RecruitingPhase 1/2

Avelumab and Methotrexate in in Low-risk Gestational Trophoblastic Neoplasias as First Line Treatment

France26 participantsStarted 2020-02-12

Plain-language summary

Gestational trophoblastic neoplasias (GTN) are characterized by the persistence of elevated hCG titers after complete uterine evacuation of a partial hydatidiform mole (PHM) or a complete hydatidiform mole. Low-risk GTN patients (FIGO score ≤ 6) are commonly treated with single agent treatment (methotrexate or actinomycin-D) The cure rate, assessed by hCG normalization, is obtained in 65 to 75% of patients with these agents GTN patients with resistance to these treatments are treated with another single agent drug or polychemotherapy regimens, such as EMA-CO or BEP regimen. Chemotherapy standard regimens are old and toxic for these young lady patients, with potential long term effects detrimental for further maternity and quality of life There is a strong rational for investigating the anti-PDL1 monoclonal antibody avelumab in chemoresistant GTN patients. Several elements suggest that the normal pregnancy immune tolerance is "hijacked" by GTN cell for proliferating : * Spontaneous regressions of metastastic GTN are regularly observed, thereby the role of immune system for rejecting GTN cells. * Strong and constant overexpression of PDL1 and NK cells has been found in all subtypes and settings of GTN tumors from French reference gestational trophoblastic center. * Complete and durable responses to pembrolizumab were reported in 3 patients with multi-chemoresistant GTN in United Kingdom. * Three cases of hCG normalization with avelumab in 6 patients with chemo-resistant GTN enrolled in TROPHIMMUN cohort A (resistant to a mono-chemotherapy). * Cytotoxicity of avelumab is mediated through antibody dependent cell cytotoxicity (ADCC) by NK cells.

Who can participate

Age range18 Years

SexFEMALE

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AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion Criteria: * \- Woman older than 18 years * Low-risk gestational trophoblastic neoplasia according to FIGO score (FIGO score ≤ 6) with indication of methotrexate as first line treatment * Patients with Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 * Patients with adequate bone marrow function measured within 28 days prior to administration of study treatment as defined below * Absolute granulocyte count ≥ 1.5 x 10 9 /L * Platelet count ≥ 100 x 10 9 /L * Haemoglobin ≥ 9.0 g/dL (may have been blood transfused) * Patients with adequate renal function: \* Calculated creatinine clearance ≥ 30 ml/min according to the Cockcroft-Gault formula (or local institutional standard method) * Patients with adequate hepatic function \*Serum bilirubin ≤ 1.5 x UNL and AST/ALT ≤ 2.5 X UNL (≤ 5 X UNL for patients with liver metastases) * Patients must have a life expectancy ≥ 16 weeks * Confirmation of non-childbearing status for women of childbearing potential. An evolutive pregnancy can be ruled out in the following cases: * in case of a previous hysterectomy * if serum hCG level ≥ 2 000 IU/L and no intra or extra-uterine gestational sac is detected on pelvic ultrasound * if serum hCG level \< 2 000 IU/L on a first measurement and serum hCG increases \<100% on a second measurement performed 3 days later. * Highly effective contraception if the risk of conception exists. (Note: The effects of the trial drug on the developing human fetus are unknown;…

What they're measuring

Incidence of Dose limiting toxicities of methotrexate and avelumab combination in low-risk GTN patients as first line.

Timeframe: treatment duration 3 months (median estimation)

Rate of patients with successful normalization of hCG

Timeframe: treatment duration 3 months (median estimation)

Trial details

NCT IDNCT04396223

SponsorHospices Civils de Lyon

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2025-04-12

Contact for this trial

Benoit YOU, MD

33 4 78 864 318 benoit.you@chu-lyon.fr