platinum-sensitive recurrent low-grade serous ovarian cancer (including patients with primary peritoneal and / or fallopian tube adenocarcinoma) MedDRA version: 21.1 Level: PT Classification code 10066697 Term: Ovarian cancer recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: KEYTRUDA (pembrolizumab, MK3475)
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Pembrolizumab
CAS Number: 1374853-91-4
Concentration unit: mg/ml milligram(s)/millilitre
Co
Sponsors
NOGGO e.V.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Female, age at least 18 years. 2. Histologically diagnosed low-grade serous ovarian cancer, fallopian tube cancer, or primary peritoneal cancer. 3. 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 letrozole is allowed). Neoadjuvant chemotherapy in the first line therapy will be counted as one line of therapy. Patients may, but are not required to, have a previous cytoreductive surgery in the first as well as in the second line. 4. Patients must have platinum sensitive disease, e.g. progression or recurrence after platinum-containing therapy, occurring no sooner than 6 months after completion of the last dose of platinum chemotherapy. Definition Recurrence: Evidence of measurable or non-measurable tumor according to RECIST 1.1 criteria by imaging with or without increase of tumor marker CA-125 = 2x ULN OR histologically confirmed tumor recurrence by biopsy or surgery. 5. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. 6. Women of childbearing potential should not become pregnant while on the study therapy 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 study therapy. 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. 7. The participant provides written informed consent for the trial. 8. Have provided 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. Note: If submitting unstained cut slides, newly cut slides should be submitted to the testing laboratory within 14 days from the date slides are cut. 9. Have adequate organ and bone marrow function as defined in the following: Hematological: Absolute neutrophil count (ANC) =1500/µL, Platelets =100 000/µL, Hemoglobin =9.0 g/dL or =5.6 mmol/L; Renal: Creatinine =1.5 × ULN OR Measured or calculatedb creatinine clearance (GFR can also be used in place of creatinine or CrCl) =30 mL/min for participant with creatinine levels >1.5 × institutional ULN; Hepatic: Total bilirubin =1.5 ×ULN OR direct bilirubin =ULN for participants with total bilirubin levels >1.5 × ULN, AST (SGOT) and ALT (SGPT) =2.5 × ULN (=5 × ULN for participants with liver metastases); Coagulation: International normalized ratio (INR) OR prothrombin time (PT) Activated partial thromboplastin time (aPTT) =1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants. Blood samples must be collected within 10 days prior to the start of study treatment Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 23 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: 1. High-grade ovarian cancer. 2. Persistent =Grade 2 non-hematologic toxicity from prior cancer therapy 3. 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). 4. 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. 5. Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks. 6. 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. 7. Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed. 8.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. 9. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug. 10. 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, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded 11. Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment. 12. Has a bleeding tumor 13. Has hypersensitivity to any of the study drugs the patient will be treated with and/or to any of the excipients of the study drugs the patient will be treated with. 14. Has hypersensitivity to platin-containing compounds other than carboplatin. 15. Has active autoimmune disease that has required systemic treatment in the 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, etc.) is not considered a form of systemic treatment. 16. Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease. 17. Has an active infection requiring systemic therapy. 18. Has active infection with SARS-CoV-2 (antigen test). 19. Has a history of Human Immunodeficiency Virus (HIV) infection
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 12-month (48 weeks) progression free survival (PFS) rate ;Secondary Objective: ORR (objective response rate), OS (overall survival) and PFS rate after 6, 12, 18 and 24 months PFS and OS as time-to-event variables Response rate (Stable Disease, Partial Response or Complete Response) after 6, 12, 18 and 24 months Marker of proliferation Ki-67 Safety Endpoints – safety of combination therapy (chemotherapy and pembrolizumab) CTCAE 5.0 (National Cancer Institute: Common Terminology Criteria for Adverse Events) will be used as endpoint Time of subsequent medical intervention Time to first subsequent treatment (TFST) and response to first subsequent treatment Quality of live (Questionnaires EORTC-QLQ-C30, EORTC-QLQ-OV-28) until 6 months after progress ;Primary end point(s): The study is designed as a Phase II single-arm study to explore clinical activities in subjects with platinum sensitive low-grade ovarian cancer with 12-month Progression Free Survival (PFS) selected as the primary endpoint. The primary analysis of PFS will be based on the disease assessment by local imaging per irRECIST 1.1.;Timepoint(s) of evaluation of this end point: Progression Free Survival (PFS) will be evaluated 6, 12, 18 & 24 months after treatment start. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Collectively, the study will show anti-tumor response rate as well as durability of response, disease control, ORR rate and PFS rate at certain timepoints. This will provide a picture of overall antitumor activities of pembrolizumab in the selected low-grade ovarian cancer population: ORR (objective response rate), OS (overall survival) and PFS rate after 6, 12, 18 and 24 months PFS and OS as time-to-event variables Response rate (Stable Disease, Partial Response or Complete Response) after 6, 12, 18 and 24 months Marker of proliferation Ki-67 Safety Endpoints – safety of combination therapy (chemotherapy and pembrolizumab) CTCAE 5.0 (National Cancer Institute: Common Terminology Criteria for Adverse Events) will be used as endpoint Time of subsequent medical intervention Time to first subsequent treatment (TFST) and response to first subsequent treatment Quality of live (Questionnaires EORTC-QLQ-C30, EORTC-QLQ-OV-28) until 6 months after progress;Timepoint(s) of evaluation of this end point: every 6 months | — |
Countries
Germany
Contacts
Public ContactLeading Project Manager
NOGGO e.V.
Outcome results
None listed