Clinical Trials Register

Summary
EudraCT Number:	2017-003792-63
Sponsor's Protocol Code Number:	UCL/17/0629
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	GB - no longer in EU/EEA
Date on which this record was first entered in the EudraCT database:	2018-09-06
Trial 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

UK - MHRA

A.2

EudraCT number

2017-003792-63

A.3

Full title of the trial

Phase II trial of maintenance pembrolizumab following weekly paclitaxel for recurrent ovarian, fallopian tube or peritoneal cancer

A.3.1

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

PROMPT is a research study investigating patients with recurrent ovarian, fallopian tube or peritoneal cancer, who have previously been treated with weekly paclitaxel. This study will address whether such patients may benefit from maintenance treatment with pembrolizumab.

A.3.2

Name or abbreviated title of the trial where available

PROMPT

A.4.1

Sponsor's protocol code number

UCL/17/0629

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT03430700

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	University College London
B.1.3.4	Country	United Kingdom
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	Merck Sharp & Dohme Limited
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Cancer Research UK & UCL Cancer Trials Centre
B.5.2	Functional name of contact point	PROMPT Trial Coordinator
B.5.3	Address:
B.5.3.1	Street Address	90 Tottenham Court Road
B.5.3.3	Post code	W1T 4TJ
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	02076799872
B.5.5	Fax number	08076799871
B.5.6	E-mail	ctc.prompt@ucl.ac.uk

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	United Kingdom
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	Pembrolizumab
D.3.2	Product code	MK-3475
D.3.4	Pharmaceutical form	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	Pembrolizumab
D.3.9.1	CAS number	1374853-91-4
D.3.9.2	Current sponsor code	MK-3475
D.3.9.3	Other descriptive name	Anti-PD-1 monoclonal antibody
D.3.9.4	EV Substance Code	AS1
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	25
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.3.11.13.1	Other medicinal product type	Monoclonal antibody
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	Yes
D.2.1.1.1	Trade name	Keytruda
D.2.1.1.2	Name of the Marketing Authorisation holder	Merck Sharp & Dohme B.V.
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	Keytruda
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	Pembrolizumab
D.3.9.1	CAS number	1374853-91-4
D.3.9.3	Other descriptive name	SUB167136
D.3.9.4	EV Substance Code	AS2
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	25
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)	Yes
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

recurrent ovarian/fallopian tube or primary non-mucinous peritoneal 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	21.1
E.1.2	Level	PT
E.1.2	Classification code	10066697
E.1.2	Term	Ovarian cancer recurrent
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

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	10016180
E.1.2	Term	Fallopian tube 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

To investigate whether pembrolizumab significantly extends the length of time (during and after treatment) that a patient lives with cancer without it getting worse.

E.2.2

Secondary objectives of the trial

We will investigate the following:
- The length of time a patient lives with cancer without it getting worse
- How long patients live
- In how many patients does the cancer shrink
- Side effects of pembrolizumab
- Details of any further treatment if the cancer gets worse

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Patients must have a diagnosis of high grade recurrent ovarian/fallopian tube or primary non-mucinous peritoneal cancer

2. Be willing and able to provide written informed consent for the trial, indicating that the patient has been informed of and understands the experimental nature of the study, possible risks and benefits, trial procedures, and alternative options

3. Be  18 years of age on day of signing informed consent
4. Patients should be treated with at least 4 cycles of weekly paclitaxel for their first non-platinum-based therapy. [Non-platinum-based therapy given for CT/MR documented recurrence where further platinum therapy considered unsuitable]
5. Patients can have had up to 3 prior lines of treatment for ovarian cancer before starting weekly paclitaxel
6. Patients must have achieved at least stable disease or response to a minimum for four cycles of weekly paclitaxel (measured by CT/MR)

7. Trial treatment must start within 8 weeks after last paclitaxel dose

8. Availability of archival tissue

9. Patient has disease amenable to biopsy after paclitaxel

10. Patient is willing to have a biopsy at baseline and before start of the 4th cycle of pembrolizumab

11. CT chest, abdominal and pelvic scan within 28 days of registration

12. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

13. Willing and able to comply with the protocol for the duration of the study, including the treatment plan, investigations required and follow up visits

14. Demonstrate adequate organ function as defined in Table 1 of protocol, all screening labs should be performed within 10 days of treatment initiation.

15. For patients of childbearing potential should have a negative urine or serum pregnancy test. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
16. For patients of childbearing potential (defined in Section 6.3.1) must be willing to use an adequate method of contraception as outlined in Section 6.3.4 from the start of treatment through to 4 months after the last dose of study medication

E.4

Principal exclusion criteria

1. Prior therapy with an anti-PD-1, anti-PD-L1 or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137)
2. Has a diagnosis of low grade or mucinous ovarian cancer
3. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment (n.b. the use of physiologic doses of corticosteroids may be approved after consultation with UCL CTC), excepting use of inhaled steroids.
4. Has a known history of active TB (Bacillus Tuberculosis)
5. Has known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known Hepatitis C virus (defined as HCV RNA [qualitative] is detected)*
6. Has a known history of Human Immunodeficiency Virus (HIV). *
7. Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks (could consider shorter interval for kinase inhibitors or other short half-life drugs) prior to randomisation.
Note: Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible.
Note: If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
8. Has received prior radiotherapy within 2 weeks of start of study treatment. 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.
9. Patients with concurrent or previous malignancy within the last 5 years (except Stage I grade 1 endometrial cancer; in situ cervical cancer; DCIS of the breast) that could compromise assessment of the primary or secondary endpoints of the trial
10. Active central nervous system (CNS) metastases and/or carcinomatous meningitis; patients with previously treated brain metastases may participate provided they are:
a) radiologically stable
b) without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening)
c) clinically stable
d) without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.

11. Has active autoimmune disease that required systemic treatment in past 2 years (i.e. with use of disease modifying agents, corticosteroids (at doses >10mg prednisolone daily or equivalent) or immunosuppressive drugs) except vitiligo or resolved childhood asthma/atopy. Replacement therapy (e.g. levothyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is permitted
12. Has a corrected serum calcium of >1.5 x ULN despite maximal anti-hypercalcaemic therapy
13. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis or has a history of interstitial lung disease
14. Has a newly diagnosed venous thrombotic event (e.g. PE, DVT) untreated with anticoagulation. Patients must have received at least 14 days of anticoagulation for a new thrombotic event and be suitable for continued therapeutic anticoagulation during trial participation. Patients are excluded if they have a history of arterial thrombosis
15. Has an active infection requiring systemic therapy
16. Has symptoms of bowel obstruction in the past three months
17. Any serious and/or unstable pre-existing medical, psychiatric or other condition that, in the treating clinician’s judgement could interfere with patient safety or obtaining informed consent
18. Has known psychiatric or substance abuse disorders that would interfere with co-operation with the requirements of the trial
19. Is pregnant or breastfeeding, or expecting to conceive children within the projected duration of the trial, starting with the screening visit through to 4 months after the last dose of trial treatment
20. Has received a live vaccine within 30 days of planned start of study treatment. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette–Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.

*Testing for Hepatitis and HIV is not required unless mandated by local health authority.

E.5 End points

E.5.1

Primary end point(s)

The primary outcome measure of the study is progression-free survival (PFS) rate at 6 months from the start of maintenance therapy

E.5.1.1

Timepoint(s) of evaluation of this end point

6 months from the start of maintenance therapy (pembrolizumab)

E.5.2

Secondary end point(s)

• Progression–free survival at 6 months from start of weekly paclitaxel
• Overall survival (from pembrolizumab and start of paclitaxel)
• Disease response

E.5.2.1

Timepoint(s) of evaluation of this end point

end of trial- 2 years from the registration of last patient

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

E.6.4

Safety

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

Yes

E.6.13.1

Other scope of the trial description

Immunological and biological studies

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

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

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