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SNCTP000001989 | NCT02787005 | BASEC2016-00662

Phase-2-Studie zu Pembrolizumab bei Patienten mit metastasiertem kastrationsresistentem Prostatakrebs (mCRPC).

Data source: BASEC (Imported from 03.07.2020), WHO (Imported from 05.07.2020)
Changed: 16.06.2020
Disease category: Prostate Cancer

Brief description of trial (Data source: BASEC)

Bei der Kontrolle von Tumoren spielt das Immunsystem eine wichtige Rolle. Pembrolizumab ist ein Antikörper, der die Täuschung des Immunsystems durch den Tumor unterbindet und so die körpereigene Bekämpfung über das PD-L1 Merkmal aktiviert.
Diese klinische Studie soll die Wirkung von Pembrolizumab bei Patienten mit fortgeschrittenem Prostatakrebs untersuchen.
Das Ziel dieser Studie besteht darin, das Ansprechen, die Verträglichkeit und Sicherheit von Pembrolizumab für 5 Kohorten (Behandlungsarme) zu prüfen. Es wird untersucht, ob der PD-L1 Status einen Einfluss auf die Wirksamkeit von Pembrolizumab hat.
Es werden ca. 370 Patienten in eine der 5 Kohorten eingeschlossen, basierend auf die vorangehende Behandlung, dem Status des PD-L1 und des Krebses anhand von bildgebenden Verfahren.
In dieser Studie werden die Patienten alle 3 Wochen mit Pembrolizumab behandelt für eine Dauer von 35 Behandlungen.
Im Rahmen der Studientermine wird eine körperliche Untersuchung mit Messung von Blutdruck, Herzfrequenz, Temperatur, Atemfrequenz und Körpergewicht durchgeführt. Darüber hinaus wird ein Elektrokardiogramm (EKG) aufgezeichnet, sowie bildgebende Untersuchungen des Tumors anhand von Computer- oder Positronen Emissions Tomographien (CT/PET). Ausserdem werden Blut- und Urinproben gesammelt. Falls bei den Patienten die CT-, MRT- oder PET-Untersuchung eine Verschlechterung ihres Krankheitsbildes aufzeigt, werden sie dazu aufgefordert, mindestens 4 Wochen später eine erneute radiologische Untersuchung durchzuführen.
Die Teilnahme an der Studie dauert ca. 2 Jahre.

Health conditions investigated (Data source: BASEC)

Es werden Patienten untersucht, die metastasierten Prostatakrebs im fortgeschrittenen Stadium aufweisen.

Health conditions (Data source: WHO)

Metastatic Castration-resistant Prostate Cancer

Rare disease (Data source: BASEC)

No

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

Die in diese Studie aufgenommenen Patienten werden einer der 5 Kohorten zugeteilt, basierend auf der vorangehenden Behandlung, dem PD-L1 Status sowie der Messbarkeit des Krebses anhand von bildgebenden Verfahren. Patienten, die vorgängig mit einer Docetaxel-basierten Chemotherapie behandelt wurden, erhalten in den Kohoren 1 bis 3 eine Pembrolizumab-Monotherapie. Chemotherapie-naive Teilnehmer mit mCRPC, die entweder nicht auf Enzalutamid angesprochen haben oder bei denen Hinweise auf ein Therapieversagen vorliegen, erhalten zusätzlich zu ihrer laufenden Enzalutamid-Behandlung eine Therapie mit Pembrolizumab.

Interventions (Data source: WHO)

Drug: Enzalutamide;Biological: Pembrolizumab

Criteria for participation in trial (Data source: BASEC)

1. Patienten, die einen histologisch oder zytologisch bestätigten metastasierten Prostatakrebs aufweisen.
2. Patient muss entweder einen mittels CT oder MRT nachgewiesenen Prostatakrebs aufweisen, welcher die in RECIST 1.1 definierten Kriterien erfüllt (Kohorten 1, 2, 4) ODER Metastasen in den Knochen aufweisen und keinen gemäss RECIST 1.1 definierten Tumor haben (Kohorten 3 und 5).
3. Patienten mit einer fortschreitenden Erkrankung Verschlechterung innerhalb der letzten 6 Monate vor der Screening Visite.

Exclusion criteria (Data source: BASEC)

1. Bekannte aktive Metastasen im Zentralnervensystem und/oder karzinomatöse Meningitis. Patienten mit vorbehandelten Hirnmetastasen sind für die Teilnahme geeignet, wenn sie mindestens vier Wochen vor der ersten Gabe des Studienmedikaments stabile Hirnmetastasen aufweisen.
2. Patienten haben bereits an einer anderen Studie zu Pembrolizumab teilgenommen oder sind bereits früher mit einer Therapie, die ähnlich wie Pembrolizumab wirkt, behandelt worden oder sie haben auf eine Behandlung mit einem monoklonalen Antikörper ungünstig reagiert.
3. Patienten haben eine aktive Autoimmunkrankheit (eine Krankheit, die auftritt, wenn das Gewebe fälschlicherweise vom eigenen Immunsystem angegriffen wird), die in den vergangenen zwei Jahren eine systemische Behandlung (d. h. mit einem Medikament, das oral oder über eine Vene verabreicht wird) erforderlich machte.

Inclusion/Exclusion Criteria (Data source: WHO)


Inclusion Criteria:

- Has histologically- or cytologically-confirmed adenocarcinoma of the prostate without
small cell histology. Disease must be either metastatic or locally confined inoperable
disease that cannot be treated with definitive intent (no chance for a curative
intervention).

- Has supplied tumor tissue from a newly obtained biopsy or a biopsy obtained =12 months
prior to study start and an archival specimen, if available, from a site not
previously irradiated. Participants in Cohorts 1, 2, and 4 with visceral/measurable
lesions must provide a newly obtained biopsy performed after the last line of systemic
therapy or a biopsy obtained =12 months prior to study start and an archival specimen,
if available. Participants in Cohorts 3 and 5 must at least provide an archival
specimen.

For Cohorts 1, 2, and 3 only:

- Has been treated with:

- At least 1 targeted endocrine therapy (defined as second generation antiandrogen
therapies that include but are not limited to abiraterone acetate with prednisone,
enzalutamide, and next generation targeted agents such as ARN-509).

- At least 1 regimen/line of chemotherapy that contained docetaxel.

- No more than 2 chemotherapy regimens.

- No more than 3 regimens/lines of the aforementioned treatments (having
failed/progressed on chemotherapy and targeted endocrine therapy).

For Cohorts 4 and 5 only:

- Failing or showing early signs of failure on current pre-chemotherapy enzalutamide
treatment as defined by Prostate Cancer Working Group 3 PCWG3 guidelines. Participants
can have failed prior abiraterone treatment before current enzalutamide treatment.
Participants must have had a clinically meaningful response to enzalutamide treatment.
Enzalutamide must have been initiated no less than 4 weeks prior to the first dose of
trial treatment and be continued throughout the study.

For All Cohorts:

- Has documented prostate cancer progression within 6 months prior to screening, as
determined by the Investigator, by means of one of the following: 1) PSA progression
as defined by a minimum of 3 rising PSA levels with an interval of =1 week between
each assessment where the PSA value at screening should be =2 ng/mL, OR, 2)
Radiographic disease progression in soft tissue or bone with or without PSA
progression

- Has ongoing androgen deprivation with total serum testosterone <50 ng/dL (<2.0 nM).

- Participants receiving bone resorptive therapy (including but not limited to
bisphosphonate or Receptor activator of nuclear factor kappa-B ligand [RANK-L
inhibitor]) must have been on stable doses for =4 weeks prior to first dose of study
drug.

- Has a performance status of 0, 1 or 2 on the Eastern Cooperative Oncology Group (ECOG)
Performance Scale

- Males of reproductive potential must agree to use an adequate method of contraception,
starting with the first dose of study drug through 120 days after the last dose of
study drug.

- Demonstrates adequate organ function.

Exclusion Criteria:

For All Cohorts:

- Is currently participating and receiving study therapy or has participated in a study
of an investigational agent and received study therapy or used an investigation device
within 4 weeks of the first dose of study drug.

- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
other form of immunosuppressive therapy within 7 days prior to the first dose of study
drug.

- Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to the
first dose of study drug or who has not recovered (i.e., = Grade 1 or at Baseline)
from AEs due to mAbs administered more than 4 weeks earlier.

- Has had prior chemotherapy, targeted small molecule therapy, or external beam
radiation therapy within 4 weeks prior to the first dose of study drug or who has not
recovered (i.e., = Grade 1 or at Baseline) from AEs due to a previously administered
agent.

- Has a known additional malignancy that has had progression or has required active
treatment in the last 3 years. Exceptions include basal cell carcinoma of the skin and
squamous cell carcinoma of the skin that has undergone potentially curative therapy.

- Has known active central nervous system (CNS) metastases and/or carcinomatous
meningitis.

- Has an active autoimmune disease that has required systemic treatment in past 2 years
(i.e., with use of disease modifying agents, corticosteroids or immunosuppressive
drugs).

- Has evidence of interstitial lung disease and/or a history of (non-infectious)
pneumonitis that required steroids, or current pneumonitis.

- Has an active infection requiring systemic therapy.

- Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.

- Has previously participated in any other pembrolizumab (MK-3475) trial, or received
prior therapy with an anti-programmed cell death 1 (anti-PD-1, anti-PD ligand 1
[anti-PD-L1], and anti-PD-L2 [including ipilimumab or any other antibody or drug
specifically targeting T-cell co-stimulation or checkpoint pathways]).

- Has a known history of Human Immunodeficiency Virus (HIV).

- Has known active Hepatitis B or Hepatitis C.

- Has received a live vaccine within 30 days of planned start of study drug.

For Cohorts 4 and 5 only:

- Has received prior chemotherapy (e.g., docetaxel) for mCPRC.

- Has any condition (cardiac, neurologic, absorption) other than clinically failing or
showing early signs of failure on enzalutamide treatment that would require imminent
discontinuation of enzalutamide treatment.

Further information on the trial in WHO primary registry

https://clinicaltrials.gov/show/NCT02787005

Further information on the trial from WHO database (ICTRP)

http://apps.who.int/trialsearch/Trial2.aspx?TrialID=NCT02787005

Further information on trial

Date trial registered

26.05.2016

Incorporation of the first participant

01.07.2016

Recruitment status

Active, not recruiting

Academic title (Data source: WHO)

Phase II Trial of Pembrolizumab (MK-3475) in Subjects With Metastatic Castration-Resistant Prostate Cancer (mCRPC) (KEYNOTE-199)

Type of trial (Data source: WHO)

Interventional

Design of the trial (Data source: WHO)

Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).

Phase (Data source: WHO)

Phase 2

Primary end point (Data source: WHO)

Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 assessed by central imaging vendor (Cohorts 1 and 2 combined, Cohort 1, Cohort 2 and Cohort 4)

Secundary end point (Data source: WHO)

Disease Control Rate (DCR) (Cohorts 1 and 2 combined, Cohorts 1, 2, and 3 combined, Cohorts 4 and 5 combined, and by each cohort);Prostate-specific Antigen (PSA) response rate (Cohorts 1 and 2 combined, Cohorts 1, 2, and 3 combined, Cohorts 4 and 5 combined, and by each cohort);Percentage of participants who experience an adverse event (AE) (All cohorts combined and by each cohort);Percentage of participants who discontinue study drug due to an AE (All cohorts combined and by each cohort)

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)

Basel, Chur, Luzern, St. Gallen

Countries (Data source: WHO)

Australia, Canada, Estonia, Finland, France, Germany, Hong Kong, Ireland, Israel, Italy, Japan, Korea, Netherlands, Poland, Republic of, Spain, Sweden, Switzerland, Taiwan, 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
Merck Sharp & Dohme Corp.

Contact for scientific information (Data source: WHO)

Medical Director
Merck Sharp & Dohme Corp.

Principal Sponsor/Investigator

Principal sponsor (Data source: WHO)

Merck Sharp & Dohme Corp.

Authorisation by the ethics committee (Data source: BASEC)

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

Ethikkommission Ostschweiz (EKOS)

Date of authorisation by the ethics committee

25.07.2016

Further trial identification numbers

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

2016-00662

Secondary ID (Data source: WHO)

2015-003644-40
163366
MK-3475-199
3475-199