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 Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
20
Single dose 200mg dose of Pembrolizumab given intravenously
Imperial College Healthcare NHS Trust
London, United Kingdom
RECRUITINGTo 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.
Time frame: 1 year
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.
Time frame: 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).
Time frame: 12 weeks
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