This is a phase II, single arm, multi-centre study to assess the efficacy of pembrolizumab in combination with platinum-based chemotherapy (investigator's choice: carboplatin + gemcitabine or carboplatin + pegylated liposomal doxorubicin) administered concurrent to chemotherapy and in maintenance, in patients with low grade ovarian cancer (including patients with primary peritoneal and / or fallopian tube adenocarcinoma) having platinum-sensitive relapse (platinum-free interval \> 6 months).
In this study, we will evaluate efficacy and safety of pembrolizumab in combination with chemotherapy (physician's choice) in subjects with low-grade ovarian cancer. Patients will receive Pembrolizumab 200mg q3w until progression or unacceptable toxicity, for a maximum of 35 cycles PLUS one of the following standard chemotherapies for LGSOC (investigators' choice): Carboplatin AUC 4 + Gemcitabine 1000mg/m² (q3w for 3-6 cycles) or Carboplatin AUC 5 + pegylated liposomal Doxorubicin 30mg/m² (q4w for 3-6 cycles). As primary objective 12-month progression free survival (PFS) rate will be analysed. About 2 sites in Germany will participate in this study to recruit 33 patients in 24 months.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
33
Participants receive pembrolizumab 200 mg by intravenous (IV) infusion prior to chemotherapy on Day 1 of each 21-day cycle for up to 35 cycles
Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum
Berlin, Germany
Kliniken Essen Mitte
Essen, Germany
12-month (48 weeks) progression free survival (PFS) rate
The primary objective of this clinical trial is 12-month Progression Free Survival (PFS) rate after start of treatment. Tumor progression will be assessed with local imaging per irRECIST 1.1 and is defined according to RECIST criteria. Start of therapy will be counted when the patient receives the first dose of pembrolizumab.
Time frame: 12 month
Response rate (SD, PR or CR) after 6, 12, 18 and 24 months
Stable Disease, Partial Response or CR will be evaluated per irRECIST 1.1 after 6, 12,18 and 24 months
Time frame: 6, 12, 18 and 24 months
Ki-67
Marker of proliferation Ki-67 Obtain archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated for routine determination of PD-1, PD-L1 and Ki-67 status
Time frame: 24 month
Time of next medical intervention
Time of next medical intervention due to tumor progress
Time frame: 24 month
Quality of life until 6 months after progress
Patients are asked to answer the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30). Responses of questions 1-28 are based on a 4-point scale (1=not at all; 4=Very much), with a higher score indicating a high degree of symptomatology and must therefore be assessed negatively. Responses of questions 29 and 30 are based on a 7-point scale (1=Very poor; 7=Excellent), with a higher score indicating a better global health status.
Time frame: 6 month
TFST and response to first subsequent treatment
Time to first subsequent treatment and response to first subsequent treatment will be evaluated.
Time frame: 24 month
Safety Endpoints - safety of combination therapy (ctx and pembrolizumab) according to CTCAE 5.0 criteria will be used as endpoint
The safety objective is to characterize the safety and tolerability of pembrolizumab in combination with chemotherapy in subjects with advanced low grade ovarian cancer. The following safety parameters will be analyzed: adverse events and serious adverse events graded per NCI CTCAE, Version 4.0 criteria with time to onset/recovery, causality and outcome; changes in laboratory values, vital signs since baseline, treatment discontinuations and reason for discontinuation, death and cause of death etc. concomitant medications will be collected with time and reasons of use. These are routine safety parameters collected and analyzed in Phase II /III oncology trials. Furthermore, specific immune-related adverse events (irAEs) will be collected
Time frame: 24 month
PFS (time-to-event) and PFS rate after 6, 12, 18 and 24 months
Progression Free Survival (time to event) and PFS rate after 6, 12, 18 and 24 months after start of treatment. Tumor progression will be assessed with local imaging per irRECIST 1.1 and is defined according to RECIST criteria. Start of therapy will be counted when the patient receives the first dose of pembrolizumab
Time frame: 6, 12, 18 and 24 months
Quality of life 2 until 6 months after progress
Patients are asked to answer the EORTC QoL Questionnaire-Ovarian Cancer (QLQ-OV28). Responses are based on a 4-point scale (1=Not at all; 4=Very much), with a lower score indicating better symptoms.
Time frame: 6 month
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