MK3475-B96 - A Phase 3, Randomized, Double-Blind Study of Pembrolizumab Versus Placebo in Combination With Paclitaxel With or Without Bevacizumab for the Treatment of Platinum-resistant Recurrent Ovarian Cancer (KEYNOTE-B96/ENGOT-ov65)

Studio Clinico

Patologia: Tumori dell’ovaio

Osservazionale-Sperimentale: Sperimentale

Monocentrico-Multicentrico: Multicentrico

Randomizzato: Sì

Fase di studio: III

Linee di trattamento: Prima linea, Seconda linea

Criteri di inclusione: 

• Has histologically confirmed epithelial ovarian, fallopian tube, or primary peritoneal carcinoma.
• Has received 1 or 2 prior lines of systemic therapy for ovarian cancer (OC), including at least 1 prior platinum-based therapy. Participants may have received a prior poly (ADP-ribose) polymerase inhibitor (PARPi), anti-PD-1/anti-PD-L1 therapy or bevacizumab; these will not be considered a separate line of therapy. Any chemotherapy regimen change due to toxicity in the absence of disease progression will be considered part of the same line of therapy.
• Has provided documented informed consent for the study.
• Has radiographic evidence of disease progression within 6 months (180 days) after the last dose of platinum-based chemotherapy for OC (i.e., platinum-resistant disease).
• Is a candidate for paclitaxel chemotherapy (and bevacizumab, if using).
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 assessed within 3 days before randomization.
• For a female participant, she is not pregnant or breastfeeding, and at least one of the following conditions applies: Is not a woman of childbearing potential (WOCBP) OR Is a WOCBP and uses a contraceptive method that is highly effective (with a failure rate of <1% per year).
• Has radiographically evaluable disease, either measurable or nonmeasurable per RECIST 1.1, as assessed by the local site investigator.
• Archival tumor tissue sample or newly obtained core or incisional/excisional biopsy of a tumor lesion not previously irradiated has been provided.
• Have adequate organ function

Criteri di esclusione: 

• Has nonepithelial cancers, borderline tumors, mucinous, seromucinous that is predominantly mucinous, malignant Brenner's tumor and undifferentiated carcinoma.
• Has primary platinum-refractory disease, defined as disease that has progressed per RECIST 1.1 while receiving first-line platinum-based therapy.
• Has prior disease progression on weekly paclitaxel alone.
• Has uncontrolled hypertension.
• Has current, clinically relevant bowel obstruction including related to underlying epithelial OC, abdominal fistula or gastrointestinal perforation, intra-abdominal abscess, or evidence of rectosigmoid involvement by pelvic exam.
• Has a history of thrombotic disorders, hemorrhage, hemoptysis, or active gastrointestinal bleeding within 6 months before randomization.
• Has received >2 prior lines of systemic therapy for OC.
• Has received prior systemic anticancer therapy including investigational agents within 4 weeks before randomization.
• Has received prior radiation therapy within 2 weeks of start of study intervention.
• Has not recovered adequately from surgery and/or any complications from the surgery.
• Has received colony-stimulating factors (e.g., granulocyte colony-stimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor,[GM-CSF] or recombinant erythropoietin) within 4 weeks before randomization.
• Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy.
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Has severe hypersensitivity (≥Grade 3) to pembrolizumab, paclitaxel, or bevacizumab (if using) and/or any of their excipients.
• Has an active autoimmune disease that has required systemic treatment in the past 2 years.
• Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
• Has an active infection requiring systemic therapy.
• Has a known history of human immunodeficiency virus (HIV) infection.
• Has a known history of Hepatitis B or known active Hepatitis C virus infection.
• Has a history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound the results of the study.
• Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.
• Participant, in the judgement of the investigator, is unlikely to comply with the study procedures, restrictions, and requirements of the study.
• Has had an allogenic tissue/solid organ transplant

Trattamento sperimentale: 

Pembro+Pacli+/-Beva

Trattamento di controllo: 

Placebo+Pacli+/-Beva

Centri partecipanti

Nord Italia

Informazioni Generali

Protocollo

Numero di iscrizione a registro: 2020-005027-37

Data di inserimento: 12.05.2022

Promotore

Merck Sharp & Dohme LLC

CRO

NA

Principal Investigator ITALIA

Istituto Europeo di Oncologia - IEO

Riferimento: Prof.ssa Nicoletta Colombo

Telefono: 0257489543

Email: nicoletta.colombo@ieo.it

Localita: Milano