Phase 2 Study of JX-594 in Patients With Peritoneal Carcinomatosis of Ovarian Cancer Origin

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Ovarian Cancer
• Intervention / Treatment: Biological: JX-594

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

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada
      • Princess Margaret Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. 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.
2. Radiologically evaluable disease.
3. 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.
4. Expected survival ≥12 weeks
5. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
6. Women aged ≥18 years
7. 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
8. Signed informed consent form
9. No contraindications to undergo general anesthetic or laparoscopy.
10. 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:

1. 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
2. Therapeutic anticoagulant therapy
3. History of severe exfoliative skin condition (e.g., eczema or ectopic dermatitis requiring systemic therapy for more than 4 weeks)
4. Tumor(s) invading a major vascular structure (e.g., carotid artery)
5. Clinically significant and uncontrolled pericardial or pleural effusions
6. 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
7. Tumor burden >50% of abdominal cavity or malignant obstruction of small bowel or other condition that would preclude safe biopsy or laparoscopy
8. Brain metastasis: Viable central nervous system (CNS) malignancy associated with clinical symptoms (Note: enrollment allowed if completely resected or stable post radiotherapy >12 weeks).
9. Received anti-cancer therapy within 4 weeks prior to first treatment (6 weeks in case of mitomycin C or nitrosoureas)
10. Prior participation in other research protocol involving an investigational product within 4 weeks or 5 half-lives, whichever is longer, prior to first treatment
11. 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
12. 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)
13. 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)
14. Pregnant or nursing an infant
15. Pulse oximetry O2 saturation <90% at rest on room air
16. Experienced a severe systemic reaction or side-effect as a result of a previous smallpox vaccination.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: JX-594 IV Infusion; Patients with peritoneal carcinomatosis of ovarian origin that are not eligible for curative treatments will receive 5 weekly IV infusions of JX-594	Biological: JX-594; 5 weekly IV infusions of JX-594 followed by laparoscopy and biopsy on day 10 or 38.; Other Names: vaccinia virus

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Weekly
Response rate using modified immune criteria	Determine response rate using modified immune criteria in ovarian peritoneal carcinomatosis	6 weeks
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	Weekly
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.	Weekly
Immune response to JX-594	Determine the immune response to JX-594 by change in peripheral white blood cell counts over time	6 weeks
Response of tumour markers to JX-594	Determine serum tumor marker response rate	Weekly
Time to progressive disease	Determine time to progression of disease after JX-594 administration	6 weeks

Collaborators and Investigators

• Sponsor: Andrea McCart
• Collaborators: Ontario Institute for Cancer Research
• Investigators: Principal Investigator: Judith Andrea McCart, MD, Mount Sinai Hospital; Principal Investigator: Helen MacKay, MD, Princess Margaret Cancer Centre

Study record dates

Study Major Dates

• Study Start: January 1, 2014
• Primary Completion (ANTICIPATED): January 1, 2015
• Study Completion (ANTICIPATED): June 1, 2015

Study Registration Dates

• First Submitted: September 20, 2013
• First Submitted That Met QC Criteria: December 16, 2013
• First Posted (ESTIMATE): December 23, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): September 17, 2014
• Last Update Submitted That Met QC Criteria: September 15, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Keywords: Ovarian cancer; JX-594; Peritoneal; Oncolytic virus; Carcinomatosis; Vaccinia virus
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Peritoneal Diseases; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Digestive System Neoplasms; Endocrine Gland Neoplasms; Abdominal Neoplasms; Carcinoma; Ovarian Neoplasms; Peritoneal Neoplasms; Carcinoma, Ovarian Epithelial
• Other Study ID Numbers: OZM-044