The study is designed to assess the therapeutic efficacy and toxicity of the combination chemotherapy with pembrolizumab in recurrent, platinum resistant OC patients. The main objective is to test whether the therapeutic intervention benefits the patients evaluating the increase in overall survival with respect to chemotherapy alone.
This is a multicenter, randomized, open-label trial, designed to assess the therapeutic efficacy and toxicity of the combination chemotherapy with pembrolizumab in recurrent, platinum resistant OC patients. The main objective is to test whether the therapeutic intervention benefits the patients evaluating the increase in overall survival with respect to chemotherapy alone. Eligible patients will be randomized 1:1 to receive: ARM A: Pegylated Liposomal Doxorubicin 40 mg/mq iv q 28 Weekly Paclitaxel 80 mg/mq d 1,8,15 q 28 Gemcitabine 1000 mg/mq d 1,8 q 21 At physician' discretion or ARM B: Pegylated Liposomal Doxorubicin 40 mg/mq iv q 28 Weekly Paclitaxel 80 mg/mq d 1,8,15 q 28 Gemcitabine 1000 mg/mq d 1,8 q 21 plus Pembrolizumab 200 mg d1 q 21 iv infusion in 30 minutes In both arms patients will receive treatments until disease progression, unacceptable toxicity of patient's refusal. Patients will receive at least 6 to 8 cycles of chemotherapy at physician's discretion. In the experimental arm patients who stop chemotherapy for toxicity reasons and whose disease is at least in stabilization, may continue treatment with Pembrolizumab as single agent. Patients will be stratified according to the number of previous chemotherapy lines (1 vs \>1) and measurable/evaluable disease.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
138
Humanized antibody used in cancer immunotherapy.
Chemotherapy medication
Chemotherapy medication
National Cancer Institute
Milan, Italy
Overall survival (OS)
The combination of pembrolizumab and chemotherapy is expected to increase overall survival with respect to chemotherapy alone
Time frame: from randomization to the date of death, assessed up to 44 months
Progression free survival (PFS)
The combination of pembrolizumab and chemotherapy is expected to increase progression free survival with respect to chemotherapy alone
Time frame: from randomization to the date of radiological/clinical progression of disease or death, assessed up to 44 months
Response rate
The combination of pembrolizumab and chemotherapy is expected to increase response rate with respect to chemotherapy alone.
Time frame: 44 months
Adverse events
Incidence of adverse events, according to the National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 5.0
Time frame: 44 months
Exploratory Objective: relationship between PD-L1 expression and response to Pembrolizumab treatment.
PD-L1 expression in tumor tissue will be characterized by immunohistochemistry to explore the relationship between tumor PD-L1 expression and response to treatment with pembrolizumab.
Time frame: At screening phase: within 28 days before the start of treatment
Exploratory Objective: association between anti-tumor activity from genetic alterations that may indicate a specific genotype reflective of greater dependency on PD-1/PD-L1 checkpoint function or other immune checkpoint signaling pathways
DNA isolated from blood or tumor tissue will be analyzed in order to identify genetic alterations and to evaluate specific genetic alterations that may correlate with clinical response to Pembrolizumab.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Chemotherapy medication
Time frame: At screening phase (within 28 days before the start of treatment) and every 3 cycles (each cycle is 28 days), up to 44 months
Quality of life
To assess patient-reported outcome (PRO) of patients receiving chemotherapy plus pembrolizumab with respect to patients receiving chemotherapy alone utilizing the disease-related symptoms - physical subscale of the National Comprehensive Cancer Network-Functional Assessment of Cancer Therapy FACT-Ovarian Symptom Index 18 (FOSI-18) Changes. The time to an event in PRO (Patient Reported Outcome) of worsening of disease symptoms will be defined as the time from randomization to a 4-point reduction in the FACT-O questionnaire.
Time frame: 44 months
Quality of life
To assess patient-reported outcome (PRO) of patients receiving chemotherapy plus pembrolizumab with respect to patients receiving chemotherapy alone using Euro- Quality of Life 5D tool, indicating which statements best describe the patient health state regarding: mobility, self-care, usual activities, pain/discomfort, anxiety/depression
Time frame: 44 months