Phase II Investigational Study of Pembrolizumab Combination With Chemotherapy in Platinum-sensitive Recurrent Low-grade Serous Ovarian Cancer
Overview
- Phase
- Phase 2
- Intervention
- Pembrolizumab
- Conditions
- Ovarian Cancer
- Sponsor
- North Eastern German Society of Gynaecological Oncology
- Enrollment
- 33
- Locations
- 2
- Primary Endpoint
- 12-month (48 weeks) progression free survival (PFS) rate
- Status
- Active, Not Recruiting
- Last Updated
- 11 months ago
Overview
Brief Summary
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).
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Female, age at least 18 years.
- •Histologically diagnosed low-grade serous ovarian cancer, fallopian tube cancer, or primary peritoneal cancer.
- •Patients must have completed at least 1 previous course of platinum-containing therapy (e.g., combination with carboplatin or cisplatin. Maintenance therapy with bevacizumab and/or endocrine agents is allowed).
- •Progression or recurrence after platinum-containing therapy, occurring no sooner than 6 months after completion of the last dose of platinum chemotherapy (platinum sensitive disease).
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or
- •Women of childbearing potential should not become pregnant while on the Product and should not be pregnant at the beginning of treatment. A pregnancy test should be performed on all women of childbearing potential prior to receiving the Product. Women of childbearing potential must agree to follow contraceptive guidance during the treatment period and for 6 months after receiving the last dose of the study therapy.
- •The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
- •Availability of archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue.
Exclusion Criteria
- •High-grade ovarian cancer.
- •Persistent ≥Grade 2 hematologic toxicity from prior cancer therapy Note: Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible.
- •Note: If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
- •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., CTLA-4, OX 40, CD137).
- •Is eligible for carboplatin-based doublet therapy in combination with bevacizumab in the relapse situation, since no treatment with bevacizumab has been administered in the first line therapy.
- •Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks.
- •Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease.
- •Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.
- •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 the first dose of study treatment.
- •Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
Arms & Interventions
Pembrolizumab + Chemotherapie
pembrolizumab in combination with platinum-based chemotherapy (investigator's choice: carboplatin + gemcitabine or carboplatin + pegylated liposomal doxorubicin)
Intervention: Pembrolizumab
Outcomes
Primary Outcomes
12-month (48 weeks) progression free survival (PFS) rate
Time Frame: 12 month
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.
Secondary Outcomes
- Time of next medical intervention(24 month)
- Response rate (SD, PR or CR) after 6, 12, 18 and 24 months(6, 12, 18 and 24 months)
- Safety Endpoints - safety of combination therapy (ctx and pembrolizumab) according to CTCAE 5.0 criteria will be used as endpoint(24 month)
- Ki-67(24 month)
- Quality of life until 6 months after progress(6 month)
- TFST and response to first subsequent treatment(24 month)
- PFS (time-to-event) and PFS rate after 6, 12, 18 and 24 months(6, 12, 18 and 24 months)
- Quality of life 2 until 6 months after progress(6 month)