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Safety Study of Modified Vaccinia Virus to Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00574977
Recruitment Status : Completed
First Posted : December 17, 2007
Last Update Posted : December 28, 2015
Sponsor:
Information provided by (Responsible Party):
David Bartlett, University of Pittsburgh

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

Condition or disease Intervention/treatment Phase
Melanoma Breast Cancer Head and Neck Squamous Cell Cancer Liver Cancer Colorectal Cancer Pancreatic Adenocarcinoma Biological: Vaccinia virus (vvDD-CDSR) Phase 1

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 26 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Dose-escalation Trial of vvDD-CDSR (Double-deleted Vaccinia Virus Plus CD/ SMR) Administered by Intratumoral Injection or Intravenous Injection
Study Start Date : May 2008
Actual Primary Completion Date : January 2013
Actual Study Completion Date : July 2014

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma
MedlinePlus related topics: Viral Infections

Arms and Interventions
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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.
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.
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 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.


Outcome Measures
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Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. Replication/pharmacokinetics of vvDD-CDSR [ Time Frame: 28 days ]
  2. Immune response to vvDD-CDSR and to the tumor following administration [ Time Frame: 28 days ]
  3. Antitumoral efficacy of vvDD-CDSR [ Time Frame: 28 days ]

Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00574977


Locations
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United States, Pennsylvania
University of Pittsburgh Cancer Institute
Pittsburgh, Pennsylvania, United States, 15232
Sponsors and Collaborators
David Bartlett
Investigators
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Principal Investigator: Herbert J. Zeh, MD, PhD University of Pittsburgh
More Information
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Responsible Party: David Bartlett, Chief, Division of Surgical Oncology, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT00574977    
Other Study ID Numbers: 06-041
First Posted: December 17, 2007    Key Record Dates
Last Update Posted: December 28, 2015
Last Verified: December 2015
Keywords provided by David Bartlett, University of Pittsburgh:
vaccinia
virus
tumor
melanoma
breast cancer
 squamous cell cancer
colorectal
liver
pancreatic
adenocarcinoma
Additional relevant MeSH terms:
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Vaccinia
Melanoma
Adenocarcinoma
Neoplasms, Squamous Cell
Carcinoma, Squamous Cell
Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
 Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Carcinoma
Neoplasms, Glandular and Epithelial
Poxviridae Infections
DNA Virus Infections
Virus Diseases
Infections