The purpose of this study is to determine if KM1 is well tolerated with anti-tumor activity in patients diagnosed with recurrent or refractory ovarian cancer, and explore the Recommend Phase 2 Dose (RP2D) of KM1 in the treatment of patients with recurrent or refractory ovarian cancer.
Oncolytic virus therapy is a kind of immunotherapy that can selectively infect and kill tumor cells without damaging normal cells. It has shown good therapeutic effects in the treatment of various types of tumors. KM1 is a genetically modified recombinant vaccinia virus, which has good therapeutic effect on many solid tumors, including ovarian cancer. This study includes Phase Ia and Phase Ib. In the Phase Ia study, subjects will receive three doses intraperitoneal infusion of KM1 followed by chemotherapy. In the Phase Ib study, subjects will receive six doses intraperitoneal infusion of KM1 preceding chemotherapy. Subjects will be followed in the study for 6 months after last dose of chemotherapy.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
Administer via intraperitoneal infusion for 3 or 6 doses Q3D.
Physician's Choice of carboplatin (preferred) or cisplatin,gemcitabine, taxane (paclitaxel, docetaxel or nab-paclitaxel) or pegylated liposomal doxorubicin,with or without bevacizumab. Administer beginning in Week 5 or Week 6.
Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology
Wuhan, Hubei, China
RECRUITINGDose-limiting toxicity (DLT)
Type and incidence of dose-limiting toxicity (DLT) by dose group
Time frame: From baseline during treatment to 21 days following last dose of KM1.
Adverse events (AEs) and serious adverse events (SAEs)
Type and incidence of adverse events (AEs) and serious adverse events (SAEs) by dose group
Time frame: From baseline during treatment to 21 days following last dose of KM1
Maximum tolerable dose (MTD)/ Recommended Phase II Dose (RP2D)
Time frame: From baseline during treatment to 21 days following last dose of KM1.
Virus particles
Level of virus particles tested by plaque assay in blood, body fluids (urine, feces and saliva), peritoneal fluid (if any), and tumor tissue (if any) at baseline and during treatment period.
Time frame: From baseline during treatment to 21 days following last dose of KM1.
Virus coding genes
Level of virus coding genes tested by PCR assay in blood, body fluids (urine, feces and saliva), peritoneal fluid (if any), and tumor tissue (if any) at baseline and during treatment period.
Time frame: From baseline during treatment to 21 days following last dose of KM1.
Anti-Drug Antibodies (ADA)
Titer of positive ADA against KM1 at baseline and during treatment period.
Time frame: From baseline during treatment to 21 days following last dose of KM1.
Progression Free Survival (PFS) by RECIST 1.1
Time from study treatment initiation to the first occurrence of disease progression or death (of any cause).
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Time frame: From date of randomization up to 6 months following last dose of chemotherapy.
Objective Response Rate (ORR) by RECIST 1.1
The ratio of the sum of Complete Response \& Partial Response divided by the number of participants from the start of treatment to confirmation of response.
Time frame: From date of randomization up to 6 months following last dose of chemotherapy.
Disease Control Rate (DCR) RECIST 1.1
The ratio of the sum of Complete Response \& Partial Response \& Stable Disease divided by the number of participants from the start of treatment to confirmation of response
Time frame: From date of randomization up to 6 months following last dose of chemotherapy.
CA-125 Response
Level of CA-125 (UI/ml) at baseline and after treatment measured by Enzyme Linked Immunosorbent Assay (ELISA).
Time frame: From date of randomization up to 6 months following last dose of chemotherapy.