Oncolytic Virotherapy Plus PD-1 Inhibitor for Patients With Refractory Malignant Ascites
Primary Purpose
Refractory Malignant Ascites
Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
H101
Tislelizumab
Sponsored by
About this trial
This is an interventional treatment trial for Refractory Malignant Ascites
Eligibility Criteria
Inclusion Criteria:
- Written informed consent obtained.
- Age ≥ 18 years at time of study entry.
- Pathologically diagnosed solid tumor malignancy.
- Malignant peritoneal ascites confirmed by peritoneal brush cytology.
- Failures from chemotherapy against malignant ascites.
- Cooperative Oncology Group-Status (ECOG Status) 0 or 1
Exclusion Criteria:
- Previous (<4 weeks) or concurrent treatment with systemic or intraperitoneal chemotherapy or biological agents such as monoclonal antibodies.
- History of cardiac disease, including clinically significant gastrointestinal bleeding within 4 weeks prior to start of study treatment
- Thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within the 6 months Prior to the first dose of study drug with the exception of thrombosis of a segmental portal vein.
- Prior treatment with oncolytic virotherapy.
- Radiotherapy administered less then 4 weeks prior to study treatment start.
- Major surgery within 4 weeks of starting the study treatment OR subjects who have not recovered from effects of major surgery.
- Patients with second primary cancer, except adequately treated basal skin cancer or carcinoma in-situ of the cervix.
- Immunocompromised patients, e.g. patients who are known to be serologically positive for human immunodeficiency virus (HIV).
- Participation in another clinical study with an investigational product during the last 30 days before inclusion or 7 half-lifes of previously used trial medication, whichever is longer.
- Any condition or comorbidity that, in the opinion of the investigator, would interfere with evaluation of study Treatment or interpretation of patient safety or study results, including but not limited to:
- history of interstitial lung disease
- Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) coinfection (i.e double infection)
- known acute or chronic pancreatitis
- active tuberculosis
- any other active infection (viral, fungal or bacterial) requiring systemic therapy
- history of allogeneic tissue/solid organ transplant
- diagnosis of immunodeficiency or patient is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of Tislelizumab treatment.
- Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Exceptions: Subjects with vitiligo, hypothyroidism, diabetes mellitus type I or resolved childhood asthma/atopy are an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with Hashimoto thyroiditis, hypothyroidism stable on hormone replacement or psoriasis not requiring treatment are not excluded from the study.
- Live vaccine within 30 days prior to the first dose of Tislelizumab treatment or during study treatment.
- History or clinical evidence of Central Nervous System (CNS) metastases Exceptions are: Subjects who have completed local therapy and who meet both of the following criteria: I. are asymptomatic and II. have no requirement for steroids 6 weeks prior to start of Tislelizumab treatment. Screening with CNS imaging (CT or MRI) is required only if clinically indicated or if the subject has a history of CNS
- Medication that is known to interfere with any of the agents applied in the trial.
- Any other efficacious cancer treatment except protocol specified treatment at study start.
- Patient has received any other investigational product within 28 days of study entry.
- Female subjects who are pregnant, breast-feeding or male/female patients of reproductive potential who are not employing an effective method of birth control (failure rate of less than 1% per year). [Acceptable methods of contraception are: implants, injectable contraceptives, combined oral contraceptives, intrauterine pessars (only hormonal devices), sexual abstinence or vasectomy of the partner]. Women of childbearing potential must have a negative pregnancy test (serum β-HCG) at screening.
Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent.
Sites / Locations
- Fudan University Shanghai Cancer CenterRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
H101 + Tislelizumab
Arm Description
(Dose escalation and cohort expansion) H101 administered by Intraperitoneal injection in combination with Tislelizumab administered intravenously (IV).
Outcomes
Primary Outcome Measures
Number of patient with dose-limiting toxicities (DLTs) as evaluated accordingly to CTCAE 5.0
The DLT assessment period is defined as: Day of Injection through 28 days post injection (Safety Follow Up). A DLT will be defined as any Grade 3 or higher adverse event, as assessed by the National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0.
Maximum tolerated dose (MTD) of intratumoral injection of H101 on at three dose levels in combination with anti-PD1 antibody.
A MTD is determined if any cohort experiences 2 subjects with DLT's.
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Secondary Outcome Measures
Ascites Objective Response Rate
The ascites objective response rate (ORR) was calculated as a summed ratio of patients with disappeared and decreased ascites to the total number of patients.
Objective Response Rate (ORR)
ORR according to RECIST 1.1
Duration of Response
Progression Free Survival
Overall survival
disease control rate
Change from baseline local immune effects after H101 intraperitoneal injections
Detection of increased local immune activation in malignant ascites will be assessed by single cell sequencing and/or Mass Cytometry (CyTOF).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05303844
Brief Title
Oncolytic Virotherapy Plus PD-1 Inhibitor for Patients With Refractory Malignant Ascites
Official Title
A Phase 1b Dose-escalation and Cohort-expansion Study of the Safety/Tolerability, and Efficacy of Oncolytic Virotherapy Plus PD-1 Inhibitor for Patients With Refractory Malignant Ascites (OPTIONS-02)
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 2, 2022 (Actual)
Primary Completion Date
March 20, 2025 (Anticipated)
Study Completion Date
March 20, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Fudan University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
The objective of this study is to evaluate the safety/tolerability efficacy of oncolytic virotherapy combined with Tislelizumab for patients with refractory malignant ascites.
Detailed Description
This study is to evaluate the safety, effectiveness of local immune activation, and efficiency in patients with refractory malignant ascites after Intraperitoneal injection of oncolytic Viruses H101 and Tislelizumab.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Refractory Malignant Ascites
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
25 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
H101 + Tislelizumab
Arm Type
Experimental
Arm Description
(Dose escalation and cohort expansion) H101 administered by Intraperitoneal injection in combination with Tislelizumab administered intravenously (IV).
Intervention Type
Drug
Intervention Name(s)
H101
Intervention Description
H101 intratumorally injection starts at day 0.
Intervention Type
Drug
Intervention Name(s)
Tislelizumab
Intervention Description
Tislelizumab will be initiated on day 1. Tislelizumab will be administered at 200 mg i.v. every 3 weeks until documented disease progression, development of unacceptable toxicity, participant request, or withdrawal of consent.
Primary Outcome Measure Information:
Title
Number of patient with dose-limiting toxicities (DLTs) as evaluated accordingly to CTCAE 5.0
Description
The DLT assessment period is defined as: Day of Injection through 28 days post injection (Safety Follow Up). A DLT will be defined as any Grade 3 or higher adverse event, as assessed by the National Cancer Institute Common Toxicity Criteria for Adverse Events (CTCAE) version 5.0.
Time Frame
28 days
Title
Maximum tolerated dose (MTD) of intratumoral injection of H101 on at three dose levels in combination with anti-PD1 antibody.
Description
A MTD is determined if any cohort experiences 2 subjects with DLT's.
Time Frame
28 days
Title
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Time Frame
max 24 months
Secondary Outcome Measure Information:
Title
Ascites Objective Response Rate
Description
The ascites objective response rate (ORR) was calculated as a summed ratio of patients with disappeared and decreased ascites to the total number of patients.
Time Frame
max 24 months
Title
Objective Response Rate (ORR)
Description
ORR according to RECIST 1.1
Time Frame
max 24 months
Title
Duration of Response
Time Frame
max 24 months
Title
Progression Free Survival
Time Frame
max 24 months
Title
Overall survival
Time Frame
max 42 months
Title
disease control rate
Time Frame
max 24 months
Title
Change from baseline local immune effects after H101 intraperitoneal injections
Description
Detection of increased local immune activation in malignant ascites will be assessed by single cell sequencing and/or Mass Cytometry (CyTOF).
Time Frame
max 24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Written informed consent obtained.
Age ≥ 18 years at time of study entry.
Pathologically diagnosed solid tumor malignancy.
Malignant peritoneal ascites confirmed by peritoneal brush cytology.
Failures from chemotherapy against malignant ascites.
Cooperative Oncology Group-Status (ECOG Status) 0 or 1
Exclusion Criteria:
Previous (<4 weeks) or concurrent treatment with systemic or intraperitoneal chemotherapy or biological agents such as monoclonal antibodies.
History of cardiac disease, including clinically significant gastrointestinal bleeding within 4 weeks prior to start of study treatment
Thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within the 6 months Prior to the first dose of study drug with the exception of thrombosis of a segmental portal vein.
Prior treatment with oncolytic virotherapy.
Radiotherapy administered less then 4 weeks prior to study treatment start.
Major surgery within 4 weeks of starting the study treatment OR subjects who have not recovered from effects of major surgery.
Patients with second primary cancer, except adequately treated basal skin cancer or carcinoma in-situ of the cervix.
Immunocompromised patients, e.g. patients who are known to be serologically positive for human immunodeficiency virus (HIV).
Participation in another clinical study with an investigational product during the last 30 days before inclusion or 7 half-lifes of previously used trial medication, whichever is longer.
Any condition or comorbidity that, in the opinion of the investigator, would interfere with evaluation of study Treatment or interpretation of patient safety or study results, including but not limited to:
history of interstitial lung disease
Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) coinfection (i.e double infection)
known acute or chronic pancreatitis
active tuberculosis
any other active infection (viral, fungal or bacterial) requiring systemic therapy
history of allogeneic tissue/solid organ transplant
diagnosis of immunodeficiency or patient is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of Tislelizumab treatment.
Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents. Exceptions: Subjects with vitiligo, hypothyroidism, diabetes mellitus type I or resolved childhood asthma/atopy are an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Subjects with Hashimoto thyroiditis, hypothyroidism stable on hormone replacement or psoriasis not requiring treatment are not excluded from the study.
Live vaccine within 30 days prior to the first dose of Tislelizumab treatment or during study treatment.
History or clinical evidence of Central Nervous System (CNS) metastases Exceptions are: Subjects who have completed local therapy and who meet both of the following criteria: I. are asymptomatic and II. have no requirement for steroids 6 weeks prior to start of Tislelizumab treatment. Screening with CNS imaging (CT or MRI) is required only if clinically indicated or if the subject has a history of CNS
Medication that is known to interfere with any of the agents applied in the trial.
Any other efficacious cancer treatment except protocol specified treatment at study start.
Patient has received any other investigational product within 28 days of study entry.
Female subjects who are pregnant, breast-feeding or male/female patients of reproductive potential who are not employing an effective method of birth control (failure rate of less than 1% per year). [Acceptable methods of contraception are: implants, injectable contraceptives, combined oral contraceptives, intrauterine pessars (only hormonal devices), sexual abstinence or vasectomy of the partner]. Women of childbearing potential must have a negative pregnancy test (serum β-HCG) at screening.
Patient with any significant history of non-compliance to medical regimens or with inability to grant reliable informed consent.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Peng Wang, MD
Phone
86-21-64175590
Email
peng_wang@fudan.edu.cn
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peng Wang, MD
Organizational Affiliation
Fudan University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Fudan University Shanghai Cancer Center
City
Shanghai
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Peng Wang, MD
Phone
86-21-64175590
Email
wangp413@163.com
12. IPD Sharing Statement
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Oncolytic Virotherapy Plus PD-1 Inhibitor for Patients With Refractory Malignant Ascites
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