Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Rare Diseases

Gestational Trophoblastic Disease

Trophoblastic Neoplasms

Hydatidiform Mole

Choriocarcinoma

Nevus

Hydatidiform Mole, Invasive

Trophoblastic Tumor, Placental Site

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Pregnancy Complications

Pregnancy Complications, Neoplastic

Urogenital Diseases

Female Urogenital Diseases

Female Urogenital Diseases and Pregnancy Complications

François Golfier, Pr

Touria Hajri

The French Gestational Trophoblastic Disease (GTD) centre has been set up and active by registering, monitoring and treating women with GTD since november 1999. The aim is to improve the management of trophoblastic disease in France.

About 850 new cases are registered each year and 140 women treated, mostly with chemotherapy and surgery.

The center works as follow, based on a multidisciplinary approach. The policy is that patient remains followed by her local physician, but can be seen and treated in the Center at demand and that the registry is done on a voluntary basis.

Each administrative french area has a local expert team (oncologist and gynaecologist) who is able to look after the patients with the help of the national reference center physicians based in Lyon.

* Once a doctor discovers a molar pregnancy, he contacts the center, with the agreement of his patient, for an opinion, an advice or simply to report the case.
* The center sends to the doctor the informed consent form to be signed by the patient, a registering form and information about pathology for patient and physician, and first guidelines based on initial pathology report.

The patient remains followed by her gynecologist, who stays her first interlocutor throughout the whole process and she goes to her local laboratory for hCG monitoring;

* A letter is sent to the initial pathology laboratory that originally carried the diagnosis of molar pregnancy to require slide sending to the pathologist referral center (9 experts with a specific pathologist national network) that centrally review initial diagnosis.
* In the mean time, the data manager collects weekly hCG values to establish a follow-up chart. The physician is regularly informed by mail of the hCG evolution.
* The local physician is contacted in case of modification of the diagnosis by the pathologist expert. The center informs him about length and monitoring methodology.
* Emails or letters are sent at each step of the management (at inclusion, at hCG negativation, and at the end of hCG follow-up).
* In case of abnormal hCG evolution (raise, plateauing or positivity at 6 months,) or if a neoplasia is anatomopathologically diagnosed (choriocarcinoma, PSTT or ETT), physician is immediately contacted by phone or email by referent gynaecologist. A complete work up including pelvic US with Doppler, pelvic MRI, thoraco-abdominal CT-scan with chest radiography if pulmonary nodules are present and brain MRI, is planned to determine the adequate treatment.

Very briefly, based on imaging results, FIGO stade and score are calculated to determine the risk. In case of low-risk, a monochemotherapy is settled, while a polychemotherapy is started in case of high-risk disease.

The investigators have developped specific expertise at key levels of diagnosis, management, follow-up, fertility preservation and treatment.

Assignments :

* Registration and monitoring post diagnosis of complete or partial molar pregnancy, choriocarcinoma,PSTT, ETT, atypical placental site nodules
* Histopathological analysis and genetics services
* Measurement of human chorionic gonadotrophin (hCG) isoforms
* Complex gynaecological surgery

The French National Reference Centre of GTD

The French National Reference Centre of Gestational Trophoblastic Disease

trophoblastic deseases can be partial or complete molal pregnancy, choriocarcinoma, , placental site trophoblastic tumors (PSTT), epithelioid trophoblastic tumors (ETT), atypical placental site nodule.

Hospices Civils de Lyon

Symptoms and General Pathology

Recurrence

Gestational Trophoblastic Tumor

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Patients that are randomised onto this arm of the study will be treated by second evacuation ALONE.

Patients that are randomised onto this arm will be given a single dose of Pembrolizumab in a neoadjuvant setting followed by second evacuation

Single dose 200mg dose of Pembrolizumab given intravenously

Aaron Clarke

Philip Badman

Dr Ghorani

Ehsan Ghorani

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.

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

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.

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.

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).

Cancer Research UK

Imperial College London

Vasodilator Agents

Nitroglycerin

Letrozole

Aromatase Inhibitors

Enzyme Inhibitors

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Hormones

Hormone Antagonists

Patients with complete mole treated by evacuation of using suction curettage followed by conservative follow up

Patients with complete mole treated by evacuation of using suction curettage followed by 5mg daily letrozole for 10 days followed by conservative follow up

both groups underwent complete mole evacuation using suction curettage.

Suction evacuation

Group II Patients received 5mg(2tablets 2.5gm) daily letrozole for 10 days after complete mole evacuation

Letrozole tablets

Mohamed A Alabiad, MD

Prophylactic use of aromatase inhibitor is effective in decreasing the incidence of Gestational Trophoblastic Neoplasia (GTN) in patients with complete hydatidiform mole (CHM)

Management of hydatidiform mole is usually evacuation followed by β-hcg surveillance to early detect cases of GTN . The risk of developing GTN is reported to be 16% to 20% in women with CHM . GTN is a potentially life-threatening malignancy but has an excellent cure rate. Trials were conducted to assess the role of prophylactic chemotherapy to prevent the development of GTN. In addition to their side effects, a meta-analysis concluded that there is insufficient evidence to support the use of prophylactic chemotherapy in clinical practice. Third-generation aromatase inhibitors such as letrozole have been shown to successfully block estrogen production in women of reproductive age. Their safety, high tolerability, low cost, and associated minimal adverse effects have all been established over several decades of clinical use and recently used successfully alone in the medical treatment of ectopic pregnancy making marked degenerative effects on the placenta.

The study hypothesizes that by inhibiting the estrogen synthetase (the aromatase enzyme) progesterone would not exert its physiological role in maintaining early pregnancy including complete hydatidiform mole. Thus, using a prophylactic aromatase inhibitor after CHM may have a role in the prevention of GTN and more effective clearance of β-hcg.

Rational GTN is a potentially life-threatening malignancy. The risk of progression of CHM to GTN is 20%. Prophylactic use of aromatase inhibitor may decrease the incidence of GTN.

Research question:

Is prophylactic use of aromatase inhibitor effective in decreasing the incidence of GTN in patients with CHM

Hypothesis Prophylactic use of aromatase inhibitor is effective in decreasing the incidence of GTN in patients with CHM

Aim of this work The study aims at figuring out whether prophylactic use of aromatase inhibitor is effective in decreasing the incidence of GTN in patients with CHM.

OBJECTIVES

* To assess the incidence of GTN after the evacuation of CHM without prophylactic use of aromatase inhibitor.
* To assess the incidence of GTN after the evacuation of CHM without prophylactic use of aromatase inhibitor.
* To assess the side effects of aromatase inhibitor when used as a prophylaxis against GTN development in CHM cases.

PATIENTS AND METHODS

Technical design:

* Setting: Department of Obstetrics and Gynecology
* Sample size: 200 patients diagnosed to have CHM by ultrasound and confirmed by histopathological examination.

Operational design:

* Type of the study: a randomized controlled trial.
* Steps of performance and techniques that will be used

women included in the study will be subjected to the following

Preoperative

1. Complete history taking.
2. General and abdominal examination.
3. Routine preoperative laboratory investigations.
4. Ultrasound to diagnose complete hydatidiform mole.
5. Measurement of β-hcg level. Intraoperative

   * Evacuation of CHM using Suction curettage.
   * Tissues obtained during an evacuation will be sent for histological assessment. Post-operative
   * Women will be randomized classified into two groups
   * Control group I: Conservative follow up
   * Prophylactic letrozole group II 5-mg Letrozole will be administered as two 2.5-mg tablets every day for 10 days.
   * All Patients will receive instruction to return for β-hcg follow up which will be done weekly till complete resolution then monthly for 6 months.
   * Participants will be advised to receive contraception during the follow-up period.
   * The patients who will develop GTN in either group will be picked up and the incidence of GTN will be calculated in each group.

Letrozole as a Prophylaxis From GTN for Complete Mole Patients

The Prophylactic Role of Aromatase Inhibitor Letrozole in Decreasing the Incidence of Gestational Trophoblastic Neoplasia in Patients With Complete Hydatidiform Mole

A quantitative human chorionic gonadotropin

Zagazig University

Principal Investigator

Antirheumatic Agents

Dermatologic Agents

Reproductive Control Agents

Anti-Infective Agents

Methotrexate

Dactinomycin

Regimen: Methotrexate 0.4mg/(kg·d) intramuscularly (IM) on days 1-5. If 10-fold fall of hCG achieved 18 days after treatment completion, success of primary single-course chemotherapy was defined and further treatment was withheld; otherwise, failure was defined and the patient was referred to multi-course chemotherapy. During the period of observation for those with success, if the level of hCG became stationary for at least 3 weeks or rose again, the patient was also referred to multi-course chemotherapy. Additional consolidation chemotherapy with 1-3 courses was given for those who achieved CR by multi-course chemotherapy, but not by single-course regimen.

Regimen: dactinomycin d 0.6mg/m2, IV, on day1, 2; methotrexate 100mg/m2, IV, on day1 (after Act-d); methotrexate 200mg/m2, IVgtt, on day1 (after methotrexate, 500ml NS, \>4h).

If 10-fold fall of hCG achieved 18 days after treatment completion, success of primary single-course chemotherapy was defined and further treatment was withheld; otherwise, failure was defined and the patient was referred to multi-course chemotherapy. During the period of observation for those with success, if the level of hCG became stationary for at least 3 weeks or rose again, the patient was also referred to multi-course chemotherapy. Additional consolidation chemotherapy with 1-3 courses was given for those who achieved CR by multi-course chemotherapy, but not by single-course regimen.

Regimen: methotrexate 0.4mg/(kg·d) intramuscularly (IM) on days 1-5, 2-week intervals. Patients continue on treatment until 1 beta HCG titer is below the institutional normal. Patients then receive at least 1 additional consolidation treatment.

After treatment, all the patients were asked for contraception with condom or oral contraception. Regular hCG surveillance, once a month for 3 consecutive months and once every 3 months for 2 years, was performed. During follow-up period, pelvic ultrasound and pulmonary X ray or CT scan were conducted if needed.

MTX 0.4mg/(kg·d) intramuscularly (IM) on days 1-5

MTX 1

MTX 100mg/m(2), IV, on day1 (after Act-d); MTX 200mg/m(2), IVgtt, on day1 (after MTX, 500ml NS, \>4h)

MTX 2

Act-d

Xing Xie, MD, PhD

The investigators conducted a trial to determine whether methotrexate or methotrexate/dactinomycin single-course treatment work well as multiple courses of single methotrexate chemotherapy in low-risk gestational trophoblastic neoplasia. It is not yet known whether single-course of chemotherapy is as the same effectiveness as multicourse.

Methotrexate Single-dose Treatment and Methotrexate/Actinomycin-D Single-dose Treatment in Low-Risk Gestational Trophoblastic Neoplasia

A Multicenter, Prospective, Randomized Trial of Methotrexate Single-dose Treatment and Methotrexate/Actinomycin-D Single-dose Treatment in Low-Risk Gestational Trophoblastic Neoplasia

Zhejiang University

Huazhong University of Science and Technology

Shandong University

Ding Ma

Director of the department of Obstetrics and Gynecology, Tongji Hospital

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Diseases

Genital Diseases, Female

Genital Diseases

30 patients survived GTD post treatment for 0 - 5 years.

30 patients survived GTD post treatment 6 - 10+ years.

A patient questionnaire, which includes validated instruments. Data collection methods are as follows:

* In person at the medical appointment
* Over the telephone
* Mailed with self-addressed return envelope and prepaid postage
* E-mailed and returned by e-mail, fax or self-addressed envelope and pre-paid postage

questionnaire

Elizabeth Jewell, MD

The purpose of this study is to collect information on the effects of treatment for gestational trophoblastic disease (GTD). We plan to use the findings from this study to better understand GTD survivors' health and quality of life.

We would like to know more about the health, quality of life and pregnancies of women treated for GTD. This information will be used to try and improve the treatments for women who have this disease.

A Global Assessment of Medical, Emotional and Reproductive Concerns in Gestational Trophoblastic Disease Survivors

Memorial Sloan Kettering Cancer Center

Gland and Hormone Related Diseases

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Uterine Cervical Neoplasms

Vaginal Neoplasms

Vulvar Neoplasms

Endometrial Neoplasms

Vulvar Diseases

Vaginal Diseases

Ovarian Cancer

Ovarian Epithelial Cancer

Vaginal Cancer

Vulvar Cancer

Participants are provided with a question prompt list

Participants will not be provided with the question prompt list

Participants are randomized and will receive the ASQ-GYO prompt list within 2 weeks prior to their new patient appointment with the gynecology oncology physician.

Administration of the ASk Questions in GYnecologic Oncology (ASQ-GYO) Question Prompt List

Ira Winer, MD PhD

Elizabeth Johns, MD MS

Ira Winer, M.D. PhD

Elizabeth Johns

Susan Eggly, PhD

Larrissa Mattei, MD

Anna Gotschlich, PhD

Wei Chen, PhD

Sam Robinson, PhD

The goal of this clinical trial is to determine the effectiveness of the ASk Questions in GYnecologic Oncology question prompt list (ASQ-GYO QPL) at improving patient self-efficacy, distress, physician trust, and knowledge compared to usual care during new patient gynecologic oncology visits. Also to determine the acceptability of the ASQ-GYO QPL with new gynecologic oncology patients.

* Potential participants who are scheduled for a new patient appointment will be contacted via phone or email to determine if they are interested in participating.
* If a participant is interested, they will choose their preferred method of consenting (phone, email, or in person) and if they would like to complete the pre-visit survey now or at a later time prior to their appointment
* If consented, all participants will be provided with the pre-survey questionnaire. If eligible, participants will then be randomized to usual care or the intervention (ASk Questions in GYnecologic Oncology question prompt list (ASQ-GYO QPL)
* If randomized to receive the ASQ-QYO QPL, they will be emailed this document and given a paper copy of the ASQ-GYO QPL in the waiting room prior to their visit to ensure they have received the intervention.
* Directly after the participant's visit, all participants will be asked to complete the post-visit survey on a tablet in the clinic waiting room, or via a secure link in an email within 1 week of the appointment.
* After completion of the post-visit survey and within one month of their visit, participants who were not randomized to receive the ASQ-GYO QPL will be sent the ASQ-GYO QPL via email so that they may also have access to this resource.

ASk Questions in GYnecologic Oncology (ASQ-GYO)

ASk Questions in GYnecologic Oncology (ASQ-GYO): A Randomized Controlled Trial of a Question Prompt List Communication Intervention in Outpatient Gynecologic Oncology Clinics

The Perceived Efficacy in Patient-Provider Interactions (PEPPI) instrument is a validated, 20-item, 5-point Likert scale tool designed to measure patient's self-efficacy in obtaining medical information and attention to their medical concerns from physicians.

The NCCN Distress Thermometer is a one-question, 11-point Likert scale for patient-reported distress in the past week including today

The Trust in a Physician score is a validated, 5-point Likert scale with higher scores indicating more trust. The metric addresses generic physician trust prior to the visit, and trust in the specific physician the patient saw during their visit for after the visit

The Knowledge Screen is a 10-item, 5-point Likert scale, investigator-developed set of questions designed to elicit understanding of the contents of the Question Prompt List with higher scores indicating more understanding.

This is a 15-item investigator-developed set of questions with 7 items utilizing a 5-point Likert scale and 8 items utilizing binary yes/no questions designed to elicit the acceptability of the Question Prompt List among the patients in the intervention group.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
The French National Reference Centre of GTD	NCT02892877	Neoplasm, Troph... Gestational Tro... Hydatidiform Mo... Hydatidiform Mo...		-	Hospices Civils de Lyon
A Feasibility Window Study of Pembrolizumab Prior to Second Evacuation for Post-molar Gestational Trophoblastic Neoplasia	NCT05635344	Gestational Tro... Gestational Tro... Gestational Tro...	Pembrolizumab	18 Years -	Imperial College London
A Feasibility Window Study of Pembrolizumab Prior to Second Evacuation for Post-molar Gestational Trophoblastic Neoplasia	NCT05635344	Gestational Tro... Gestational Tro... Gestational Tro...	Pembrolizumab	18 Years -	Imperial College London
Letrozole as a Prophylaxis From GTN for Complete Mole Patients	NCT05203562	Gestational Tro...	Suction evacuat... Letrozole table...	20 Years - 40 Years	Zagazig University
Methotrexate Single-dose Treatment and Methotrexate/Actinomycin-D Single-dose Treatment in Low-Risk Gestational Trophoblastic Neoplasia	NCT01823315	Gestational Tro... Gestational Tro... Gestational Tro... Gestational Tro...	MTX 1 MTX 2 Act-d	18 Years - 60 Years	Huazhong University of Science and Technology
A Global Assessment of Medical, Emotional and Reproductive Concerns in Gestational Trophoblastic Disease Survivors	NCT00706875	Uterine Cancer Cervix Uteri No... Gestational Tro...	questionnaire questionnaire	18 Years - 60 Years	Memorial Sloan Kettering Cancer Center
A Global Assessment of Medical, Emotional and Reproductive Concerns in Gestational Trophoblastic Disease Survivors	NCT00706875	Uterine Cancer Cervix Uteri No... Gestational Tro...	questionnaire questionnaire	18 Years - 60 Years	Memorial Sloan Kettering Cancer Center
Letrozole as a Prophylaxis From GTN for Complete Mole Patients	NCT05203562	Gestational Tro...	Suction evacuat... Letrozole table...	20 Years - 40 Years	Zagazig University
ASk Questions in GYnecologic Oncology (ASQ-GYO)	NCT06339827	Ovarian Cancer Endometrial Can... Cervical Cancer Vulvar Cancer Vaginal Cancer Gestational Tro...	Administration ...	18 Years -	Barbara Ann Karmanos Cancer Institute

Spots Global Cancer Trial Database for gestational trophoblastic disease