Clinical Trials Register

Summary
EudraCT Number:	2011-002803-13
Sponsor's Protocol Code Number:	1775-004
National Competent Authority:	Hungary - National Institute of Pharmacy
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2012-06-28
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Hungary - National Institute of Pharmacy

A.2

EudraCT number

2011-002803-13

A.3

Full title of the trial

A Randomized, Phase II Study Evaluating MK-1775 in Combination with Paclitaxel and Carboplatin versus Paclitaxel and Carboplatin Alone in Adult Patients with Platinum Sensitive p53 Mutant Ovarian Cancer

Randomizált, kettes fázisú vizsgálat, mely az MK-1775 és paclitaxel/karboplatin kombinációt elemzi önmagában adott paclitaxel/karboplatinnal szemben, platinaérzékeny p53 mutáns petefészekrákban szenvedő felnőtt betegeknél.

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

MK1775 in Comb. with Paclitaxel&Carboplatin vs Paclitaxel&Carboplatin Alone

MK-1775 és paclitaxel/karboplatin kombinációban alkalmazva , önmagában alkalmazott paclitaxel/karboplatinnal szemben.

A.3.2

Name or abbreviated title of the trial where available

MK1775 in Comb. with Paclitaxel&Carboplatin vs Paclitaxel&Carboplatin Alone

MK1775+paclitaxel/karboplatin komb. alkalmazva,önmagában alkalm. paclitaxel/karboplatinnal szemben

A.4.1

Sponsor's protocol code number

1775-004

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01357161

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
B.5.2	Functional name of contact point	Shelonitda Rose
B.5.3	Address:
B.5.3.1	Street Address	One Merck Drive, P.O. Box 100
B.5.3.2	Town/ city	Whitehouse Station
B.5.3.3	Post code	08889-0100
B.5.3.4	Country	United States
B.5.4	Telephone number	19087402560
B.5.5	Fax number	19087405705
B.5.6	E-mail	shelonitda.rose@merck.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	Regulation (EC) n° 141/2000)
D.3 Description of the IMP
D.3.1	Product name	MK-1775
D.3.2	Product code	MK-1775
D.3.4	Pharmaceutical form	Capsule
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	NA
D.3.9.1	CAS number	955365-80-7
D.3.9.2	Current sponsor code	MK-1775
D.3.9.3	Other descriptive name	MK-1775
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	25
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	Regulation (EC) n° 141/2000
D.3 Description of the IMP
D.3.1	Product name	MK-1775
D.3.2	Product code	MK-1775
D.3.4	Pharmaceutical form	Capsule
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	NA
D.3.9.1	CAS number	955365-80-7
D.3.9.2	Current sponsor code	MK-1775
D.3.9.3	Other descriptive name	MK-1775
D.3.10	Strength
D.3.10.1	Concentration unit	mg/g milligram(s)/gram
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Capsule
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Ovarian, Fallopian Tube, or Peritoneal cancer

Petefészek, petevezeték vagy hashártya daganat.

E.1.1.1

Medical condition in easily understood language

Cancer of the ovaries, Fallopian Tube, or peritoneum

Petefészek, petevezeték vagy hashártya daganat.

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10033130
E.1.2	Term	Ovarian cancer NOS
E.1.2	System Organ Class	100000004864

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

(1) To evaluate the effect of MK-1775 in combination with paclitaxel + carboplatin compared with placebo in combination with paclitaxel + carboplatin on PFS per enhanced RECIST 1.1 in patients with platinum sensitive p53 mutant ovarian cancer. (2) To determine the safety and tolerability of MK-1775 in combination with paclitaxel + carboplatin in patients with platinum sensitive p53 mutant ovarian cancer.

(1)Az MK-1775-tel együtt alkalmazott paclitaxel/karboplatin és a placebóval együtt adott paclitaxel/karboplatin hatásának értékelése a progressziómentes túlélésre, az 1.1 bővített RECIST verziója alapján, platinaérzékeny p53 mutáns petefészekrákban szenvedő betegeknél.(2)A paclitaxel/karboplatinnal együtt alkalmazott MK-1775 biztonságosságának és tolerálhatóságának a vizsgálata platinaérzékeny p53 mutáns petefészekrákban szenvedő betegeknél.

E.2.2

Secondary objectives of the trial

(1) To evaluate the effect of the combination of paclitaxel + carboplatin in combination with MK-1775 versus paclitaxel + carboplatin alone on ORR in patients with platinum sensitive p53 mutant ovarian cancer. (2) To evaluate the effect of the combination of paclitaxel + carboplatin in combination with MK-1775 versus paclitaxel + carboplatin alone on OS in patients with platinum sensitive p53 mutant ovarian cancer. (3) To determine pharmacodynamic changes induced by MK-1775 combined with paclitaxel + carboplatin in surrogate tissue at the 175 and 125 mg dose, should these dose levels be explored. (4) To assess the pharmacokinetic profile of MK-1775 in combination with paclitaxel + carboplatin in patients with platinum sensitive p53 mutant ovarian cancer. (5) To assess the pharmacokinetic profile of paclitaxel in combination with MK-1775 + carboplatin in patients with platinum sensitive p53 mutant ovarian cancer.

(1)MK1775 együtt alkalmazott paclitaxel/karboplatin és az önmagában adott paclitaxel/karboplatin hatásának vizsgálata a kezelésre adott obj. válaszarányra, platinaérzékeny p53 mutáns petefészekrákban szenvedő betegeknél.(2)MK1775 együtt alkm. paclitaxel/karboplatin és az önmagában adott paclitaxel/karboplatin hatásának vizsgálata az általános túlélésre, platinaérzékeny p53 mutáns petefészekrákban szenvedő betegeknél. (3)A paclitaxel/karboplatinnal együtt alkalmazott MK1775 által előidézett farmakodinamikai változások meghatározása a környező szövetben, 175mg-os és 125mg-os adagolás esetén, amennyiben ezek a dózisszintek kerülnek meghatározásra.(4)A paclitaxel/karboplatin kombinációval együtt alkalmazott MK1775 farmakokinetikai profiljának az értékelése platinaérzékeny p53 mutáns petefészekrákban szenvedő betegeknél.(5)Az MK1775/karboplatin kombinációval együtt alk. paclitaxel farmakokinetikai profiljának az értékelése platinaérzékeny p53 mutáns petefészekrákban szenvedő betegeknél.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

(1) Patient must have a histologically confirmed non-low grade, non-borderline (low malignant potential) ovarian, fallopian tube, or primary peritoneal cancer that has progressed after paclitaxel / platinum based therapy.
(2) Patients must have platinum sensitive disease. Progression must have occurred 6 months or more after the completion of the most recent platinum based treatment.
(3) Patient is able to provide a baseline tumor sample. The submitted tumor sample must have tested positive for a loss-of-function p53 mutation (as defined in the assay charter) and the result must be documented by a core lab for the study.
(4) Part 1 - Patient may not have received more than two platinum containing treatment regimens for their cancer. Part 2 - Patient may not have received more than three separate regimens of platinum containing treatment for their cancer.
(5) Any biologic therapy or radiation must have been completed four weeks prior to receiving study therapy. With the exception of alopecia, the patient must have recovered to ≤ Grade 1 from adverse events due to previous agents administered. Biologic maintenance therapy (i.e. bevacizumab) is allowable within this six month period. Any biologic maintenance therapy must have been discontinued 28 days prior to the patient starting study therapy.

(1)A betegnek szövettani vizsgálat által megerősített közepes vagy súlyos, nem borderline típusú (alacsony malignitású potenciál) petefészek, petevezeték, vagy hashártya daganata van, amely progrediált a paclitaxel/karboplatin terápiát követően.
(2)A betegeknek platinaérzékeny daganata van. A progresszió a legutolsó platina alapú kezelés befejezését követően legalább 6 hónappal történt.
(3)A betegnek kezdeti (baseline) tumormintát szükséges adnia. A nyert tumormintának pozitívnak kell lennie p53 funkcióvesztéses mutáció szempontjábol (mint ahogyan meg van határozva a vizsgálat ismertetőjében is), és az eredmény dokumentálva kell legyen a vizsgálatban meghatározott központi laboratórium által.
(4)Első rész: A beteg nem kaphatott kettőnél több, platinát tartalmazó kezelést (paclitaxel/karboplatin) a daganat kezelésére. Második rész: a beteg nem kaphatott háromnál több, különálló, platinát tartalmazó kezelést a daganat kezelésére.
(5)Bármilyen biológiai vagy sugárterápiának be kell fejeződnie legalább négy héttel a vizsgálati terápiát megelőzően. A betegnek ≤ 1 fokozatig gyógyultnak kell lennie a korábban alkalmazott szerek által előidézett nemkívánatos események hatásaiból, a hajhullás kivételével. A biológiai fenntartó terápia (pl. bevacizumab) engedélyezett ezen hat hónapos időszak alatt. Bármilyen biológiai fenntartó kezelést abba kell hagyni 28 nappal a vizsgálati terápia megkezdése előtt.

E.4

Principal exclusion criteria

(1) Patient is currently participating or has participated in a study with an investigational compound or device within 28 days of receiving first dose of study medication.
(2) Patients with active CNS metastases and/or carcinomatous meningitis are excluded. However, patients with CNS metastases who have completed a course of therapy would be eligible for the study provided they are clinically stable for 1 month prior to entry as defined as: (1) no evidence of new or enlarging CNS metastasis (2) off steroids or on a stable dose of steroids for at least 2 weeks.
(3) Patient with a primary central nervous system tumor.
(4) Patient has known hypersensitivity or contraindications to the components of potential study therapy (paclitaxel, carboplatin, MK-1775) or its analogs (i.e. cremophor, mannitol, etc). The MK-1775 Investigator Brochure can be referenced for information regarding study therapy.

(1)A beteg jelenleg részt vesz, vagy részt vett egy vizsgálati szerrel vagy orvostechnikai eszközökkel folytatott vizsgálatban, a vizsgálati készítmény első bevételét megelőző 28 napon belül.
(2)Azon betegek, akiknek aktív központi idegrendszeri metasztázisuk van, és/vagy meningitis carcinomatosa-ban szenvednek, ki vannak zárva a vizsgálatból. Azonban a központi idegrendszeri metasztázis esetében, ha a betegek befejeztek egy teljes terápiát, alkalmasak lehetnek a vizsgálatban való részvételre, amennyiben klinikai szempontból az állapotuk stabil a vizsgálat kezdetét megelőzően 1 hónappal az alábbiak szerint: (1)új vagy nagyobbodó központi idegrendszeri metasztázisra utaló jel hiánya. (2)a beteg nem szed szteroidot vagy legalább 2 hete stabil szteroid dózison van
(3)A betegnek elsődleges központi idegrendszeri daganata van.
(4)A betegnek ismert túlérzékenysége vagy ellenjavalata van a lehetséges vizsgálati kezelés hatóanyagaira (paclitaxel, karboplatin, MK-1775) vagy annak analógjaira (cremophor, mannitol…stb) A vizsgálati kezelésről az MK-1775 Vizsgálói Kézikönyvben található információ.

E.5 End points

E.5.1

Primary end point(s)

Progression Free Survival (PFS) per Enhanced RECIST 1.1

Progressziómentes túlélés (PFS) az 1.1-es bővített RECIST verziója alapján.

E.5.1.1

Timepoint(s) of evaluation of this end point

PFS is defined as the time from randomization to progressive disease or death, whichever occurs earlier

A progressziómentes túlélés (PFS) alatt azt az időszakot értjük, ami a vizsgálatba történő randomizációtól a betegség progressziójáig vagy a beteg halálig tart, amely korábban következik be.

E.5.2

Secondary end point(s)

Progression-free Survival per RECIST 1.1, Objective Response Rate (Enhanced RECIST 1.1 + CA-125), and Overall Survival

Progressziómentes túlélés az 1.1-es RECIST verziója alapján, a terápiára adott objektív válaszarány (1.1.-es RECIST bővített verziója + CA-125) és általános túlélés.

E.5.2.1

Timepoint(s) of evaluation of this end point

Overall Survival is defined as the time from randomization to death due to any cause. Patients without documented death at the time of analysis will be censored at the date last known to be alive.

Az általános túlélés alatt a vizsgálatba történő randomizálástól a halálig tartó időszakot értjük, függetlenül a halál okától. Amennyiben az elemzés idején a beteg haláláról nincs dokumentáció, azt az utolsó időpontot veszik figyelembe, amikor tudott volt, hogy a beteg életben van.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

Yes

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Brazil

Canada

Germany

Hungary

Israel

Russian Federation

Sweden

Taiwan

United Kingdom

United States

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LPLV - 18-Sep-14

Utolsó beteg utolsó vizit- 2014-Szept-18.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

119

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

119

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

119

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2012-09-05

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-08-30

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-08-05

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IMP with orphan designation in the indication
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