Clinical Trials Register

Summary
EudraCT Number:	2017-002805-36
Sponsor's Protocol Code Number:	ENGOT-OV30/NSGO
National Competent Authority:	Denmark - DHMA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2017-08-25
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

Denmark - DHMA

A.2

EudraCT number

2017-002805-36

A.3

Full title of the trial

NSGO-OV-UMB1; ENGOT-OV30: A phase II umbrella trial in patients with relapsed ovarian cancer.

A.3.1

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

Immunotherapy in ovarian cancer

A.3.2

Name or abbreviated title of the trial where available

ENGOT-OV30 / NSGO

A.4.1

Sponsor's protocol code number

ENGOT-OV30/NSGO

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	NSGO
B.1.3.4	Country	Denmark
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	AstraZeneca
B.4.2	Country	Sweden
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	NSGO
B.5.2	Functional name of contact point	Project Manager
B.5.3	Address:
B.5.3.1	Street Address	Dept of Oncology 9431, Rigshospitalet, Blegdamsvej 9
B.5.3.2	Town/ city	Copenhagen
B.5.3.3	Post code	2100
B.5.3.4	Country	Denmark
B.5.4	Telephone number	4535453311
B.5.5	Fax number	4535452898
B.5.6	E-mail	dorte.noervang@regionh.dk

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.2.1.2	Country which granted the Marketing Authorisation	Denmark
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	MEDI 9447
D.3.2	Product code	N/A
D.3.4	Pharmaceutical form	Powder for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	MEDI9447
D.3.9.1	CAS number	N/A
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	Yes
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.2.1.2	Country which granted the Marketing Authorisation	Denmark
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	Durvalumab
D.3.2	Product code	MEDI 4736
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	DURVALUMAB
D.3.9.1	CAS number	1428936-60-7
D.3.9.2	Current sponsor code	MEDI4736
D.3.9.4	EV Substance Code	SUB176342
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	Yes
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Ovarian cancer

E.1.1.1

Medical condition in easily understood language

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	HLT
E.1.2	Classification code	10033129
E.1.2	Term	Ovarian neoplasms malignant (excl germ cell)
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

The overall objective in part 1 is to obtain preliminary evidence of efficacy of novel agents for the management of relapsed ovarian cancer, and in part 2 efficacy of novel agents compared to the standard of care (SoC).
Disease control rate (DCR) (CR+PR+SD) according to RECIST v1.1 at 16 weeks.

E.2.2

Secondary objectives of the trial

• Progression-Free Survival (PFS) by RECIST v1.1: at 6 & 12 months and median PFS
• PFS by Immune-RECIST: at 6 & 12 months and median PFS
• Overall survival
• Objective response rate according to RECIST v1.1 (ORR)
• Duration of (Overall) Response (DoR)
• Safety and tolerability.4.3.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Inclusion criteria Cohort A
A patient will be eligible for inclusion only if all of the following criteria are fulfilled:
1. Platinum-sensitive disease: defined as disease progression ≥ 6 months following the last administered dose of platinum-based therapy. Patients must have received atleast one line of chemotherapy for platinum-sensitive disease. OR
2. Platinum-resistant disease: defined as disease progression < 6 months following the last administered dose of platinum-based therapy. OR
3. Platinum-refractory disease: defined as lack of response or disease progression while receiving the most recent therapy.

Other inclusion criteria
4. Histological confirmed ovarian, fallopian tube or peritoneal cancers.
5. Histological types: high-grade serious, high-grade endometriod, undifferentiated, carcinosarcoma or mixed histology.
6. Subjects must have at least 1 measurable lesion as defined by RECIST guidelines. This should not be the same lesion used for biopsy.
7. Patients entering cohort A: Archival tumour tissue must be screened for CD73 and only CD73 positive patients (defined as >10% of tumor cells positive) will enter this trial.
8. Patient agrees to undergo all analysis (blood, serum, tissue); radiological examinations according to protocol.
9. Mandatory tumour biopsy before treatment (before day 0) and at day 56 of treatment.
10. Patients must give informed consent.
11. Patients must be at least 18 years of age.
12. ECOG performance status 0-1
13. Serum albumin >30g/l.
14. Adequate organ function
o Absolute neutrophil count (ANC) ≥1,500/mcL (without growth factors for >21 days)
o Platelets >100,000/mcL (without platelet transfusion for >21 days)
o Hemoglobin ≥ 9g/dl (5.6 mmol/L), without blood transfusion for >21 days
o Serum creatinine ≤1.5x upper limit of normal (ULN) or calculated creatinine clearance ≥50mL/min using Cockcroft-Gault formula.
o Total bilirubin ≤1.5x ULN. Total bilirubin ≤3x ULN in the presence of liver metastases.
o Alanine  aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5x ULN unless liver metastases are present, in which case they must be ≤5x ULN.
15. Life expectancy of at least 12 weeks.
16. Patients must be fit to receive Investigational medical products (IMPs) (MEDI9447 + durvalumab).
17. Patients of child-bearing potential: who are sexually active must use at least one highly effective method of contraception from the time of screening, and must agree to continue using such pre-cautions for 90 days after the last dose of MEDI9447 + durvalumab combination therapy. Non-sterilised male partners of a female subject must use male condom plus spermicide throughout this period. Cessation of birth control after this point should be discussed with a responsible phy-sician. Not engaging in sexual activity for the total duration of the drug treatment and the drug washout period is an acceptable practice; however, periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception. Female subjects should re-frain from breastfeeding throughout this period.
18. All patients: Patients should not donate blood or blood components while participating in this study and through 90 days after receipt of the final dose of MEDI9447 + durvalumab combina-tion therapy.

E.4

Principal exclusion criteria

1. Subjects using immunosuppressive medications within 14 days prior to first dose with the excep-tion of topical (intranasal, inhaled, local injection, systemic (prednison equivalent 10 mg/day or less) or as needed for hypersentivity reactions such as CT scan premedication.
2. Immunodeficiency or organ transplant
3. Live vaccines within 28 days prior to the first dose.
4. Major surgery within 28 days prior to the first dose..
5. Ovarian sarcomas, small cell carcinoma with neuroendocrine differentiation, non-epithelial can-cers.
6. Cancer therapies (chemotherapy, radiotherapy, surgery, immunotherapy, biologic or hormonal therapy) within 28 days prior to the first dose.
7. Concurrent treatment with an investigational agent or participation in another clinical trial.
8. Previous malignant disease: patients are not eligible for the study if actively being treated of inva-sive cancer other than ovarian cancer. Patients with previous malignant disease other than ovarian cancer who are relapse-free and treatment-free for more than three years may enter this study. Pa-tients with previous history of in-situ carcinoma, stage 1A cervical cancer or non-invasive basal cell and squamous cell skin carcinoma can enter this trial.
9. Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, or human immunodeficien-cy virus (positive HIV 1/2 antibodies). Patients with a past or resolved HBV infection (defined as the presence of hepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
10. History of a cerebral vascular accident, transient ischemic attack or subarachnoid hemorrhage within the past 6 months.
11. History of clinically significant hemorrhage in the past 3 months.
12. Untreated CNS disease, leptomeningeal disease or cord compression. Subjects with treated dis-ease should have at least 4 weeks of neurologic and radiographic stability and be off of steroids for 14 days.
13. Significant cardiovascular disease’s, including uncontrolled hypertension, clinically relevant car-diac arrhythmia, unstable angina or myocardial infarction within 6 months prior to randomization, congestive heart failure > NYHA II, severe peripheral vascular disease, QT prolongation >470msec, clinically significant pericardial effusion.
14. Persistance of clinically relevant therapy related toxicity from previous anticancer therapy (any grade 3-4 toxicity or grade ≥2 neuropathy).
15. Known hypersensitivity to the trial drugs, or to their excipients.
16. Has had prior exposure to IMPs, or any other immunotherapy.
17. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease [eg, colitis or Crohn's disease], diverticulitis [with the exception of diverticulosis], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc]). The following are exceptions to this criterion:
− Patients with vitiligo or alopecia
− Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone re-placement
− Any chronic skin condition that does not require systemic therapy
− Patients without active disease in the last 5 years may be included but only after consulta-tion with the study physician
− Patients with celiac disease controlled by diet alone
18. For cohorts B and C: Medical condition requiring current systemic anticoagulation, or a history of congenital hypercoagulable condition. Subjects taking aspirin at doses < 325 mg per day are eli-gible provided that prothrombin time is within the institutional range of normal. Use of local anti-coagulation for port maintenance is permitted

E.5 End points

E.5.1

Primary end point(s)

• Disease control rate (DCR) (CR+PR+SD) at 16 weeks.

E.5.1.1

Timepoint(s) of evaluation of this end point

Every 8 weeks until disease progression

E.5.2

Secondary end point(s)

• Progression-Free Survival (PFS) by RECIST v1.1: at 6 & 12 months and median PFS
• PFS by Immune-RECIST at 6 & 12 months and median PFS
• Overall survival (OS)
• Objective response rate according to RECIST v1.1 (ORR)
• Duration of (Overall) Response (DoR)
• Safety and tolerability.

E.5.2.1

Timepoint(s) of evaluation of this end point

every 8 weeks until disease progression and registration of survival data

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

E.6.7

Pharmacodynamic

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

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

E.8.1.1

Randomised

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

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

E.8.2.3

Other

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

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

Canada

Japan

Korea, Republic of

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

01 Sep 2022

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

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:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

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

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
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	GCIG Gynecologic Cancer InterGroup
G.4.3.4	Network Country	Canada
G.4 Investigator Network to be involved in the Trial: 2
G.4.1	Name of Organisation	ENGOT European Network of Gynaecological Oncological Trial Groups
G.4.3.4	Network Country	Czech Republic

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2017-10-23

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-10-16

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2021-11-30

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