A Study of GL-ONC1, an Oncolytic Vaccinia Virus, in Patients With Advanced Peritoneal Carcinomatosis

March 9, 2015 updated by: Genelux GmbH

Phase I/II Study of Intraperitoneal Administration of GL-ONC1, a Genetically Modified Vaccinia Virus, in Patients With Peritoneal Carcinomatosis

The purpose of this study is to determine whether GL-ONC1, an attenuated vaccinia virus, is safe when administered to patients with peritoneal carcinomatosis via an infusion within the abdominal cavity through an implanted catheter. The study seeks also to arrive at a recommended dose and schedule for future investigations, evidence of anti-tumor activity, detection of virus in body fluids, analysis of viral delivery to tumor and normal cells, and to evaluate if there is an antibody response to vaccinia virus.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Peritoneal carcinomatosis includes a variety of tumors with extensive metastasis throughout the peritoneal cavity (inside surface of the abdomen) and can be found with gall bladder, liver, colon, appendix, ovarian, pancreas, mesothelioma, pseudomyxoma peritonei, rectal, small bowel and stomach cancers. It broadly includes multiple tumors that develop in and line the peritoneal abdominal cavity and linings. These tumors may be difficult to completely remove surgically and may recur despite conventional systemic chemotherapy, thereby resulting in poor patient outcomes. In preclinical studies, GL-ONC1, an oncolytic vaccinia virus, has shown the ability to preferentially locate, colonize and destroy tumor cells in more than 30 different human tumors. A Phase I clinical study focusing on the safety and tolerability of GL-ONC1 intravenously administered to patients with a variety of solid tumor entities has shown that GL-ONC1 is well-tolerated at therapeutic dose levels, with documented evidence of antitumor activity. This additional Phase I/II study seeks to evaluate GL-ONC1 administered repetitively every 4 weeks up to 4 cycles via infusion using an implanted catheter in the peritoneal cavity. In Phase I, patients will be individually assessed for safety and dose limiting toxicity. The study aims of Phase II portion are continued collection of safety information to better define the tolerability of GL-ONC1, as well as viral replication and the action or effect of GL-ONC1 in humans at the selected dose level and dosing schedule for future trials. Throughout both phases of the study, anti-tumor effects will be evaluated.

Study Type

Interventional

Enrollment (Actual)

9

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Tuebingen, Germany, D-72076
        • University Hospital Tuebingen

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Diagnosis of histologically or cytologically documented, advanced stage of peritoneal carcinomatosis that is refractory to standard therapy, exhibiting a likely survival of > 4 months as being judged clinically.
  2. Evidence of measurable disease.
  3. Age ≥ 18 years.
  4. ECOG (Eastern Cooperative Oncology Group Performance Status) ≤ 2.

  5. Required baseline laboratory data include:

    • Absolute neutrophil count (ANC) ≥ 1.5 × 109/L.
    • Platelets ≥ 75 ×109/L
    • Haemoglobin ≥ 9.5 g/dL
    • Serum creatinine ≤ 2 × upper limit of normal(ULN)
    • Total Bilirubin ≤ 5 × ULN
    • AST/ALT ≤ 7.5 × ULN
    • Negative pregnancy test for females of childbearing potential
    • Serum albumin ≥ 2.5 g/dL.
    • If serum albumin level is < 2.5/dL,albumin substitution should take place until the threshold of ≥ 2.5 g/dL.
  6. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, implantation of the indwelling peritoneal catheter, as well as the respective drainage procedures.
  7. All patients must agree to use highly effective contraception.

Exclusion Criteria:

  1. Patients exhibiting objective evidence at baseline of brain metastases are excluded from participating.
  2. Pregnant or breast-feeding women.
  3. Primary tumors and metastases to tissues/organs which, under clinical judgment, will likely hinder survival for at least the next 4 months.
  4. Patients with fever, any active immunosuppressive systemic infection or a suppressed immune system, including known HIV, as assessed within 14 days prior to study enrolment.
  5. Concurrent vaccination or immunotherapy for 28 days before study therapy and during study treatment.
  6. Patients on immunosuppressive therapy or with immune system disorders, including autoimmune diseases. Concurrent steroid use of not more than an equivalent of 20 mg/day prednisolone is allowed.
  7. Prior splenectomy.
  8. Previous organ transplantation.
  9. Fully therapeutic coagulation therapy that does not allow the intraperitoneal insertion of a permanent catheter.
  10. Patients with clinically significant dermatological disorders(e.g., eczema or psoriasis), any skin lesions or ulcers, any history of atopic dermatitis, or any history of Darier's disease (Keratosis Follicularis).
  11. Clinically significant cardiac disease (New York Heart Association, Class III or IV: see Appendix 10)
  12. Known allergy to ovalbumin or other egg products.
  13. Concurrent use of antiviral agents active against vaccinia virus.
  14. Prior gene therapy treatment or prior therapy with cytolytic virus of any type.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Determine safety of administering GL-ONC1 intraperitoneally by the evaluation of the number of patients experiencing Adverse Events (type, frequency, and severity)
Time Frame: Change from baseline over 24 hours, on days 2, 3, 4,5,6, 7 post treatment (Cycle 1) and change from baseline for Cycles 2- 4 CX/Days 1, 2, 3, 5, 8 post-treatment. Each cycle is 4 weeks and treatment will occur for a total of 4 cycles.
The safety of GL-ONC1 will be assessed by the evaluation of the type, frequency, and severity of adverse events (AEs), changes in laboratory tests (haematological, chemistry, urinary), immunogenicity and physical examination
Change from baseline over 24 hours, on days 2, 3, 4,5,6, 7 post treatment (Cycle 1) and change from baseline for Cycles 2- 4 CX/Days 1, 2, 3, 5, 8 post-treatment. Each cycle is 4 weeks and treatment will occur for a total of 4 cycles.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Dose Level and Dose Schedule
Time Frame: End of Phase I (at 18 mo.), at monthly treatments, and after study completion (expected at 36 mo.)
Determination of recommended dose and schedule for phase II portion of trial and future investigations by analysis of safety and efficacy data
End of Phase I (at 18 mo.), at monthly treatments, and after study completion (expected at 36 mo.)
Detection of Anti-tumor Activity
Time Frame: Tumor imaging [pre-study, mid-term (Day 43), after last treatment (Day 106), for 1 year @ 12-week intervals for patients with stable disease/better); Tumor markers and peritoneal cytologies collected on average over 4 months
Sampling of evidence of anti-tumor activity via standard imaging practices, viral delivery to tumor and normal cells, and immune response activity.
Tumor imaging [pre-study, mid-term (Day 43), after last treatment (Day 106), for 1 year @ 12-week intervals for patients with stable disease/better); Tumor markers and peritoneal cytologies collected on average over 4 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Genelux GmbH

Investigators

  • Principal Investigator: Ulrich M. Lauer, Prof. Dr. med., University Hospital Tuebingen
  • Principal Investigator: Michael Bitzer, Prof.Dr.med., University Hospital Tuebingen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2012

Primary Completion (ACTUAL)

September 1, 2014

Study Completion (ACTUAL)

September 1, 2014

Study Registration Dates

First Submitted

September 20, 2011

First Submitted That Met QC Criteria

September 27, 2011

First Posted (ESTIMATE)

September 29, 2011

Study Record Updates

Last Update Posted (ESTIMATE)

March 10, 2015

Last Update Submitted That Met QC Criteria

March 9, 2015

Last Verified

March 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Genelux - PO2
  • 2010-022680-35 (EUDRACT_NUMBER)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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