Clinical Trials Register

Summary
EudraCT Number:	2015-000952-11
Sponsor's Protocol Code Number:	PR-30-5017-C
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2016-07-19
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

Germany - BfArM

A.2

EudraCT number

2015-000952-11

A.3

Full title of the trial

A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of Niraparib Maintenance Treatment in Patients with Advanced Ovarian Cancer Following Response on Front-Line Platinum-Based Chemotherapy

A.3.1

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

A.4.1

Sponsor's protocol code number

PR-30-5017-C

A.5.4

Other Identifiers

Name:

IND No.

Number:

100,996

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	TESARO, Inc., a GSK company
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	TESARO, Inc., a GSK company
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	TESARO, Inc., a GSK company
B.5.2	Functional name of contact point	Clinical Trial Mailbox
B.5.3	Address:
B.5.3.1	Street Address	1000 Winter Street, Suite 3300
B.5.3.2	Town/ city	Waltham
B.5.3.3	Post code	MA 02451
B.5.3.4	Country	United States
B.5.4	Telephone number	+117189168375
B.5.5	Fax number	+17819301312
B.5.6	E-mail	clinicaltrials@tesarobio.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	Yes
D.2.1.1.1	Trade name	ZEJULA
D.2.1.1.2	Name of the Marketing Authorisation holder	GlaxoSmithKline (Ireland) Limited
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Niraparib (GSK3985771)
D.3.4	Pharmaceutical form	Capsule, hard
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	Niraparib
D.3.9.1	CAS number	1038915-60-4
D.3.9.2	Current sponsor code	L-001946812-005R, L-001946812 and MK-4827
D.3.9.3	Other descriptive name	NIRAPARIB
D.3.9.4	EV Substance Code	SUB93448
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	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, hard
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

Homologous recombination deficiency advanced ovarian cancer

E.1.1.1

Medical condition in easily understood language

Homologous recombination deficiency advanced ovarian cancer

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	20.0
E.1.2	Level	PT
E.1.2	Classification code	10033128
E.1.2	Term	Ovarian cancer
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of this study is to evaluate the efficacy of niraparib versus placebo as maintenance treatment, as measured by progression-free survival (PFS), in patients with Stage III or IV ovarian cancer (including fallopian and peritoneal cancers) with a complete response (CR) or partial response (PR) following front-line platinum-based chemotherapy treatment.

E.2.2

Secondary objectives of the trial

• To evaluate additional measures of clinical benefit for niraparib versus placebo as maintenance treatment, such as OS, patient-reported
outcomes (PROs), time to first subsequent therapy (TFST), and time to
progression on the next anticancer therapy (PFS2).
• To evaluate the safety and tolerability of niraparib versus placebo

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Patients must be female ≥18 years of age, able to understand the
study procedures and agree to participate in the study by providing
written informed consent
2.a. Patients must have histologically diagnosed high-grade serous or
endometrioid, or high-grade predominantly serous or endometrioid
ovarian cancer, fallopian tube cancer, or primary peritoneal cancer that
is Stage III or IV according to FIGO criteria
3. Surgical criteria:
a. Patients with inoperable Stage III and IV disease are eligible;
b. All Stage IV patients with operable disease are eligible;
c. Patients with stage III or IV disease treated with neoadjuvant
chemotherapy and interval debulking surgery are eligible;
d. Patients with stage III disease who have visible residual disease after
primary debulking surgery are eligible .
4. Chemotherapy criteria:
a. Patients who have received intraperitoneal chemotherapy are eligible;
b. All patients treated with primary debulking surgery must have had ≥6
and ≤9 cycles of platinum-based therapy;
c. Patients must have had ≥2 post-operative cycles of platinum-based
therapy following interval debulking surgery;
d. Patients must have physician assessed CR or PR after ≥ 3 cycles of
therapy;
e. Any residual tumor after completion of chemotherapy must measure ≤
2 cm;
f. Patients must have either CA-125 in the normal range or CA-125
decrease by more than 90% during their front-line therapy that is stable
for at least 7 days (ie, no increase >15% from nadir)
5. Patients must be randomized within 12 weeks of the first day of the
last cycle of chemotherapy.
6. All patients must agree to undergo central tumor HRD testing.
a. The central HRD test result must be available for randomization as it is a stratification factor. Patients with documented gBRCA1 or gBRCA2 mutation or sBRCA1/2 mutation may be randomized without HRD test results
b. The tumor sample may be submitted for HRD testing prior to the screening period if it appears the patient is likely to meet other eligibility requirements. Patients are not required to have repeat HRD testing if HRD result is "not determined" (eg, due to insufficient tumor specimen)
c. Patients with known HRD test results from a commercially available source are allowed to participate in the study; however, they must still agree to submit a tumor sample for central HRD testing. The results of the central HRD testing must be available prior to randomization and must be used for stratification. Additional testing related to HRD may be performed on the sample used for screening and randomization post randomization. If there is inadequate tissue remaining subsequent to the screening analysis, sites may be requested to provide additional tissue
from the block used for screening purposes.
7. Patients of childbearing potential must have a negative serum or urine
pregnancy test (beta human chorionic gonadotropin [hCG]) within 7 days prior to receiving the first dose of study treatment
8. Patients must be postmenopausal, free from menses for >1 year,
surgically sterilized, or willing to use adequate contraception to prevent
pregnancy (see Appendix A) or must agree to abstain from activities that
could result in pregnancy throughout the study, starting with enrollment
through 180 days after the last dose of study treatment
9. Patients must have an Eastern Cooperative Oncology Group (ECOG)
performance status of 0 or 1
10. Patients must have adequate organ function, defined as follows
(Note: complete blood count [CBC] test should be obtained without
transfusion or receipt of stimulating factors within 2 weeks before
obtaining screening blood sample):
a. Absolute neutrophil count ≥ 1,500/μL
b. Platelets ≥ 100,000/μL
c. Hemoglobin ≥ 10 g/dL
d. Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or calculated
creatinine clearance ≥ 60 mL/min using the Cockcroft-Gault equation
e. Total bilirubin ≤ 1.5 x ULN
f. Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 x ULN
unless liver metastases are present, in which case they must be ≤ 5 x
ULN
11. All patients must agree to complete PROs during study and then at 4
weeks, 8 weeks, 12 weeks, and 24 weeks after EoT regardless of subsequent treatment
12. Patients must have formalin-fixed, paraffin-embedded tumor
samples available from the primary cancer or agree to undergo fresh
biopsy prior to study treatment initiation
13. Patients must be able to take oral medications
14. Patients must agree to blood samples during screening and at the
end of treatment (EOT) for cytogenetic analysis

E.4

Principal exclusion criteria

1. Patient has mucinous or clear cell subtypes of epithelial ovarian
cancer, carcinosarcoma or undifferentiated ovarian cancer
2. Patient is Stage III disease who have had complete cytoreduction
(i.e., no visible residual disease) after primary debulking surgery
3. Patient has undergone more than two debulking surgeries
4. Patient is pregnant, breastfeeding, or expecting to conceive children,
while receiving study treatment and for up to 180 days after the last dose of
study treatment
5. Patient has a known hypersensitivity to the components of niraparib
or its excipients
6. Patient is simultaneously enrolled in any clinical trial of niraparib or
any other investigational therapy
7. Patient has received prior treatment with a known PARP inhibitor or
has participated in a study where any treatment arm included
administration of a known PARP inhibitor
8. Patient is to receive bevacizumab as maintenance treatment. Patients
who have received bevacizumab with their first-line platinum based
therapy but are unable to receive bevacizumab as maintenance therapy
due to adverse events or for any other reason are not excluded from
study as long as the last dose of bevacizumab was received ≥ 28 days
prior to signing the main informed consent form;
9. Patient has had investigational therapy administered within 4 weeks,
or within a time interval less than at least 5 half-lives of the
investigational agent, whichever is longer, prior to the first scheduled
day of dosing in this study
10. Patient has had any known ≥Grade 3 anemia, neutropenia or
thrombocytopenia due to prior chemotherapy that persisted >4 weeks
11. Patient has any known history or current diagnosis of MDS or AML;
12. Patient has undergone major surgery (per Investigator judgment)
within 3 weeks of starting the study or patient has not recovered from
any effects of any major surgery;
13. Patient has had drainage of ascites within 4 weeks prior to
enrollment;
14. Patient has undergone palliative radiotherapy encompassing >20%
of the bone marrow within 1 week of the first dose of study treatment;
15. Patient has a condition (such as transfusion dependent anemia or
thrombocytopenia), therapy, or laboratory abnormality that might
confound the study results or interfere with the patient's participation
for the full duration of the study treatment, including:
a. Patient received a transfusion (platelets or red blood cells) within 2
weeks of the first dose of study treatment;
b. Patient received colony-stimulating factors (eg, granulocyte colony
stimulating factor [G-CSF], granulocyte macrophage colony-stimulating
factor [GM-CSF] or recombinant erythropoietin) within 2 weeks prior to
the first dose of study treatment.
16. Patient is planning to donate blood during the study or for 90 days
after the last dose of study treatment.
17. Patient has been diagnosed and/or treated for invasive cancer less
than 5 years prior to study enrollment. Note: Patients with definitively
treated uterine cervical or urinary tract carcinoma in situ, nonmelanomatous
skin cancer or ductal carcinoma in situ (DCIS) of the breast are not excluded
18. Patient has known brain or leptomeningeal metastases that are
untreated or uncontrolled (ie, new or worsening symptom or signs, or
unstable steroid requirements)
19. Patient is considered a poor medical risk due to a serious,
uncontrolled medical disorder, nonmalignant systemic disease, or active,
uncontrolled infection
20. Patient is immunocompromised (patients with splenectomy are
allowed)
21. Patient has known, active hepatic disease (ie, hepatitis B or C)
22. Patient has a corrected QT interval (QTc) prolongation > 480
milliseconds at screening

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint is PFS, defined as the time from treatment randomization to the earlier date of assessment of progression or death by any cause in the absence of progression.

E.5.1.1

Timepoint(s) of evaluation of this end point

Date of assessment of progression or death by any cause in the absence of progression

E.5.2

Secondary end point(s)

The secondary endpoints include the following:
• OS
• Observed changes from baseline in the following PROs:
− FOSI
− EQ-5D-5L
− EORTC-QLQ-C30
− EORTC-QLQ-OV28
• Time to first subsequent therapy (TFST)
• PFS2

E.5.2.1

Timepoint(s) of evaluation of this end point

Per Protocol

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

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

- To evaluate potential biomarkers of PARP inhibitor sensitivity and tolerability
- To explore the relationship between HRD status and platinum sensitivity in ovarian cancer patients who have initial response to frontline platinum therapy

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)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

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

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

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

116

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

Switzerland

Ukraine

Canada

Israel

Russian Federation

United Kingdom

United States

Belgium

Czechia

Denmark

Finland

France

Germany

Hungary

Ireland

Italy

Norway

Poland

Spain

Sweden

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

LVLS

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:

574

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

468

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

438

F.4.2.2

In the whole clinical trial

1042

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)

According to the clinical trial protocol (see section 3 and 7).

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

2016-08-17

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-01-04

P. End of Trial
P.	End of Trial Status	Ongoing

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