Using Pembrolizumab before surgery for recurrent gestational trophoblastic disease

A Feasibility Window Study of Pembrolizumab Prior to Second Evacuation for Post-molar Gestational Trophoblastic Neoplasia

This study is testing whether giving the immunotherapy drug Pembrolizumab before surgery can help patients with recurrent gestational trophoblastic disease do better and avoid chemotherapy.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years and up
• Sex: Female
• Sponsor: Imperial College London (Academic / other)
• Drugs / interventions: prednisone, Pembrolizumab, chemotherapy, Immunotherapy
• Locations: 1 site (London)
• Trial ID: NCT05635344 on ClinicalTrials.gov

What this trial studies

This study evaluates the feasibility of administering Pembrolizumab, an immunotherapy drug, prior to a second surgical evacuation in patients with recurrent gestational trophoblastic neoplasia (GTN). The aim is to assess whether this approach can improve outcomes for patients who have not been cured by initial surgery. The study focuses on patients with specific criteria, including rising or plateaued human chorionic gonadotropin (hCG) levels and low-risk disease as defined by FIGO scoring. By exploring this alternative treatment strategy, the study seeks to reduce the need for chemotherapy and its associated side effects.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 and older with recurrent postmolar GTN and specific hCG levels.

Not a fit: Patients with metastatic disease or those with high-risk GTD may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a less harmful treatment option for patients with recurrent GTD, potentially improving their quality of life.

How similar studies have performed: While the use of Pembrolizumab in this context is novel, similar immunotherapy approaches have shown promise in treating other types of cancer.

Eligibility criteria

Inclusion Criteria:

1. Written informed consent prior to initiation of any study procedures and willingness and ability to comply with the study schedule.
2. Age ≥18yrs
3. Postmolar GTN defined as recurrence or persistence of histologically confirmed CHM after primary surgical evacuation with no intervening treatment.
4. 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.
5. hCG under 20,000 IU/L
6. Low risk disease as defined by the Federation of Obstetrics and Gynecology (FIGO) 2000 risk scoring criteria (score of 6 or less)
7. No metastatic disease on chest X-ray.
8. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
9. Disease present within the uterine cavity not within 5mm of the serosal surface.
10. 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
11. 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

Exclusion Criteria:

1. 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.
2. Patients with histologically confirmed choriocarcinoma, placental site trophoblastic tumor (PSTT) or epithelioid trophoblastic tumor (ETT) on the first curettage.
3. Pregnant women.
4. Uncontrolled vaginal bleeding.
5. 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.
6. 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.
7. 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.
8. History of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
9. History of Human Immunodeficiency Virus (HIV) infection.
10. 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.
11. History of active TB (Bacillus Tuberculosis).
12. 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.
13. History of allogenic tissue/solid organ transplant.

Where this trial is running

London

• Imperial College Healthcare NHS Trust — London, United Kingdom (Recruiting)

Study contacts

• Study coordinator: Aaron Clarke

Conditions Gestational Trophoblastic Disease; Gestational Trophoblastic Neoplasia; Gestational Trophoblastic Tumor, Recurrent