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A Multicenter, Open-label, Randomized, Phase 3 Trial to Compare the Efficacy and Safety of Lenvatinib in Combination With Pembrolizumab Versus Treatment of Physician's Choice in Participants With Advanced Endometrial Cancer - MK-3475-775 (Keynote-775)

Studio Clinico

Patologia: Tumori dell’utero

Osservazionale-Sperimentale: Sperimentale

Monocentrico-Multicentrico: Multicentrico

Randomizzato: 

Fase di studio: III

Richiesta mandatoria di tessuto: 

Linee di trattamento: Seconda linea

Criteri di inclusione: 

1. Has a histologically confirmed diagnosis of endometrial carcinoma (EC)
2. Documented evidence of advanced, recurrent or metastatic EC.
3. Has radiographic evidence of disease progression after 1 prior systemic, platinum-based chemotherapy regimen for EC. Participants may have received up to 1 additional line of platinum-based chemotherapy if given in the neoadjuvant or adjuvant treatment setting.
    Note: There is no restriction regarding prior hormonal therapy.

4. Has historical or fresh tumor biopsy specimen for determination of mismatch repair (MMR) status.
5. Has at least 1 measurable target lesion according to Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 and confirmed by Blinded Independent Central Review BICR.
6. Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days of starting study treatment.
7. Is not pregnant, breastfeeding, and agrees to use a highly effective method of contraception during the treatment period and for at least 120 days (for participants treated with lenvatinib plus pembrolizumab) or at least 180 days (for participants treated with treatment of physician's choice [TPC]) after the last dose of study treatment.

Criteri di esclusione: 

1. Has carcinosarcoma (malignant mixed mullerian tumor), endometrial leiomyosarcoma and endometrial stromal sarcomas.
2. Has unstable central nervous system (CNS) metastases.
3. Has active malignancy (except for endometrial cancer, definitively treated in-situ carcinomas [e.g. breast, cervix, bladder], or basal or squamous cell carcinoma of the skin) within 24 months of study start.
4. Has gastrointestinal malabsorption, gastrointestinal anastomosis, or any other condition that might affect the absorption of lenvatinib.
5. Has a pre-existing greater than or equal (>=) Grade 3 gastrointestinal or non-gastrointestinal fistula.
6. Has radiographic evidence of major blood vessel invasion/infiltration.
7. Has clinically significant hemoptysis or tumor bleeding within 2 weeks prior to the first dose of study treatment.
8. Has a history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction, cerebrovascular accident (CVA) stroke, or cardiac arrhythmia associated with hemodynamic instability within 12 months of the first dose of study treatment.
9. Has an active infection requiring systemic treatment.
10. Has not recovered adequately from any toxicity and/or complications from major surgery prior to starting therapy.
11. Is positive for Human Immunodeficiency Virus (HIV).
12. Has active Hepatitis B or C.
13. Has a history of (non-infectious) pneumonitis that required treatment with steroids, or has current pneumonitis.
14. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study.
15. Has a diagnosis of immunodeficiency or is 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 study start -Has an active autoimmune disease (with the exception of psoriasis) that has required systemic treatment in the past 2 years.
16. Is pregnant or breastfeeding.
17. Has had an allogenic tissue/solid organ transplant.
18. Has received >1 prior systemic chemotherapy regimen (other than adjuvant or neoadjuvant) for Endometrial Cancer. Participants may receive up to 2 regimens of platinum-based chemotherapy in total, as long as one is given in the neoadjuvant or adjuvant treatment setting.
19. Has received prior anticancer treatment within 28 days of study start. All acute toxicities related to prior treatments must be resolved to Grade ≤1, except for alopecia and Grade ≤2 peripheral neuropathy.
20. Has received prior treatment with any treatment targeting VEGF-directed angiogenesis, any anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
21. Has received prior treatment with an agent directed to a stimulatory or co-inhibitory T-cell receptor other than an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, and who has discontinued from that treatment due to a Grade 3 or higher immune-related adverse event.
22. Has received prior radiation therapy within 21 days of study start with the exception of palliative radiotherapy to bone lesions, which is allowed if completed 2 weeks of study start. Participants must have recovered from all radiation-related toxicities and/or complications prior to randomization.
23. Has received a live vaccine within 30 days of study start.
24. Has a known intolerance to study treatment (or any of the excipients).
25. Prior enrollment on a clinical study evaluating pembrolizumab and lenvatinib for endometrial carcinoma, regardless of treatment received.
26. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks of study start.
27. Participants with urine protein ≥1 gram (g)/24 hour.
28. Prolongation of corrected QT (QTc) interval to >480 milliseconds (ms).
29. Left ventricular ejection fraction (LVEF) below the institutional normal range as determined by multigated acquisition scan (MUGA) or echocardiogram (ECHO).

Trattamento sperimentale: 

Lenvatinib 20 mg + Pembrolizumab 200 mg

Trattamento di controllo: 

Treatment of Physician's Choice

Obiettivi primari dello studio: 

1. Progression Free Survival (PFS) [ Time Frame: Up to approximately 24 months ]
PFS is defined as the time from randomization to the first documented disease progression per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as determined by Blinded Independent Central Review (BICR) or death due to any cause, whichever occurred first.

2. Overall Survival (OS) [ Time Frame: Up to approximately 27 months ]
OS is defined as the time from date of randomization to date of death from any cause.

Centri partecipanti

Nord Italia

IRCCS - IRST
Via P. Maroncelli 40 - 47014 Meldola - FC

Riferimento: Dr. Ugo De Giorgi

 

IRCCS Istituto Nazionale dei Tumori
Via Venezian 1 - 20133 Milano - MI

Riferimento: Dr.ssa Domenica Lorusso
Email: domenica.lorusso@istitutotumori.mi.it

 

Ospedale San Raffaele di Milano
Via Olgettina 60 - 20132 Milano - MI

Riferimento: Dr.ssa Giorgia Mangili
Email: mangili.giorgia@hsr.it

 

Centro Italia

Fondazione Policlinico A. Gemelli
Largo Agostino Gemelli 8 - 00168 Roma - RM

Riferimento: Prof. Giovanni Scambia
Telefono: 0630156134
Email: giovanni.scambia@policlinicogemelli.it

 

Sud Italia e isole

A.O. per l’Emergenza Cannizzaro di Catania
Via Messina 829 - 95126 Catania - CT

Riferimento: Prof. Paolo Scollo

 

Istituto Nazionale Tumori IRCCS Fondazione Pascale
Via Mariano Semmola - 80131 Napoli - NA

Riferimento: Dr.ssa Carmela Pisano

Informazioni Generali

Protocollo

Numero di iscrizione a registro: 2017-004387-35

Data di inserimento: 11.02.2019

Promotore

Eisai Inc. (Collaborator: Merck Sharp & Dohme Corp)

CRO

/

Principal Investigator ITALIA

Fondazione Policlinico Universitario A. Gemell, Roma

Riferimento: Prof. Giovanni Scambia

Telefono: 0630156134

Email: giovanni.scambia@policlinicogemelli.it

Localita: Roma

 

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