Trial Title:
Safety and Efficacy of KM1 in Subjects With Recurrent or Refractory Ovarian Cancer
NCT ID:
NCT05684731
Condition:
Ovarian Cancer
Conditions: Official terms:
Ovarian Neoplasms
Carcinoma, Ovarian Epithelial
Conditions: Keywords:
KM1
oncolytic virus
immunotherapy
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Intervention model description:
The study is a multicenter, open label, non-controlled, exploratory study. The "3+3" dose
escalation design will be implemented to evaluate the safety and tolerability of KM1 in
the treatment of subjects with recurrent or refractory ovarian cancer.
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
KM1
Description:
Administer via intraperitoneal infusion for 3 or 6 doses Q3D.
Arm group label:
Experimental: KM1 + Chemotherapy
Intervention type:
Drug
Intervention name:
Chemotherapy
Description:
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.
Arm group label:
Experimental: KM1 + Chemotherapy
Summary:
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.
Detailed description:
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Histologically or cytopathology confirmed epithelial ovarian cancer, fallopian tube
cancer or primary peritoneal cancer, except mucinous cancer.
- Relapsed/refractory subjects who failed to receive systemic treatment (at least one
standard platinum containing regimen); Note: If the disease relapses, there should
be evidence showing imaging or clinical progress (such as cytological report of new
ascites or pleural effusion). Only the increase of CA125 cannot be used as the
standard of disease recurrence.
- Performance status ECOG of 0 or 1.
- Life expectancy of at least 3 months.
- Toxicities of prior therapies have not been resolved to Grade 1 or baseline (except
for alopecia, pigmentation or other toxicity considered as no safety risk to the
subject in the study).
- At least 1 measurable target lesion by RECIST 1.1.
- Adequate renal, hepatic, bone marrow function, adequate coagulation tests, adequate
immune function by lymphocyte count.
- Pregnancy test results within 14 days before the treatment were negative. Subjects
of childbearing age must agree to use at least one medically approved contraceptive
measure (such as surgical sterilization, oral contraceptives, intrauterine devices,
sexual desire control, etc.) during the study treatment and at least 6 months after
the last trial drug treatment;
- Subjects voluntarily participated in the study, signed the informed consent form,
had good compliance and cooperated with the follow-up.
Exclusion Criteria:
- • Central nervous system (CNS) metastasis or cancerous meningitis (Note: Subjects
with treated CNS metastases may participate in this trial if the subject is
neurologically stable ≥3 months).
- Prior malignancy of other histology active within previous 3 years except for
locally curable cancers apparently cured such as basal/squamous cell skin
cancer, superficial bladder cancer, carcinoma in situ of cervix or breast.
- Received any of the following treatments within a specific time frame prior to
enrollment:
1. Have received surgery of Grade II or above within 4 weeks (Whether or not
related to tumor), except minimally invasive surgery under
gastrointestinal endoscopy;
2. Have received radiotherapy within 2 weeks (the investigator can judge the
appropriate time of enrollment according to the patient's toxicity
recovery after radiotherapy);
3. Within 4 weeks or participating in other therapeutic/interventional
clinical studies;
4. Have received local anti-tumor treatment within 4 weeks;
- Allergic to the test drug or its active ingredients and excipients.
- Has had severe allergic reaction after receiving smallpox vaccine in the past.
- Has a history of severe skin diseases requiring systemic treatment within 2
years, such as eczema, atopic dermatitis, burns, seborrheic dermatitis,
psoriasis, severe acne, etc.
- Has had an allogenic tissue/solid organ transplant.
- Active infection or fever of unknown cause (>38.5 ℃).
- Active pulmonary tuberculosis (TB) who are receiving anti tuberculosis
treatment or who have received anti tuberculosis treatment within 1 year before
screening;
- Positive anti-HIV (+) or anti-HCV (+) or syphilis specific antibody (TPHA) or
active hepatitis B.
- Has a history of serious cardiovascular or cerebrovascular diseases, including
but not limited to:
1. New York Heart Association (NYHA) congestive heart failure of grade III or
above;
2. Serious arrhythmia requiring drug treatment;
3. Acute myocardial infarction, severe or unstable angina, coronary or
peripheral artery bypass grafting, and stenting occurred within 6 months;
4. Left ventricular ejection fraction (EF)<60%;
5. QTcF interval ≥ 460 ms, or there are risk factors of torsade de pointes
ventricular tachycardia, such as hypokalemia, family history of long QT
syndrome or family history of arrhythmia (such as preexcitation syndrome);
6. Presence of uncontrolled hypertension (systolic blood pressure >160 mmHg
or diastolic BP>100 mmHg).
- Active autoimmune diseases such as inflammatory bowel disease, idiopathic
thrombocytopenic purpura, lupus erythematosus, autohemolytic anemia,
scleroderma, severe psoriasis, rheumatoid arthritis), but the following
conditions are allowed to enter the screening: type I diabetes, hypothyroidism
that can be controlled only through alternative treatment, skin diseases that
do not need systemic treatment (such as vitiligo, psoriasis or alopecia).
- Symptomatic malignant ascites or pleural effusions defined as rapidly
progressive ascites with abdominal distension and gastrointestinal dysfunction,
pleural effusions with respiratory difficulties requiring frequent paracentesis
> once every 14 days.
- Contraindications for intraperitoneal (IP) catheter placement: Bowel
obstruction with distended abdomen, rigid abdomen with bulky anterior wall
carcinomatosis, abdominal wall hernia mesh that precludes laparoscopic entry to
abdomen.
- Active gastrointestinal bleeding.
- Accompanied by unstable mental illness, alcohol abuse, drug abuse or drug
abuse.
- Other conditions that investigator considers unsuitable for this study.
Gender:
Female
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology
Address:
City:
Wuhan
Zip:
430030
Country:
China
Status:
Recruiting
Contact:
Last name:
Qinglei Gao, PhD, MD
Phone:
+86-13871127473
Email:
qingleigao@hotmail.com
Investigator:
Last name:
Qinglei Gao, PhD, MD
Email:
Principal Investigator
Start date:
February 1, 2023
Completion date:
June 1, 2026
Lead sponsor:
Agency:
Tongji Hospital
Agency class:
Other
Collaborator:
Agency:
Qilu Hospital of Shandong University
Agency class:
Other
Collaborator:
Agency:
People's Hospital of Quzhou
Agency class:
Other
Collaborator:
Agency:
Shenzhen Hua Yao Kang Ming Biopharmaceutical Co., Ltd.
Agency class:
Other
Source:
Tongji Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05684731
