Chemoresistance of Trophoblastic Tumors (PrediCTTro)

Prediction of Chemoresistance in Patients Treated for Gestational Trophoblastic Tumors

Gestational trophoblastic tumors are characterized by their development from placental tissue and their high invasive and metastatic potential. These are rare tumors (1/50 000 pregnancies) affecting young women for whom conservative fertility treatments are preferred. The therapeutic strategy is based on a chemotherapy whose choice of protocol is based on a clinico-biological score, FIGO score, which includes tumor size, gonadotropic chorionic hormone level used as quantitative tumor marker, number and localization. metastases. A FIGO score ≤6 allows the use of monochemotherapy (methotrexate) with a 5-year survival of approximately 99.7%. Scores of 7 to 12 and ≥13 require multidrug therapy (EMA-CO) and are associated with 5-year survival of 95.1% and 61.6%, respectively.

The chemotherapies currently used for the treatment of trophoblastic tumors have been described between the 1950s (methotrexate) and the 1980s (EMA-CO) and have a well documented toxicity regarding the risk of secondary tumors, early menopause or even death by toxicity. .

To date, apart from the FIGO score, there is no predictor of resistance to chemotherapy in gestational trophoblastic tumors. However, among patients with a FIGO score ≤6 and receiving methotrexate in the first line, 9 to 46% will have a resistance and require a second line of treatment. Similarly, if the score is ≥7, 10 to 30% of patients receiving EMA-CO will require at least a second line of multidrug therapy.

The hypothesis of PrediCTTro study is that tissue samples of gestational choriocarcinoma present a transcriptomic profile associated with the risk of further resistance to single or multiagent chemotherapy.

The objective of PrediCTTro is to identify a transcriptomic signature able to predict resistance to single or multiagent chemotherapy.

Study Overview

• Status: Unknown
• Conditions: Trophoblastic Tumor
• Intervention / Treatment: Other: chemoresistance signature

• Study Type: Observational
• Enrollment (Anticipated): 72

Contacts and Locations

• Study Contact: Name: Pierre-Adrien BOLZE, Dr; Phone Number: +33 04 78 86 56 40; Email: pierre-adrien.bolze@chu-lyon.fr
• Study Contact Backup: Name: François GOLFIER, Pr; Phone Number: +33 04 78 86 66 78; Email: francois.golfier@chu-lyon.fr

Study Locations

• France
  • Pierre-Bénite, France, 69495
    • Centre Français de Référence des Maladies Trophoblastiques
    • Contact: Pierre-Adrien BOLZE, Dr; Phone Number: +33 04 78 86 56 40; Email: pierre-adrien.bolze@chu-lyon.fr
    • Contact: François GOLFIER, Pr; Phone Number: +33 04 78 86 66 78; Email: francois.golfier@chu-lyon.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

Patients diagnosed with gestational trophoblastic tumors

Description

Inclusion Criteria:

• confirmed gestational trophoblastic tumor histology
• hCG follow-up of at least 12 months after hCG normalization
• registration in the French Reference Center for Trophoblastic Diseases

Exclusion Criteria:

• tissue specimen (block/biopsy) not available
• degraded quality of tissue sample not compatible with transcriptome analysis (>20% of necrosis)

Study Plan

How is the study designed?

Number of groups / cohorts

6

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
methotrexate sensitive; patients with gestational choriocarcinoma cured with methotrexate alone	Other: chemoresistance signature; to study the predictive value of a tissue transcriptomic profile (=chemoresistance signature) in the chemoresistance to single or multiagent chemotherapy
methotrexate resistant; patients with gestational choriocarcinoma not cured with methotrexate alone	Other: chemoresistance signature; to study the predictive value of a tissue transcriptomic profile (=chemoresistance signature) in the chemoresistance to single or multiagent chemotherapy
polychemotherapy sensitive; patients with gestational choriocarcinoma cured with polychemotherapy	Other: chemoresistance signature; to study the predictive value of a tissue transcriptomic profile (=chemoresistance signature) in the chemoresistance to single or multiagent chemotherapy
polychemotherapy resistant; patients with gestational choriocarcinoma not cured with polychemotherapy	Other: chemoresistance signature; to study the predictive value of a tissue transcriptomic profile (=chemoresistance signature) in the chemoresistance to single or multiagent chemotherapy
hydatidiform moles without malignant transformation; patients treated for hydatidiform moles but who did not turn into trophoblastic tumors (=controls)	Other: chemoresistance signature; to study the predictive value of a tissue transcriptomic profile (=chemoresistance signature) in the chemoresistance to single or multiagent chemotherapy
placental site trophoblastic tumors; patients with placental site trophoblastic tumors not cured with polychemotherapy	Other: chemoresistance signature; to study the predictive value of a tissue transcriptomic profile (=chemoresistance signature) in the chemoresistance to single or multiagent chemotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Transcription profile associated with the resistance to chemotherapy	The expression level of 800 genes involved in oncogenesis canonical pathways and immune tolerance will be assessed and correlated with the resistance to single or multiagent chemotherapy.	10 months

Collaborators and Investigators

• Sponsor: Hospices Civils de Lyon

Study record dates

Study Major Dates

• Study Start (Anticipated): April 1, 2018
• Primary Completion (Anticipated): October 1, 2018
• Study Completion (Anticipated): December 1, 2018

Study Registration Dates

• First Submitted: March 29, 2018
• First Submitted That Met QC Criteria: March 29, 2018
• First Posted (Actual): April 5, 2018

Study Record Updates

• Last Update Posted (Actual): April 5, 2018
• Last Update Submitted That Met QC Criteria: March 29, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Germ Cell and Embryonal; Pregnancy Complications; Pregnancy Complications, Neoplastic; Trophoblastic Neoplasms
• Other Study ID Numbers: 69HCL16_807

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No