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A Phase 3 Randomized, Double-Blind, Placebo-Controlled Trial of Pembrolizumab (MK-3475) Plus Chemotherapy Versus Chemotherapy Plus Placebo for the First-Line Treatment of Persistent, Recurrent, or Metastatic Cervical Cancer - MK-3475-826 (KEYNOTE-826)

Studio Clinico

Patologia: Tumori dell’utero

Osservazionale-Sperimentale: Sperimentale

Monocentrico-Multicentrico: Multicentrico

Randomizzato: 

Fase di studio: III

Richiesta mandatoria di tessuto: 

Linee di trattamento: Prima linea

Criteri di inclusione: 

- Has persistent, recurrent, or metastatic squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix which has not been treated with systemic chemotherapy and is not amenable to curative treatment (such as with surgery and/or radiation)
- Not pregnant or breastfeeding, and at least one of the following conditions applies: a.) Not a woman of childbearing potential (WOCBP), b.) A WOCBP must agree to use effective contraception during the treatment period and for at least 120 days after the last dose of pembrolizumab/placebo or 210 days after the last dose of chemotherapy
- Has measurable disease per RECIST 1.1 as assessed by the local site investigator/radiology
- Has provided archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated for prospective determination of Programmed Cell Death-Ligand 1 (PD-L1) status prior to randomization
- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 within 14 days prior to randomization
- Has adequate organ function

Criteri di esclusione: 

- A WOCBP who has a positive urine pregnancy test within 72 hours prior to randomization
- Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with known brain metastases may participate provided that the brain metastases have been previously treated (except with chemotherapy) and are radiographically stable.
- Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, transitional cell carcinoma of urothelial cancer, or carcinoma in situ (e.g. breast cancer) that have undergone potentially curative therapy are not excluded.
- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in doses exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to randomization
- Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed
- Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
- 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 known history of active tuberculosis (TB; Bacillus tuberculosis)
- Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], OX 40, CD137)
- Has received prior systemic chemotherapy for treatment of cervical cancer.
- Has not recovered adequately from toxicity and/or complications from surgery prior to randomization
- Has received prior radiotherapy within 2 weeks prior to randomization. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.
- Has received a live vaccine within 30 days prior to randomization
- Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
- Has a contraindication or hypersensitivity to any component of cisplatin, carboplatin, paclitaxel, or bevacizumab
- Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to randomization
- Is pregnant or breastfeeding or expecting to conceive within the projected duration of the study, starting with the screening visit through 120 days following last dose of pembrolizumab/placebo and 210 days following last dose of chemotherapy
- Has had an allogeneic tissue/solid organ transplant

Schema di trattamento: 

Experimental: On Day 1 of each 21-day cycle, participants receive an intravenous (IV) infusion of pembrolizumab 200 mg PLUS Investigator choice of chemotherapy (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg OR paclitaxel 175 mg/m^2 PLUS carboplatin Area Under the Curve (AUC) 5, WITH or WITHOUT bevacizumab 15 mg/kg). All treatments are administered until disease progression or toxicity, for up to 35 cycles (up to approximately 2 years).

Placebo comparator: On Day 1 of each 21-day cycle, participants receive an IV infusion of placebo (Normal Saline or Dextrose solution) PLUS Investigator choice of chemotherapy (paclitaxel 175 mg/m^2 PLUS cisplatin 50 mg/m^2 WITH or WITHOUT bevacizumab 15 mg/kg OR paclitaxel 175 mg/m^2 PLUS carboplatin AUC 5, WITH or WITHOUT bevacizumab 15 mg/kg). All treatments are administered until disease progression or toxicity, for up to 35 cycles (up to approximately 2 years).

Trattamento sperimentale: 

Pembrolizumab+Chemotherapy

Trattamento di controllo: 

Placebo+Chemotherapy

Obiettivi primari dello studio: 

- Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by Blinded Independent Central Review (BICR) [ Time Frame: Up to approximately 2 years ]
    PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥ 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more new lesions was also considered PD. The PFS per RECIST 1.1 as assessed by BICR will be presented.

- Overall Survival (OS) [ Time Frame: Up to approximately 2 years ]
    OS is defined as the time from randomization to death due to any cause. The OS will be presented.

Centri partecipanti

Centro Italia

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

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

 

Sud Italia e isole

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: 2018-001440-53

Data di inserimento: 12.02.2019

Promotore

Merck Sharp & Dohme Corp.

CRO

/

Principal Investigator ITALIA

Fondazione Policlinico Universitario A. Gemelli, Roma

Riferimento: Prof. Giovanni Scambia

Telefono: 0630156134

Email: giovanni.scambia@unicatt.it

Localita: Roma

 

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