cancer;Progression-Free Survival After Next-Line Treatment in Participants with sBRCAm Breast Cance

Contact information (Data source: WHO)

Please refer to primary and secondary sponsors

Trial results (Data source: WHO)

Results summary

no information available yet

Link to the results in the primary register

no information available yet

Information on the availability of individual participant data

no information available yet

Trial sites

Trial sites in Switzerland (Data source: BASEC)

Bellinzona, Geneva, Zurich

Countries (Data source: WHO)

Argentina, Australia, Canada, Colombia, Denmark, France, Guatemala, Ireland, Israel, Italy, Japan, Korea, Mexico, Peru, Republic of, Romania, Russian Federation, Spain, Switzerland, Turkey, United Kingdom, United States

Contact for further information on the trial

Details of contact in Switzerland (Data source: BASEC)

Klaudia Georgi
+41 58 618 33 88
klaudia.georgi@msd.com

Contact for general information (Data source: WHO)

Medical Director;Toll Free Number
Merck Sharp & Dohme LLC
1-888-577-8839
Trialsites@merck.com

Contact for scientific information (Data source: WHO)

Medical Director;Toll Free Number
Merck Sharp & Dohme LLC
1-888-577-8839
Trialsites@merck.com

Authorisation by the ethics committee (Data source: BASEC)

Name of the authorising ethics committee (for multicentre studies only the lead committee)

Kantonale Ethikkommission Zürich

Date of authorisation by the ethics committee

19.12.2018

Further trial identification numbers

Trial identification number of the ethics committee (BASEC-ID) (Data source: BASEC)

2018-01891

Secondary ID (Data source: WHO)

MK-7339-002
LYNK-002
194694
2018-003007-19
7339-002
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