Phase 2 Study of JX-594 in Patients With Peritoneal Carcinomatosis of Ovarian Cancer Origin
Primary Purpose
Ovarian Cancer
Status
Withdrawn
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
JX-594
Sponsored by
About this trial
This is an interventional treatment trial for Ovarian Cancer focused on measuring JX-594, Ovarian cancer, Peritoneal, Carcinomatosis, Vaccinia virus, Oncolytic virus
Eligibility Criteria
Inclusion Criteria:
- Histologically confirmed ovarian carcinomatosis with; no curative treatment options available, or the patient has refused or cannot tolerate the standard therapy. Patients must have had prior primary platinum based chemotherapy.
- Radiologically evaluable disease.
- At least 2 tumor masses amenable to biopsy (excisional or core) or laparoscopy. Tumor masses selected cannot be followed by Response Evaluation Criteria in Solid Tumors 1.1.
- Expected survival ≥12 weeks
- Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- Women aged ≥18 years
- Sexually active patients must be able and willing to abstain for a minimum of 15 days after treatment with JX-594 and subsequently use barrier method for at least 6 weeks after the last JX-594 treatment
- Signed informed consent form
- No contraindications to undergo general anesthetic or laparoscopy.
- Laboratory requirements:
Hematology
- Absolute neutrophil count (ANC) ≥1.0 x 109/L
- Lymphocytes ≥0.5 x109/L
- Hemoglobin ≥90 g/L (correction with transfusion or erythropoietin based therapy allowed)
- Platelet count ≥75 x 109/L
Biochemistry
- Total bilirubin ≤1.5 x upper limit of normal (ULN)
- Alkaline Phosphatase (ALP), Aspartate transaminase (AST), alanine aminotransferase (ALT) ≤3 x ULN (if patient exhibits liver metastasis, up to 5 x ULN acceptable)
- Serum creatinine ≤1.5 x ULN or creatinine clearance is ≥1.0 mL/s according to Cockroft-Gault formula
- International normalized ratio (INR) ≤1.5 Serum chemistries within normal limits (WNL) or Grade 1 (with exception of sodium, potassium, glucose, calcium, phosphate,magnesium, chloride upon Investigator discretion)
Exclusion Criteria:
- Significant immunodeficiency due to underlying illness (e.g., known HIV/AIDS) and/or medication (e.g., systemic corticosteroids taken for more than 4 weeks within the preceding 3 months). Intermittent doses of corticosteroids as an antiemetic for chemotherapy are acceptable. Patients have to be off continuous steroids for at least 4 weeks
- Therapeutic anticoagulant therapy
- History of severe exfoliative skin condition (e.g., eczema or ectopic dermatitis requiring systemic therapy for more than 4 weeks)
- Tumor(s) invading a major vascular structure (e.g., carotid artery)
- Clinically significant and uncontrolled pericardial or pleural effusions
- Severe or unstable cardiac disease, including significant coronary artery disease (e.g., requiring angioplasty or stenting) within the preceding 12 months, unless well-controlled and on stable medical therapy for at least 3 months
- Tumor burden >50% of abdominal cavity or malignant obstruction of small bowel or other condition that would preclude safe biopsy or laparoscopy
- Brain metastasis: Viable central nervous system (CNS) malignancy associated with clinical symptoms (Note: enrollment allowed if completely resected or stable post radiotherapy >12 weeks).
- Received anti-cancer therapy within 4 weeks prior to first treatment (6 weeks in case of mitomycin C or nitrosoureas)
- Prior participation in other research protocol involving an investigational product within 4 weeks or 5 half-lives, whichever is longer, prior to first treatment
- Medical condition, laboratory abnormality or active infection that in the judgment of the Principal Investigator may increase the risk associated with study participation or may prevent laparoscopy or may interfere with interpretation of study results and/or otherwise make the patient inappropriate for study entry
- Use of interferon/pegylated interferon (PEG-IFN) or ribavirin that cannot be discontinued within 14 days prior to any JX-594 dose. (Note: please consult Ozmosis Research Inc. if patient is taking any other anti-viral medications to determine eligibility)
- Unable to receive IV contrast for CT scanning due to documented history of iodinated contrast allergy unless controlled by medical intervention (e.g., premedication with steroids, diphenhydramine, or other anti-allergic medications)
- Pregnant or nursing an infant
- Pulse oximetry O2 saturation <90% at rest on room air
- Experienced a severe systemic reaction or side-effect as a result of a previous smallpox vaccination.
Sites / Locations
- Princess Margaret Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
JX-594 IV Infusion
Arm Description
Patients with peritoneal carcinomatosis of ovarian origin that are not eligible for curative treatments will receive 5 weekly IV infusions of JX-594
Outcomes
Primary Outcome Measures
Radiographic response of ovarian peritoneal carcinomatosis to JX-594 treatment
Determine radiographic response rate (response evaluation criteria in solid tumors [modified Response Evaluation Criteria in Solid Tumors 1.1])to JX-595
Secondary Outcome Measures
Assessment of Adverse Events related to JX-594 administered by repetitive IV infusion
Collection of incidence(s) of treatment-emergent adverse events will be tabulated and stratified by severity and relationship to JX-594 administration
Response rate using modified immune criteria
Determine response rate using modified immune criteria in ovarian peritoneal carcinomatosis
Delivery of JX-594 in solid tumours
Determine the delivery of JX-594 to solid tumors after repetitive IV infusion in patients with peritoneal carcinomatosis
JX-594 Secondary Replication in blood over time
Determine the pharmacokinetics of JX-594 by examining secondary replication of viral genomes in blood over time.
Immune response to JX-594
Determine the immune response to JX-594 by change in peripheral white blood cell counts over time
Response of tumour markers to JX-594
Determine serum tumor marker response rate
Time to progressive disease
Determine time to progression of disease after JX-594 administration
Full Information
NCT ID
NCT02017678
First Posted
September 20, 2013
Last Updated
September 15, 2014
Sponsor
Andrea McCart
Collaborators
Ontario Institute for Cancer Research
1. Study Identification
Unique Protocol Identification Number
NCT02017678
Brief Title
Phase 2 Study of JX-594 in Patients With Peritoneal Carcinomatosis of Ovarian Cancer Origin
Official Title
A Single-arm, Open-label, Phase 2 Study of JX-594 (Thymidine Kinase-Deactivated Vaccinia Virus Plus GM-CSF) Administered by 5 Weekly Intravenous (IV) Infusions in Patients With Peritoneal Carcinomatosis of Ovarian Cancer Origin
Study Type
Interventional
2. Study Status
Record Verification Date
September 2014
Overall Recruitment Status
Withdrawn
Study Start Date
January 2014 (undefined)
Primary Completion Date
January 2015 (Anticipated)
Study Completion Date
June 2015 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Andrea McCart
Collaborators
Ontario Institute for Cancer Research
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a single-arm open-label Phase 2 study in patients with peritoneal carcinomatosis of ovarian origin that are not eligible for curative treatments. Patients will receive 5 weekly IV infusions of JX-594 until radiographically determined progressive disease. Patients will be allotted in a 1:1 ratio to undergo a laparoscopy and tumor biopsy 10 days after dose 1 or 10 days after Dose 5. Patients will be monitored on study until evidence of progression or death or for 12 months post treatment.
Detailed Description
This is a single-arm open-label Phase 2 study in patients with peritoneal carcinomatosis of ovarian origin that are not eligible for curative treatments. Patients will receive 5 weekly IV infusions of JX-594 and will continue to receive IV infusion of JX-594 every 3 weeks until radiographically determined progressive disease. Using a 2 stage trial design, if 2 or more of the first 15 patients show a clinical response as defined by Response Evaluation Criteria in Solid Tumors 1.10 criteria (or if 3 of the 15 have stable disease as defined by Modified Response Evaluation Criteria in Solid Tumors 1.1 or clinically), the arm will be expanded to a total of 25 patients (Stage 2).
In Stage 1, patients will be allotted in a 1:1 ratio to undergo a laparoscopy and tumor biopsy 10 days after dose 1 or 10 days after Dose 5. A decision as to whether laparoscopy will be performed in Stage 2 will be reached at the conclusion of Stage 1.
Patients will be monitored on study until evidence of progression or death or for 12 months post treatment
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ovarian Cancer
Keywords
JX-594, Ovarian cancer, Peritoneal, Carcinomatosis, Vaccinia virus, Oncolytic virus
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
JX-594 IV Infusion
Arm Type
Experimental
Arm Description
Patients with peritoneal carcinomatosis of ovarian origin that are not eligible for curative treatments will receive 5 weekly IV infusions of JX-594
Intervention Type
Biological
Intervention Name(s)
JX-594
Other Intervention Name(s)
vaccinia virus
Intervention Description
5 weekly IV infusions of JX-594 followed by laparoscopy and biopsy on day 10 or 38.
Primary Outcome Measure Information:
Title
Radiographic response of ovarian peritoneal carcinomatosis to JX-594 treatment
Description
Determine radiographic response rate (response evaluation criteria in solid tumors [modified Response Evaluation Criteria in Solid Tumors 1.1])to JX-595
Time Frame
6 weeks
Secondary Outcome Measure Information:
Title
Assessment of Adverse Events related to JX-594 administered by repetitive IV infusion
Description
Collection of incidence(s) of treatment-emergent adverse events will be tabulated and stratified by severity and relationship to JX-594 administration
Time Frame
Weekly
Title
Response rate using modified immune criteria
Description
Determine response rate using modified immune criteria in ovarian peritoneal carcinomatosis
Time Frame
6 weeks
Title
Delivery of JX-594 in solid tumours
Description
Determine the delivery of JX-594 to solid tumors after repetitive IV infusion in patients with peritoneal carcinomatosis
Time Frame
Weekly
Title
JX-594 Secondary Replication in blood over time
Description
Determine the pharmacokinetics of JX-594 by examining secondary replication of viral genomes in blood over time.
Time Frame
Weekly
Title
Immune response to JX-594
Description
Determine the immune response to JX-594 by change in peripheral white blood cell counts over time
Time Frame
6 weeks
Title
Response of tumour markers to JX-594
Description
Determine serum tumor marker response rate
Time Frame
Weekly
Title
Time to progressive disease
Description
Determine time to progression of disease after JX-594 administration
Time Frame
6 weeks
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically confirmed ovarian carcinomatosis with; no curative treatment options available, or the patient has refused or cannot tolerate the standard therapy. Patients must have had prior primary platinum based chemotherapy.
Radiologically evaluable disease.
At least 2 tumor masses amenable to biopsy (excisional or core) or laparoscopy. Tumor masses selected cannot be followed by Response Evaluation Criteria in Solid Tumors 1.1.
Expected survival ≥12 weeks
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
Women aged ≥18 years
Sexually active patients must be able and willing to abstain for a minimum of 15 days after treatment with JX-594 and subsequently use barrier method for at least 6 weeks after the last JX-594 treatment
Signed informed consent form
No contraindications to undergo general anesthetic or laparoscopy.
Laboratory requirements:
Hematology
Absolute neutrophil count (ANC) ≥1.0 x 109/L
Lymphocytes ≥0.5 x109/L
Hemoglobin ≥90 g/L (correction with transfusion or erythropoietin based therapy allowed)
Platelet count ≥75 x 109/L
Biochemistry
Total bilirubin ≤1.5 x upper limit of normal (ULN)
Alkaline Phosphatase (ALP), Aspartate transaminase (AST), alanine aminotransferase (ALT) ≤3 x ULN (if patient exhibits liver metastasis, up to 5 x ULN acceptable)
Serum creatinine ≤1.5 x ULN or creatinine clearance is ≥1.0 mL/s according to Cockroft-Gault formula
International normalized ratio (INR) ≤1.5 Serum chemistries within normal limits (WNL) or Grade 1 (with exception of sodium, potassium, glucose, calcium, phosphate,magnesium, chloride upon Investigator discretion)
Exclusion Criteria:
Significant immunodeficiency due to underlying illness (e.g., known HIV/AIDS) and/or medication (e.g., systemic corticosteroids taken for more than 4 weeks within the preceding 3 months). Intermittent doses of corticosteroids as an antiemetic for chemotherapy are acceptable. Patients have to be off continuous steroids for at least 4 weeks
Therapeutic anticoagulant therapy
History of severe exfoliative skin condition (e.g., eczema or ectopic dermatitis requiring systemic therapy for more than 4 weeks)
Tumor(s) invading a major vascular structure (e.g., carotid artery)
Clinically significant and uncontrolled pericardial or pleural effusions
Severe or unstable cardiac disease, including significant coronary artery disease (e.g., requiring angioplasty or stenting) within the preceding 12 months, unless well-controlled and on stable medical therapy for at least 3 months
Tumor burden >50% of abdominal cavity or malignant obstruction of small bowel or other condition that would preclude safe biopsy or laparoscopy
Brain metastasis: Viable central nervous system (CNS) malignancy associated with clinical symptoms (Note: enrollment allowed if completely resected or stable post radiotherapy >12 weeks).
Received anti-cancer therapy within 4 weeks prior to first treatment (6 weeks in case of mitomycin C or nitrosoureas)
Prior participation in other research protocol involving an investigational product within 4 weeks or 5 half-lives, whichever is longer, prior to first treatment
Medical condition, laboratory abnormality or active infection that in the judgment of the Principal Investigator may increase the risk associated with study participation or may prevent laparoscopy or may interfere with interpretation of study results and/or otherwise make the patient inappropriate for study entry
Use of interferon/pegylated interferon (PEG-IFN) or ribavirin that cannot be discontinued within 14 days prior to any JX-594 dose. (Note: please consult Ozmosis Research Inc. if patient is taking any other anti-viral medications to determine eligibility)
Unable to receive IV contrast for CT scanning due to documented history of iodinated contrast allergy unless controlled by medical intervention (e.g., premedication with steroids, diphenhydramine, or other anti-allergic medications)
Pregnant or nursing an infant
Pulse oximetry O2 saturation <90% at rest on room air
Experienced a severe systemic reaction or side-effect as a result of a previous smallpox vaccination.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Judith Andrea McCart, MD
Organizational Affiliation
MOUNT SINAI HOSPITAL
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Helen MacKay, MD
Organizational Affiliation
Princess Margaret Cancer Centre
Official's Role
Principal Investigator
Facility Information:
Facility Name
Princess Margaret Cancer Center
City
Toronto
State/Province
Ontario
Country
Canada
12. IPD Sharing Statement
Learn more about this trial
Phase 2 Study of JX-594 in Patients With Peritoneal Carcinomatosis of Ovarian Cancer Origin
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