Safety Study of Modified Vaccinia Virus to Cancer

December 23, 2015 updated by: David Bartlett

A Phase I Dose-escalation Trial of vvDD-CDSR (Double-deleted Vaccinia Virus Plus CD/ SMR) Administered by Intratumoral Injection or Intravenous Injection

The purpose of this study is to determine the safety and maximum tolerated dose from injecting this vaccinia virus into tumors or infusion.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a Phase I, open-label, single dose, dose-escalation trial in subjects with melanoma, breast cancer, or head and neck squamous cell cancer, liver, colorectal or pancreatic adenocarinoma. The intratumoral subjects will be stratified into 2 groups. Group A includes those who have been vaccinated with vaccinia virus. A history of vaccination and a scar at vaccination site is required. Group B subjects will include those who have not been vaccinated. It is expected that the toxicity profile will be quite different between those who have been vaccinated previously with vaccinia virus and therefore subjects will be stratified separately in this Phase I trial. All subjects who have refractory tumors will receive treatment at one of five dose levels in a single dose sequential dose-escalating design. Eligible subjects will receive 1 treatment of vvDD-CDSR. A dose can be divided between 1-3 lesions. The sum total of the maximal diameters of the lesion(s) to be injected must be < 10cm.

Once the MTD and/or MFD has been defined in the vaccinated I.T. arm described above, additional subject may be enrolled at one dose level lower than the MTD/MFD and the I.V. infusion phase may begin. Patients enrolled in the IV infusion arm will receive a single administration of vvDD-CDSR at one of three dose levels in a sequential dose-escalating design.

Study Type

Interventional

Enrollment (Actual)

26

Phase

  • 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

  • United States
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15232
        • University of Pittsburgh Cancer Institute

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:

  • Greater than 18 years of age
  • Histologically-confirmed cancer that has progressed despite standard therapy. They must have one of the following tumor-types: melanoma, breast cancer, or head and neck squamous cell cancer, liver, colorectal or pancreatic
  • Cancer is not surgically curable
  • Karnofsky Performance Status (KPS) of > 70 (See Appendix B)
  • Anticipated survival of at least 16 weeks
  • If sexually-active, willingness to use condoms for 3 months following study treatment with vvDD-CDSR
  • The ability to understand and willingness to sign a written informed consent
  • Able to comply with study procedures and follow-up examinations
  • Adequate bone marrow function: WBC > 3,500 and <50,000 cells/mm3, ANC > 1,500 cells/mm3, hemoglobin > 10 g/dL, and platelet count > 150,000 cells/mm3
  • Adequate renal function: serum creatinine level ≤ 1.2 x ULN

Exclusion Criteria:

  • Pregnant or nursing an infant
  • Active viral infection (including HIV, Hepatitis B and C)
  • Systemic corticosteroid or other immunosuppressive medication use within 4 weeks of the treatment
  • Clinically significant active infection or uncontrolled medical condition (e.g., pulmonary, neurological, cardiovascular, gastrointestinal, genitourinary) considered high risk for investigational new drug treatment
  • Significant immunodeficiency (e.g. due to underlying illness and/ or medication) in subject or household contacts
  • History of eczema requiring systemic therapy
  • Unstable cardiac disease which includes but is not limited to: Any of the following within 6 months prior to study entry: MI, unstable angina, congestive heart failure, myocarditis, arrhythmias diagnosed and requiring medication, or any clinically-significant change in cardiac status
  • Target tumor(s) adherent to a major vascular structure (e.g. carotid artery)
  • Subjects who have received radiation, chemotherapy or other potentially immunosuppressive therapy in 4 weeks prior to study screening
  • Clinically significant and/or rapidly accumulating ascites, peri-cardial and/or pleural effusions
  • Experienced a severe systemic reaction or side-effect as a result of a previous smallpox vaccination
  • Subjects with household contacts who are pregnant or nursing an infant, children < 5 years old, have history of eczema that at some stage has required systemic therapy, or have a significant immunodeficiency due to underlying illness (e.g. HIV) and/or medication (e.g. systemic corticosteroids) will be excluded unless alternate living arrangements can be made during the subject's active dosing period and for three weeks following the last dose of study medication
  • Inability or unwillingness to give informed consent.
  • CD4 T cell count < 350 per µL blood

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: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: A
Subjects who have been vaccinated with vaccinia virus (small pox)and will receive vvDD-CDSR by intratumoral injection
Biological: Vaccinia virus (vvDD-CDSR)

Eligible subjects will receive 1 treatment of vvDD-CDSR. A dose can be divided between 1-3 lesions. The sum total of the maximal diameters of the lesion(s) to be injected must be < 10cm.

Cohort 1: 3 x 10e7 p.f.u. Cohort 2: 1 x 10e8 p.f.u. Cohort 3: 3 x 10e8 p.f.u. Cohort 4: 1 x 10e9 p.f.u. Cohort 5: 3 x 10e9 p.f.u.

Biological: Vaccinia virus (vvDD-CDSR)

Eligible subjects will receive 1 infusion of vvDD-CDSR.

Cohort 1: 3 x 10e8 p.f.u; Cohort 2: 1 x 10e9 p.f.u.; Cohort 3: 3 x 10e9 p.f.u.
Experimental: B
Subjects will include those who have not been vaccinated with vaccinia virus (small pox)and will receive vvDD-CDSR by intratumoral injection.
Biological: Vaccinia virus (vvDD-CDSR)

Eligible subjects will receive 1 treatment of vvDD-CDSR. A dose can be divided between 1-3 lesions. The sum total of the maximal diameters of the lesion(s) to be injected must be < 10cm.

Cohort 1: 3 x 10e7 p.f.u. Cohort 2: 1 x 10e8 p.f.u. Cohort 3: 3 x 10e8 p.f.u. Cohort 4: 1 x 10e9 p.f.u. Cohort 5: 3 x 10e9 p.f.u.

Biological: Vaccinia virus (vvDD-CDSR)

Eligible subjects will receive 1 infusion of vvDD-CDSR.

Cohort 1: 3 x 10e8 p.f.u; Cohort 2: 1 x 10e9 p.f.u.; Cohort 3: 3 x 10e9 p.f.u.
Experimental: C
Subjects will be those who have been vaccinated with vaccinia virus (small pox)and will be receiving the vvCD-CDSR via intravenous infusion
Biological: Vaccinia virus (vvDD-CDSR)

Eligible subjects will receive 1 treatment of vvDD-CDSR. A dose can be divided between 1-3 lesions. The sum total of the maximal diameters of the lesion(s) to be injected must be < 10cm.

Cohort 1: 3 x 10e7 p.f.u. Cohort 2: 1 x 10e8 p.f.u. Cohort 3: 3 x 10e8 p.f.u. Cohort 4: 1 x 10e9 p.f.u. Cohort 5: 3 x 10e9 p.f.u.

Biological: Vaccinia virus (vvDD-CDSR)

Eligible subjects will receive 1 infusion of vvDD-CDSR.

Cohort 1: 3 x 10e8 p.f.u; Cohort 2: 1 x 10e9 p.f.u.; Cohort 3: 3 x 10e9 p.f.u.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Determine the maximally tolerated dose (MTD) and/or maximum-feasible dose (MFD) and Safety of vvDD-CDSR administered by intratumoral (I.T.) injection and intravenous (I.V.) infusion.
Time Frame: 28 days
28 days

Secondary Outcome Measures

Outcome Measure
Time Frame
Replication/pharmacokinetics of vvDD-CDSR
Time Frame: 28 days
28 days
Immune response to vvDD-CDSR and to the tumor following administration
Time Frame: 28 days
28 days
Antitumoral efficacy of vvDD-CDSR
Time Frame: 28 days
28 days

Collaborators and Investigators

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

Sponsor

David Bartlett

Investigators

  • Principal Investigator: Herbert J. Zeh, MD, PhD, University Of Pittsburgh

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

May 1, 2008

Primary Completion (Actual)

January 1, 2013

Study Completion (Actual)

July 1, 2014

Study Registration Dates

First Submitted

December 13, 2007

First Submitted That Met QC Criteria

December 14, 2007

First Posted (Estimate)

December 17, 2007

Study Record Updates

Last Update Posted (Estimate)

December 28, 2015

Last Update Submitted That Met QC Criteria

December 23, 2015

Last Verified

December 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 06-041

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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