Olaparib Therapy in HRRm or HRD Positive Cancer (MK-7339-002)
Résumé de l'étude
The aim of this study is to investigate the safety, efficacy, and tolerability of the study drug Olaparib in the various HRRm subgroups. The entire study is expected to last approximately 4.5 years. Both participants and the study physician are aware of the treatment being applied (it is a so-called "open" study). Each participant receives 300 mg of Olaparib tablets twice daily.
(BASEC)
Intervention étudiée
Approximately 370 patients are expected to participate in this study worldwide.
After a thorough eligibility assessment, collection of medical history, and detailed explanation, the participant will be included in the study. Thereafter, they will take the study drug Olaparib twice daily (600 mg per day) and will attend visits at the study center as agreed with the study physician (approximately every 4 weeks during the intake of the medication).
Treatment with Olaparib continues as long as the cancer does not worsen and there are no serious side effects.
During the study visits, various measures and examinations may take place: discussion of well-being and current medication, imaging procedures (CT, MRI scans or bone scans), electrocardiogram (ECG), samples of blood, urine, or tissue, questionnaires, as well as examination of vital functions (pulse, blood pressure, etc.).
Follow-Up Phase:
After treatment with Olaparib, the participant enters the follow-up phase. For this, they will attend visits at the study center approximately every 8-12 weeks. Visits at the study center only occur if the patient had to discontinue the study due to side effects.
If the cancer worsens (confirmed by imaging) or the patient receives another cancer therapy, they will be contacted by the study team approximately every 12 weeks or more frequently to inquire about their health status.
(BASEC)
Maladie en cours d'investigation
This study examines participants with previously treated, advanced cancer who tested positive for HRRm or HRD (HRRm stands for "Homologous Recombination Repair Mutation", HRD stands for "Homologous Recombination Deficiency"). Various genetic mutations play a role, meaning it concerns specific changes in the genetic information in human cells. In this study, the mechanism of action of the study drug is investigated in participants with different alterations. PARP proteins are responsible for correcting DNA damage during cell division. Such DNA damage primarily occurs in cancer cells. The study drug, Olaparib, inhibits PARP proteins. When these proteins are inhibited, it leads to the death of cancer cells, as certain DNA damages can no longer be repaired, thus the cancer cell is the primary target of this study medication.
(BASEC)
• Participant suffers from advanced solid cancer for which one or more standard therapies have failed. • Participant's tumor is HRRm or HRD positive. • Participant is at least 18 years old and has a life expectancy of at least 3 months. (BASEC)
Critères d'exclusion
• Metastases in the central nervous system and/or involvement of the meninges by metastatic cancer cells • Additional malignant disease that is progressing or required active treatment in the last 5 years (with few exceptions) • Myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) (BASEC)
Lieu de l’étude
Bellinzona, Genève, Zurich
(BASEC)
Sponsor
MSD Merck Sharp & Dohme AG, Luzern
(BASEC)
Contact pour plus d'informations sur l'étude
Personne de contact en Suisse
Klaudia Georgi
+41 58 618 33 88
klaudia.georgi@cluttermsd.comMSD Merck Sharp & Dohme AG, Luzern
(BASEC)
Informations générales
Merck Sharp & Dohme LLC
(ICTRP)
Informations scientifiques
Merck Sharp & Dohme LLC
(ICTRP)
Nom du comité d'éthique approbateur (pour les études multicentriques, uniquement le comité principal)
Commission cantonale de Zurich
(BASEC)
Date d'approbation du comité d'éthique
19.12.2018
(BASEC)
Identifiant de l'essai ICTRP
NCT03742895 (ICTRP)
Titre officiel (approuvé par le comité d'éthique)
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 (BASEC)
Titre académique
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 (ICTRP)
Titre public
Efficacy and Safety of Olaparib (MK-7339) in Participants With Previously Treated, Homologous Recombination Repair Mutation (HRRm) or Homologous Recombination Deficiency (HRD) Positive Advanced Cancer (MK-7339-002 / LYNK-002) (ICTRP)
Maladie en cours d'investigation
Advanced Solid Neoplasms (ICTRP)
Intervention étudiée
Drug: Olaparib (ICTRP)
Type d'essai
Interventional (ICTRP)
Plan de l'étude
Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)
Critères d'inclusion/exclusion
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. (ICTRP)
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Critères d'évaluation principaux et secondaires
Objective Response Rate (ORR) (ICTRP)
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 Cancer (ICTRP)
Date d'enregistrement
14.11.2018 (ICTRP)
Inclusion du premier participant
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Sponsors secondaires
AstraZeneca (ICTRP)
Contacts supplémentaires
Medical Director, Merck Sharp & Dohme LLC (ICTRP)
ID secondaires
MK-7339-002, LYNK-002, 194694, 2022-500797-34-00, U1111-1278-1505, 2018-003007-19, 7339-002 (ICTRP)
Résultats-Données individuelles des participants
non disponible
Informations complémentaires sur l'essai
https://clinicaltrials.gov/study/NCT03742895 (ICTRP)
Résultats de l'essai
Résumé des résultats
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Lien vers les résultats dans le registre primaire
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