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

Primary Purpose

Peritoneal Carcinomatosis

Status

Completed

Phase

Phase 1

Locations

Germany

Study Type

Interventional

Intervention

GL-ONC1

About this trial

This is an interventional treatment trial for Peritoneal Carcinomatosis focused on measuring oncolytic virus, oncolytic, GL-ONC1, Vaccinia, Vaccinia virus, Genelux, Genelux GmbH, peritoneal, peritoneal carcinomatosis, cancer, abdominal cancer, imaging

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.
Evidence of measurable disease.
Age ≥ 18 years.
ECOG (Eastern Cooperative Oncology Group Performance Status) ≤ 2.
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.
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.
All patients must agree to use highly effective contraception.

Exclusion Criteria:

Patients exhibiting objective evidence at baseline of brain metastases are excluded from participating.
Pregnant or breast-feeding women.
Primary tumors and metastases to tissues/organs which, under clinical judgment, will likely hinder survival for at least the next 4 months.
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.
Concurrent vaccination or immunotherapy for 28 days before study therapy and during study treatment.
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.
Prior splenectomy.
Previous organ transplantation.
Fully therapeutic coagulation therapy that does not allow the intraperitoneal insertion of a permanent catheter.
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).
Clinically significant cardiac disease (New York Heart Association, Class III or IV: see Appendix 10)
Known allergy to ovalbumin or other egg products.
Concurrent use of antiviral agents active against vaccinia virus.
Prior gene therapy treatment or prior therapy with cytolytic virus of any type.

Sites / Locations

University Hospital Tuebingen

Outcomes

Primary Outcome Measures

Determine safety of administering GL-ONC1 intraperitoneally by the evaluation of the number of patients experiencing Adverse Events (type, frequency, and severity)

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

Secondary Outcome Measures

Dose Level and Dose Schedule

Determination of recommended dose and schedule for phase II portion of trial and future investigations by analysis of safety and efficacy data

Detection of Anti-tumor Activity

Sampling of evidence of anti-tumor activity via standard imaging practices, viral delivery to tumor and normal cells, and immune response activity.

Full Information

NCT ID

NCT01443260

First Posted

September 20, 2011

Last Updated

March 9, 2015

Sponsor

Genelux GmbH

1. Study Identification

Unique Protocol Identification Number

NCT01443260

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2014

Overall Recruitment Status

Completed

Study Start Date

February 2012 (undefined)

Primary Completion Date

September 2014 (Actual)

Study Completion Date

September 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Genelux GmbH

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Peritoneal Carcinomatosis

Keywords

oncolytic virus, oncolytic, GL-ONC1, Vaccinia, Vaccinia virus, Genelux, Genelux GmbH, peritoneal, peritoneal carcinomatosis, cancer, abdominal cancer, imaging

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

9 (Actual)

8. Arms, Groups, and Interventions

Intervention Type

Biological

Intervention Name(s)

GL-ONC1

Intervention Description

A genetically-engineered vaccinia virus administered via intraperitoneal infusion through an indwelling catheter every 4 weeks for 4 cycles.

Primary Outcome Measure Information:

Title

Determine safety of administering GL-ONC1 intraperitoneally by the evaluation of the number of patients experiencing Adverse Events (type, frequency, and severity)

Description

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.

Secondary Outcome Measure Information:

Title

Dose Level and Dose Schedule

Description

Determination of recommended dose and schedule for phase II portion of trial and future investigations by analysis of safety and efficacy data

Time Frame

End of Phase I (at 18 mo.), at monthly treatments, and after study completion (expected at 36 mo.)

Title

Detection of Anti-tumor Activity

Description

Sampling of evidence of anti-tumor activity via standard imaging practices, viral delivery to tumor and normal cells, and immune response 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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Evidence of measurable disease. Age ≥ 18 years. ECOG (Eastern Cooperative Oncology Group Performance Status) ≤ 2. 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. 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. All patients must agree to use highly effective contraception. Exclusion Criteria: Patients exhibiting objective evidence at baseline of brain metastases are excluded from participating. Pregnant or breast-feeding women. Primary tumors and metastases to tissues/organs which, under clinical judgment, will likely hinder survival for at least the next 4 months. 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. Concurrent vaccination or immunotherapy for 28 days before study therapy and during study treatment. 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. Prior splenectomy. Previous organ transplantation. Fully therapeutic coagulation therapy that does not allow the intraperitoneal insertion of a permanent catheter. 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). Clinically significant cardiac disease (New York Heart Association, Class III or IV: see Appendix 10) Known allergy to ovalbumin or other egg products. Concurrent use of antiviral agents active against vaccinia virus. Prior gene therapy treatment or prior therapy with cytolytic virus of any type.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ulrich M. Lauer, Prof. Dr. med.

Organizational Affiliation

University Hospital Tuebingen

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Michael Bitzer, Prof.Dr.med.

Organizational Affiliation

University Hospital Tuebingen

Official's Role

Principal Investigator

Facility Information:

Facility Name

University Hospital Tuebingen

City

Tuebingen

ZIP/Postal Code

D-72076

Country

Germany

12. IPD Sharing Statement

Citations:

PubMed Identifier

29773661

Citation

Lauer UM, Schell M, Beil J, Berchtold S, Koppenhofer U, Glatzle J, Konigsrainer A, Mohle R, Nann D, Fend F, Pfannenberg C, Bitzer M, Malek NP. Phase I Study of Oncolytic Vaccinia Virus GL-ONC1 in Patients with Peritoneal Carcinomatosis. Clin Cancer Res. 2018 Sep 15;24(18):4388-4398. doi: 10.1158/1078-0432.CCR-18-0244. Epub 2018 May 17.

Results Reference

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

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