RESOLVE Trial Coordinating Centre
Imperial Clinical Trials Unit – (ICTU-Ca)
Cancer Research UK Convergence Science Centre
Department of Surgery and Cancer
Imperial College London
5th Floor Roderic Hill Building,
South Kensington Campus
Prince Consort Road,
London, SW7 2AZ
Email: RESOLVE@imperial.ac.uk
A feasibility window study of pembrolizumab prior to second evacuation for post-molar gestational trophoblastic neoplasia
Trial Aim:
a) To find out whether it is possible and safe to give pembrolizumab (an immunotherapy treatment) before the second procedure to remove the remaining tissue in patients with low-risk post-molar GTN, and
b) To collect tissue and blood to better understand the mechanisms of immune evasion and immunotherapy sensitivity in this disease
Design
A randomised open-label feasibility study of single dosed pembrolizumab prior to second evacuation for patients with post-molar Gestational Trophoblastic Neoplasia (GTN).
After the surgery has been performed, trial participants will be followed for a maximum period of 12 months post evacuation to review human chorionic gonadotropin (hCG) levels and monitor for further recurrence.
NCT05635344
ISRCTN86152317
Trial Documents
Centres:
Eligible patients with low-risk post-molar gestational trophoblastic neoplasia (GTN) will be recruited from the following centres:
If you wish to take part, please speak to your oncologist.
| Trial Locations | Investigator |
|---|---|
| Charing Cross Hospital in London | Dr Ehsan Ghorani |
| Weston Park Hospital in Sheffield (opening soon) | Prof Matthew Winter |
Trial background and previous research:
During pregnancy, the placenta grows to feed the baby. In few cases, cells of the placenta do not develop as they should and give rise to a pre-cancer called a molar pregnancy or mole which cannot grow into baby and must be removed. The standard treatment is a minor surgical procedure called an evacuation to gently clear the abnormal tissue from the womb. While most people heal completely after one procedure, the abnormal cells do not completely clear out or continue to grow in about 10% to 15% cases. If this happens, doctors will classify it as a type of cancer called Gestational Trophoblastic Neoplasia (GTN) which needs further medical care to cure it.
For most low-risk patients, chemotherapy is usually offered but this is time consuming, involves lots of visits and has side effects. An alternative is second surgery, which is reported to be successful in about 40% of cases.
The addition of pembrolizumab works by activating the immune system to fight the cancer and is a very powerful treatment in women with more advanced GTN who have become resistant to chemotherapy, curing about 75% of patients. An advantage of pembrolizumab is that it seems to be well tolerated. In about 60 women who have been treated around the world, we have seen an exceptionally low rate of severe side effects over many months of treatment.
Finally, in other cancer types, pembrolizumab is sometimes given before surgery and has proven to be very effective when given in this way.
We want to determine if giving pembrolizumab before second surgery will make the surgery more effective at curing the disease. If this works, it would mean patients can avoid chemotherapy and potentially complete their treatment much more quickly and with fewer side effects, meaning they can get back to normal faster.
Size of Trial
The study will include 20 patients. They will be randomly divided into two groups, with 10 patients in each group.
Study info
- Age ≥18yrs
- Postmolar GTN defined as recurrence or persistence of histologically confirmed CHM after primary surgical evacuation with no intervening treatment; along with plateau or rising human chorionic gonadotropin (hCG) level.
- HCG meeting the criteria of one of the following two groups; Group 1: hCG ≥ 1000 and ≤ 20,000 IU/L. Group 2: hCG > 20,000 IU/L & ≤ 50,000 IU/L and hCG not rising more than 2000 units/day across at least 2 samples taken within the last 1-2 weeks (with the latest sample taken as part of screening bloods).
- Low risk disease as defined by the Federation of Obstetrics and Gynaecology (FIGO) 2000 risk scoring criteria (score of 6 or less)
- No metastatic disease on chest X-ray
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- Presence of disease in uterine cavity
Adequate organ function as defined in the following: - Adequate bone marrow function measured within 28 days prior to administration of study treatment as defined below: Absolute granulocyte count ≥ 1.5 x 109/L ; Platelet count ≥ 100 x 109/L ; Haemoglobin ≥ 9.0 g/dL (may have been blood transfused)
- Adequate renal function: Calculated creatinine clearance ≥ 30 ml/min according to the Cockcroft-Gault formula; as well as adequate hepatic function: Serum bilirubin ≤ 1.5 x Upper normal limit (ULN) and AST/ALT ≤ 2.5 X ULN
- 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 tumour (PSTT) or epithelioid trophoblastic tumour (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.
- 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.
- 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 (e.g., 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.
- History of active Bacillus Tuberculosis (TB).
- 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.
- Hypersensitivity to pembrolizumab
Funding:
This project was funded by Imperial BRC, The Cancer Treatment and Research Trust Charity, and Cancer Research UK.
