Gestational Trophoblastic DiseasePhase 2NCT05635344
A Feasibility Window Study of Pembrolizumab Prior to Second Evacuation for Post-molar Gestational Trophoblastic Neoplasia
A Phase 2 study testing Pembrolizumab in people with Gestational Trophoblastic Disease and Gestational Trophoblastic Neoplasia, run by Imperial College London at 1 site in United Kingdom.
Trial summary
Gestational Trophoblastic Diseases (GTD) are a variety of rare, pregnancy related cell multiplication disorders of cells of the placenta which can range from pre-cancerous growths to more serious lesions that can spread to nearby tissues that can cause serious health issues. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Gestational Trophoblastic Disease, Gestational Trophoblastic Neoplasia, Gestational Trophoblastic Tumor, Recurrent
- What is being tested?
- Pembrolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 14 Feb 2024to 1 Aug 2026
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent prior to initiation of any study procedures and willingness and ability to comply with the study schedule.
- Age ≥18yrs
- Postmolar GTN defined as recurrence or persistence of histologically confirmed CHM after primary surgical evacuation with no intervening treatment.
- Postmolar GTN defined as plateau or rising human chorionic gonadotropin (hCG). Plateaued hCG is defined as four or more equivalent values of hCG over at least 3 weeks. Rising hCG is defined as two consecutive rises in hCG of 10% or greater over at least 2 weeks.
- hCG under 20,000 IU/L
- Low risk disease as defined by the Federation of Obstetrics and Gynecology (FIGO) 2000 risk scoring criteria (score of 6 or less)
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- No metastatic disease on chest X-ray.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- Disease present within the uterine cavity not within 5mm of the serosal surface.
- Adequate bone marrow reserve or organ function as defined by any one of the following parameters:
- Absolute neutrophil count ≥ 1.5 x 10^9 /L;
- Platelet count ≥ 100 x 10^9 /L;
- Haemoglobin ≥ 9.0 g/dL (may have been blood transfused)
- Creatinine clearance ≥ 30 ml/min (Cockcroft-Gault formula)
- Serum bilirubin ≤ 1.5 x ULN
- AST/ALT ≤ 2.5 X ULN
- All patients must agree to a highly effective method of contraception, or to complete abstinence* for 1 year following second evacuation. This is standard practice following second evacuation of GTN because hCG levels rise in pregnancy thus masking a potential cancer recurrence
Who cannot join
- Patients with other invasive malignancies, with the exception of non-melanoma skin cancer, patients who have had any evidence of the other cancer present within the last 2 years or patients whose previous cancer treatment contraindicates this protocol therapy.
- Patients with histologically confirmed choriocarcinoma, placental site trophoblastic tumor (PSTT) or epithelioid trophoblastic tumor (ETT) on the first curettage.
- Pregnant women.
- Uncontrolled vaginal bleeding.
- Administration of live vaccine within 30 days prior to the first dose of study drug. 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.
- History of immunodeficiency or receiving chronic 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 study drug.
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- Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
- History of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
- History of Human Immunodeficiency Virus (HIV) infection.
- 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] is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required unless mandated by local health authority.
- History of active TB (Bacillus Tuberculosis).
- History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
- History of allogenic tissue/solid organ transplant.
Trial locations and contacts
1 site in 1 country.
Philip Badman contact
United Kingdom1 site, 1 recruiting
- Recruiting
Imperial College Healthcare NHS Trust
London, W6 8RF
Dr Ghorani, e.ghorani@imperial.ac.uk
About this study
Gestational Trophoblastic Diseases (GTD) are a variety of rare, pregnancy related cell multiplication disorders of cells of the placenta which can range from pre-cancerous growths to more serious lesions that can spread to nearby tissues that can cause serious health issues.
Most patients that develop GTD are diagnosed at the precancerous stage early in pregnancy and undergo surgical removal of the disease from the uterus. Around 15% of patients are not cured by surgical removal alone and need to undergo further treatment with chemotherapy or further surgery; of which roughly one-third of patients are cured with a second round of surgery alone.
Read more
Anti-cancer treatment with chemotherapy carries many short- and long-term side effects that can negatively affect a person's quality of living. Finding less harmful anticancer therapies that can be paired with surgery is therefore of great benefit to patients with recurrent GTD.
An alternative is to pair surgery with another class of anticancer treatments, known as immunotherapies. Immunotherapy aims to encourage the bodies natural defences to fight the cancer cells.
Pembrolizumab, an immunotherapeutic agent which works by preventing cancer cells from hiding from the immune system; has been proven to be an extremely safe form of anticancer therapy and is an attractive alternative to more toxic chemotherapeutic agents.
The RESOLVE study aims to determine how feasible it is to deliver pre-surgical pembrolizumab to patients and determine if this is a desirable alternative; potentially leading to a larger more definitive study.
20 patients will be recruited onto the study and will be evenly split into two arms:
- 10 patients to receive second evacuation alone
- 10 patients to receive single dose of Pembrolizumab followed by surgery All patients that take part in the study will be recruited from Charing Cross Hospital and will be followed up for a year after the date of their surgery.
- Conditions
- Gestational Trophoblastic Disease, Gestational Trophoblastic Neoplasia, Gestational Trophoblastic Tumor, Recurrent
- Being tested
- Pembrolizumab
- Medical subject headings
- Gestational Trophoblastic Disease, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
Single dose 200mg dose of Pembrolizumab given intravenously
| Study group | Role | What they receive |
|---|---|---|
| Second evacuation only | No intervention | Patients that are randomised onto this arm of the study will be treated by second evacuation ALONE. |
| Pembrolizumab and second evacuation | Experimental | Patients that are randomised onto this arm will be given a single dose of Pembrolizumab in a neoadjuvant setting followed by second evacuation Receives: Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the feasibility of conducting a definitive study of neoadjuvant pembrolizumab prior to second evacuation of low risk postmolar gestational trophoblastic neoplasia (GTN)
Outcome will be measured by determining the proportion of eligible patients who consent to randomisation and the proportion of patients randomised to the intervention arm who complete protocol treatments.
From this, it can be gauged how feasible it would be to open and recruit to a large scale more definitive study on using pembrolizumab in a neoadjuvant setting in GTN.
Measured: 1 year
Secondary outcomes (2)
To assess the rate of surgical cure with and without pembrolizumab.
Proportion of patients who achieve a sustained complete response (no recurrence of disease) following second evacuation and no further anti-cancer therapy. This defined as normalisation of hCG and no rise by 1 year post procedure. Failure of second evacuation resulting in disease control defined by national guidelines is described as a rise or plateau in hCG, hCG over 20,000 IU/L at 4 weeks or heavy vaginal bleeding. The response rates of patients post second evacuation will be compared across both arms.
Measured: 1 year
To assess the safety of a single dose of pembrolizumab prior to second evacuation versus second evacuation alone.
Incidence of adverse effects of second evacuation and pembrolizumab within 30 days and 12 weeks respectively, assessed by Common Terminology Criteria for Adverse Events (CTCAE v5.0, 27 Nov 2017).
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Dec 2022
- Study start14 Feb 2024
- Primary completion1 Feb 2026 (estimated)
- Study completion1 Aug 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Gestational Trophoblastic DiseaseStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Collaborators
- Cancer Research UK
- Responsible party
- Sponsor
- Investigators
- Ehsan Ghorani, Study chair, Imperial College London University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05635344
- Sponsor's protocol ID
- C/43/2022
- Other IDs
- 2022-002986-14
- Status last verified
- Apr 2024
- First submitted
- 22 Nov 2022
- Last updated
- 17 Apr 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Feasibility Window Study of Pembrolizumab Prior to Second Evacuation for Post-molar Gestational Trophoblastic Neoplasia
- ClinicalTrials.gov ID
- NCT05635344
- Acronym / sponsor ID
- C/43/2022
- Conditions
- Gestational Trophoblastic Disease, Gestational Trophoblastic Neoplasia, Gestational Trophoblastic Tumor, Recurrent
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Collaborators
- Cancer Research UK
- Study start
- 14 Feb 2024 (actual)
- Primary completion
- 1 Feb 2026 (estimated)
- Study completion
- 1 Aug 2026 (estimated)
- First posted
- 2 Dec 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Gestational Trophoblastic Diseases (GTD) are a variety of rare, pregnancy related cell multiplication disorders of cells of the placenta which can range from pre-cancerous growths to more serious lesions that can spread to nearby tissues that can cause serious health issues.
Most patients that develop GTD are diagnosed at the precancerous stage early in pregnancy and undergo surgical removal of the disease from the uterus. Around 15% of patients are not cured by surgical removal alone and need to undergo further treatment with chemotherapy or further surgery; of which roughly one-third of patients are cured with a second round of surgery alone.
Anti-cancer treatment with chemotherapy carries many short- and long-term side effects that can negatively affect a person's quality of living. Finding less harmful anticancer therapies that can be paired with surgery is therefore of great benefit to patients with recurrent GTD.
An alternative is to pair surgery with another class of anticancer treatments, known as immunotherapies. Immunotherapy aims to encourage the bodies natural defences to fight the cancer cells.
Pembrolizumab, an immunotherapeutic agent which works by preventing cancer cells from hiding from the immune system; has been proven to be an extremely safe form of anticancer therapy and is an attractive alternative to more toxic chemotherapeutic agents.
The RESOLVE study aims to determine how feasible it is to deliver pre-surgical pembrolizumab to patients and determine if this is a desirable alternative; potentially leading to a larger more definitive study.
20 patients will be recruited onto the study and will be evenly split into two arms:
- 10 patients to receive second evacuation alone
- 10 patients to receive single dose of Pembrolizumab followed by surgery All patients that take part in the study will be recruited from Charing Cross Hospital and will be followed up for a year after the date of their surgery.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Second evacuation only | No intervention | –Patients that are randomised onto this arm of the study will be treated by second evacuation ALONE. |
| Pembrolizumab and second evacuation | Experimental | Drug: PembrolizumabPatients that are randomised onto this arm will be given a single dose of Pembrolizumab in a neoadjuvant setting followed by second evacuation |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Written informed consent prior to initiation of any study procedures and willingness and ability to comply with the study schedule.
- Age ≥18yrs
- Postmolar GTN defined as recurrence or persistence of histologically confirmed CHM after primary surgical evacuation with no intervening treatment.
- Postmolar GTN defined as plateau or rising human chorionic gonadotropin (hCG). Plateaued hCG is defined as four or more equivalent values of hCG over at least 3 weeks. Rising hCG is defined as two consecutive rises in hCG of 10% or greater over at least 2 weeks.
- hCG under 20,000 IU/L
Key exclusion criteria (13 listed)
- Patients with other invasive malignancies, with the exception of non-melanoma skin cancer, patients who have had any evidence of the other cancer present within the last 2 years or patients whose previous cancer treatment contraindicates this protocol therapy.
- Patients with histologically confirmed choriocarcinoma, placental site trophoblastic tumor (PSTT) or epithelioid trophoblastic tumor (ETT) on the first curettage.
- Pregnant women.
- Uncontrolled vaginal bleeding.
- Administration of live vaccine within 30 days prior to the first dose of study drug. 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PembrolizumabSingle dose 200mg dose of Pembrolizumab given intravenously | Drug | Pembrolizumab and second evacuation |
Primary outcome
To determine the feasibility of conducting a definitive study of neoadjuvant pembrolizumab prior to second evacuation of low risk postmolar gestational trophoblastic neoplasia (GTN)
Time frame: 1 year
Outcome will be measured by determining the proportion of eligible patients who consent to randomisation and the proportion of patients randomised to the intervention arm who complete protocol treatments. From this, it can be gauged how feasible it would be to open and recruit to a large scale more definitive study on using pembrolizumab in a neoadjuvant setting in GTN.
2 secondary outcomes
To assess the rate of surgical cure with and without pembrolizumab.
Time frame: 1 year
To assess the safety of a single dose of pembrolizumab prior to second evacuation versus second evacuation alone.
Time frame: 12 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Apr 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Philip Badman contact
Ehsan Ghorani study chair
Imperial College London University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Pembrolizumab in people with Gestational Trophoblastic Disease and Gestational Trophoblastic Neoplasia, run by Imperial College London at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 17 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Aaron Clarke (02033117740, aeclarke@ic.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To determine the feasibility of conducting a definitive study of neoadjuvant pembrolizumab prior to second evacuation of low risk postmolar gestational trophoblastic neoplasia (GTN) (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Apr 2024.