A study to assess the feasibility of treating patients with gestational trophoblastic neoplasia with pre-surgical pembrolizumab prior to their second evacuation and determine if this is a desirable alternative

Plain English summary of protocol

Background and study aims
Gestational trophoblastic diseases (GTD) are a group of rare, pregnancy-related diseases of the placenta which can range from pre-cancerous growths to cancers that can be fatal if left untreated. Most patients with GTD are diagnosed at the precancerous stage early in pregnancy and undergo surgical removal of the disease from the womb. Around 15% of patients are not cured by surgical removal alone and need further treatment with chemotherapy or second surgery. Roughly one-third of patients are cured with a second surgery. Anticancer treatment with chemotherapy carries many short- and long-term side effects that can negatively affect a person’s quality of life. Finding less harmful therapies that can be paired with surgery could therefore be of great benefit to patients with recurrent GTD. One alternative is to pair surgery with another class of anticancer treatment, known as immunotherapy. Immunotherapy drugs such as pembrolizumab work by activating the body’s natural immune defences to fight the cancer. Pembrolizumab is an extremely effective and safe treatment for patients with more advanced GTD and an attractive alternative to more toxic chemotherapies. This study aims to determine how feasible it is to give pembrolizumab prior to the second surgery. The study will determine if we are able to recruit patients and if treatment can be safely delivered. Patients will be closely monitored and the researchers will collect tissues that will help them to understand better how cancers escape the immune system and how immunotherapy works.

Who can participate?
Patients aged 18 years and over with gestational trophoblastic neoplasia

What does the study involve?
Participants are randomly allocated to receive second surgery alone or to receive a single dose of pembrolizumab followed by surgery. All participants will be followed up for a year after the date of their surgery.

What are the possible benefits and risks of participating?
There is a possibility of redness, swelling and bruising after collection and participants may feel lightheaded or faint. For the second evacuation only arm the blood sample taken during pre-screening is what would usually be performed if the patient was undergoing standard-of-care treatment. No further blood samples are to be performed beyond this point besides blood collection for research. Only one small tube of blood will be collected at these time points. For the pembrolizumab group, blood sampling will be performed at pre-screening and the Day 11, 6-week and 12-week visits. These blood tests are important to ensure no adverse consequences of the IMP and to ensure patient safety. Furthermore, as the surgical evacuation in this arm is being performed at 14 days instead of the 7 as in the second evacuation arm, it is important to ensure hCG levels have not increased to a level where more prompt and aggressive treatment is needed.
Pembrolizumab is a common treatment for NSCLC. The common side effects are related to the immune system and include itching/rash, diarrhoea, cough, muscle/joint pain, fever, abdominal pain, sickness, headache and tiredness. This treatment is not yet licenced to be used in this setting, however, a global cohort of 58 patients with advanced gestational trophoblastic neoplasia (GTN) who were treated with pembrolizumab demonstrated a 70% cure rate. Furthermore, in the standard of care setting, pembrolizumab is given at a dose of 200 mg IV every 3 weeks or 400 mg every 6 weeks. In this study the patients will simply be received a single 200 mg IV dose, limiting the chance of any toxicities or adverse reactions.
Being exposed to X-rays does carry a risk of causing cancer many years or decades later, but this risk is thought to be very small. For example, an X-ray of the chest, limbs or teeth is equivalent to a few days' worth of background radiation and has less than a 1 in 1,000,000 chance of causing cancer. Participants will only undergo a single x-ray during the screening portion of the study.
Second evacuation by ultrasound-guided suction curettage is considered to be a safe approach in suitably selected patients and adverse side effects are deemed extremely unlikely but can include bleeding from the cervix or infection of the uterus; again, both are deemed very rare. All patients that undergo evacuation will be closely monitored.
MRI scans use powerful magnets and a computer to produce detailed images of any part of the body; these scans do not use X-rays. No short-term side effects have been found with MRI scans however patients may feel uncomfortable during a scan as they will have to remain very still throughout the procedure and may have feelings of claustrophobia whilst within the MRI machine. In some cases, a contrast medium/dye will be injected intravenously (into a vein) as part of the scan; this dye is used to improve the quality of the images. MRI contrast medium is generally very safe and side effects are uncommon but can occur.
Incidental findings are defined as observations of potential clinical significance unexpectedly discovered in research participants and unrelated to the purpose of the study. These may include for example abnormal or unexpected findings from laboratory samples or from radiology images.
The researchers do not expect many incidental findings to be identified during this study. However, any incidental findings discovered would be reported back by the Chief Investigator and study team to the participant’s treating oncologist and the participant themselves in writing. This may for example include any results from the translational analysis conducted.
If an incidental finding is observed during the study, and it is considered a significant abnormality, then the study team should report these to the PI who should take action accordingly. It is the PI’s responsibility to ensure findings are communicated to the participant, GPs or other clinicians as appropriate. Incidental findings should be reported to the sponsor trials team.
The patient population for this study will be women of childbearing age. All of the cohort have an elevated hCG, which is the marker normally used to define pregnancy but is also high in gestational cancer. At pre-screening, elevated hCG is confirmed with a blood test. Pregnancy is ruled out with the USS also done during pre-screening: the USS shows there is cancer and not a fetus in the uterus. The researchers have also included “pregnancy” as an exclusion criterion.

Where is the study run from?
Imperial College London (UK)

When is the study starting and how long is it expected to run for?
February 2023 to February 2026

Who is funding the study?
1. NIHR Imperial Biomedical Research Centre (UK)
2. Cancer Treatment and Research Trust (UK)

Who is the main contact?
resolve@imperial.ac.uk

Contact information

Study information

Eligibility

Locations

Countries of recruitment

• England
• United Kingdom

Study participating centre

Sponsor information

Imperial College London
University/education

5th Floor
Roderic Hill Building
London
SW7 2AZ
England
United Kingdom

Phone	+44 (0)2033117740
Email	rgit.ctimp.team@imperial.ac.uk
Website	http://www.imperial.ac.uk/
"ROR"	https://ror.org/041kmwe10

Funders

Funder type

Government

Results and Publications

Study outputs

Additional files

ISRCTN86152317_Protocol_v2.0_10July2023.pdf

Editorial Notes

06/02/2025: The recruitment end date was changed from 28/02/2025 to 31/07/2025.
10/07/2024: The following changes were made to the study record:
1. The recruitment start date was changed from 28/09/2023 to 14/02/2024.
2. The recruitment end date was changed from 31/07/2024 to 28/02/2025.
3. The overall study end date was changed from 01/08/2025 to 28/02/2026.
4. The intention to publish date was changed from 01/08/2026 to 28/02/2027.
14/08/2023: The following changes have been made:
1. Uploaded protocol (not peer reviewed).
2. Ethics approval was added.
3. The recruitment start date has been changed from 01/08/2023 to 28/09/2023.
08/08/2023: Internal review.
27/07/2023: ISRCTN received notification of combined HRA/MHRA approval for this trial on 27/07/2023.
24/02/2023: Trial's existence confirmed by the HRA.