Resumen

The purpose of this study is to assess the efficacy and safety of pembrolizumab (MK-3475) plus one of four platinum-based chemotherapy regimens compared to the efficacy and safety of placebo plus one of four platinum-based chemotherapy regimens in the treatment of adult women with persistent, recurrent, or metastatic cervical cancer. Possible chemotherapy regimens include: paclitaxel plus cisplatin with or without bevacizumab and paclitaxel plus carboplatin with or without bevacizumab. The primary study hypotheses are that the combination of pembrolizumab plus chemotherapy is superior to placebo plus chemotherapy with respect to: 1) Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST 1.1) as assessed by the Investigator, or, 2) Overall Survival (OS).

Elegibilidad

Edad mínima: 18 YearsSexo: FEMALE

Criterios de inclusión

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). Prior chemotherapy utilized as a radiosensitizing agent and completed at least 2 weeks prior to randomization with resolution of all treatment-related toxicities is allowed. AEs due to previous treatments should be resolved to ≤ Grade 1 or baseline. Participants with ≤ Grade 2 neuropathy or ≤ Grade 2 alopecia are eligible.
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 and 210 days after the last dose of chemotherapy/bevacizumab
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

Criterios de exclusión

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 major 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/bevacizumab
Has had an allogeneic tissue/solid organ transplant

Ubicaciones

Centro de Oncologia e Investigacion Buenos Aires COIBA ( Site 1006)

Berazategui, Buenos Aires, Argentina

Hospital Aleman ( Site 1005)

Buenos Aires, Argentina

Hospital de Oncologia Angel Roffo ( Site 1003)

Buenos Aires, Argentina

Instituto Medico Especializado Alexander Fleming ( Site 1009)

Buenos Aires, Argentina

Centro Oncologico Riojano Integral ( Site 1004)

La Rioja, Argentina

Centro Medico San Roque ( Site 1001)

San Miguel de Tucumán, Argentina

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 (KEYNOTE-826)

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Pembrolizumab

Paclitaxel

Cisplatin

Carboplatin

Bevacizumab

Placebo to pembrolizumab

Ubicaciones

Centro de Oncologia e Investigacion Buenos Aires COIBA ( Site 1006)

Hospital Aleman ( Site 1005)

Hospital de Oncologia Angel Roffo ( Site 1003)

Instituto Medico Especializado Alexander Fleming ( Site 1009)

Centro Oncologico Riojano Integral ( Site 1004)

Centro Medico San Roque ( Site 1001)

Patrocinadores