Clinical Trials Register

Summary
EudraCT Number:	2017-004168-36
Sponsor's Protocol Code Number:	UCL/17/0672
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:	2019-06-07
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

2017-004168-36

A.3

Full title of the trial

A phase II study of pembrolizumab in patients with advanced gynaecological clear cell cancer

A.3.1

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

A clinical study testing the effectiveness of an immunotherapy cancer drug called pembrolizumab, in patients who have progressed with gynaecological cancer, called clear cell cancer.

A.3.2

Name or abbreviated title of the trial where available

PEACOCC

A.4.1

Sponsor's protocol code number

UCL/17/0672

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT03425565

A.5.4

Other Identifiers

Name:

Funder's (MSD) reference

Number:

MISP 55357

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 Ltd
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	Laura Hughes
B.5.3	Address:
B.5.3.1	Street Address	90 Tottenham Court Road
B.5.3.2	Town/ city	London
B.5.3.3	Post code	W1T4TJ
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	02076799284
B.5.5	Fax number	02076799871
B.5.6	E-mail	ctc.peacocc@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.2.5	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.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

Advanced Gynaecological Clear Cell Cancer

E.1.1.1

Medical condition in easily understood language

Gynaecological clear cell cancer is a rare cancer which has spread (progressed) from the ovary(ies), fallopian tube), womb, vaginal, vulva or cervix.

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	21.0
E.1.2	Level	LLT
E.1.2	Classification code	10048683
E.1.2	Term	Advanced cancer
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	21.1
E.1.2	Level	PT
E.1.2	Classification code	10009252
E.1.2	Term	Clear cell endometrial carcinoma
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	10033128
E.1.2	Term	Ovarian cancer
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 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.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10046885
E.1.2	Term	Vaginal cancer
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	10047741
E.1.2	Term	Vulval cancer
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	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10008229
E.1.2	Term	Cervical 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 assess whether pembrolizumab can control or reduce tumour safely and effectively in a significant number of women at 12 weeks (progression free survival rate) with advanced clear cell gynaecological cancer.

E.2.2

Secondary objectives of the trial

• To assess whether the study drug pembrolizumab prolongs the time it takes before the cancer grows on study on study and/or prolongs the patients' survival.
• To assess whether a second treatment period with pembrolizumab prolongs the time it takes before the cancer grows back and/or prolongs the patients' survival.
• To assess the effect of pembrolizumab on the overall tumour response rate at 12 weeks, and best tumour response rate over the entire study.
• To assess the duration of response.
• To assess quality of life during treatment with pembrolizumab.
• To assess any side-effects of the drug.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Histological diagnosis of advanced gynaecological cancer including ovarian (including primary peritoneal and fallopian tube), endometrial, vaginal, vulval or cervical cancer.
2. Be willing and able to provide written informed consent/assent for the trial.
3. Age ≥18 years.
4. Patient must have at least one measurable lesion according to RECIST v1.1 in addition to a separate biopsiable lesion. Measurable lesions should be outside any prior radiation field unless progression has occurred at that site.
5. Have measurable disease according to RECIST v1.1.
6. Evidence of radiological disease progression.
7. Patient is willing to provide archival tissue.
8. ECOG Performance Status 0 or 1.
9. Patient has a life expectancy of at least 4 months from consent.
10. Received ≥ 1 line of prior chemotherapy.
11. Demonstrate adequate organ function.
12. For patients of childbearing potential, negative urine or serum pregnancy test prior to receiving the first dose of study medication.
13. Patients of childbearing potential must be willing to use a highly effective method of contraception for the study duration required.

E.4

Principal exclusion criteria

1. Patient is currently participating in and receiving other study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
2. Prior anti-cancer monoclonal antibody (mAb), chemotherapy or targeted small molecule therapy within 4 weeks prior to study treatment Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
3. Radiation therapy within 2 weeks prior to starting study treatment.
4. Prior therapy with an anti-PD-1, anti-PD-L1 or anti-PD-L2 agent.
5. Known diagnosis of immunodeficiency or is receiving systemic steroid therapy at doses > 10mg prednisolone daily or equivalent or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
6. Has a known history of active bacillus tuberculosis (TB).
7. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] detected) infection.
8. Known history of Human Immunodeficiency Virus (HIV) (HIV type 1/2 antibodies).
9. Known hypersensitivity to pembrolizumab or any of its excipients.
10. Known additional malignancy that is progressing or requires active treatment. If there is a history of a second malignancy and there is doubt regarding the aetiology of progressive disease, then a biopsy is required to determine the diagnosis.
11. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
12. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids (at a dose >10mg predisolone daily or equivalent) or immunosuppressive drugs).
13. Corrected serum calcium of grade 1 hypercaelcemia (>2.9 mmol/L) despite maximal antihypercalcaemic therapy.
14. Has a known history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
15. Newly diagnosed venous thromboembolic event (eg pulmonary embolism, deep vein thrombosis DVT), unless patient has received at least 14 days of therapeutic dose anticoagulation for a new thromboembolic event and is suitable for continued therapeutic anticoagulation during trial participation.
16. History of arterial thrombosis (excluding the pulmonary artery), within 12 months prior to registration (if beyond 12 months prior to registration, patient may be included providing they have fully recovered clinically).
17. Active infection requiring systemic therapy (for example antibiotics, antivirals, antifungals).
18. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient’s participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating investigator.
19. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
20. Pregnant or breastfeeding.
21. Has received a live vaccine within 30 days prior to the planned start of trial treatment.
22. Has been hospitalised for bowel obstruction within 4 weeks prior to registration.
23. Current abdominal/pelvic fistulation.

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint is progression free survival (PFS) rate at 12 weeks. This population of patients has very poor survival in the second line setting, therefore an improvement in survival at 12 weeks is a meaningful outcome. PFS rate also captures patients that have stable disease, which may be the earliest indication of benefit with an immunotherapeutic agent.

E.5.1.1

Timepoint(s) of evaluation of this end point

The evaluation of the primary outcome measure will be 12 weeks from the start of the patient's treatment.

The number of patients with complete or partial response or stable disease maintained at 12 weeks will be considered as having progression free survival at 12 weeks.

E.5.2

Secondary end point(s)

1. Progression-free survival (PFS)

2. Time to second disease progression (Re-treatment period)
Time to second disease progression refers to second progression in patients re-treated on trial post first progression. All deaths will be included, whether they occur during the re-treatment period or following treatment discontinuation. For patients who have not died or progressed, progression-free survival will be censored at the date of last contact.

3. Overall survival.

4. Objective response rate at 12 weeks and best objective response rate
Objective response is defined as a complete or partial tumour response as determined by RECIST v1.1. The best objective response consists of the best among all objective responses assessed.

5. Duration of Response
For patients with an objective response, duration of objective response is defined as the time from initial complete or partial response to disease progression or death on study from any cause (defined as death within 30 days of the last study treatment), whichever occurs first.

For patients with disease control (objective response or stable disease maintained ≥12 weeks), duration of disease control is defined as the time from start of treatment to disease progression or death on study from any cause (defined as death within 30 days of the last study treatment), whichever occurs first.

6. Safety Monitoring
All patients who received at least one cycle of pembrolizumab will be included in the safety analysis. Adverse events (AEs) will be monitored on an ongoing basis and their frequencies reported. AEs will be categorized using the NCI Common Terminology Criteria for Adverse Events (CTCAE), version 5. The worst event for each patient will be described. Both events related and unrelated to treatment will be captured.

7. Quality of Life (QoL)
The questionnaire used will be FACT-O (version 4). QoL data will be analysed using methods for repeated measures. The algorithm for core construction will be based on that provided by the FACT-O manual.

E.5.2.1

Timepoint(s) of evaluation of this end point

1. PFS is defined as the time from start of treatment to progression or death from any cause (whichever comes first).

2. Time to second disease progression is defined as the time from diagnosis of first progression to second progression, or death from any cause (whichever comes first).

3. Overall Survival
Overall survival is defined as the time from start of treatment to death from any cause.

4. Objective Response Rate (at 12 weeks and best) will be calculated from the start of treatment.

5. Duration of response will be evaluated from the time of initial response until progression or death on trial.

6. Safety monitoring will be evaluated from consent until the last patient's visit.

7. QoL
Mean scores will be presented at each time point, as well as changes from baseli

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

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

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.8.5.1

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

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