Safety Study of Modified Vaccinia Virus to Cancer

NCT ID: NCT00574977

Last Updated: 2015-12-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

26 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-05-31

Study Completion Date

2014-07-31

Brief Summary

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

Detailed Description

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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.

Conditions

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Melanoma Breast Cancer Head and Neck Squamous Cell Cancer Liver Cancer Colorectal Cancer Pancreatic Adenocarcinoma

Keywords

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vaccinia virus tumor melanoma breast cancer squamous cell cancer colorectal liver pancreatic adenocarcinoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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A

Subjects who have been vaccinated with vaccinia virus (small pox)and will receive vvDD-CDSR by intratumoral injection

Group Type EXPERIMENTAL

Vaccinia virus (vvDD-CDSR)

Intervention Type BIOLOGICAL

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.

B

Subjects will include those who have not been vaccinated with vaccinia virus (small pox)and will receive vvDD-CDSR by intratumoral injection.

Group Type EXPERIMENTAL

Vaccinia virus (vvDD-CDSR)

Intervention Type BIOLOGICAL

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.

C

Subjects will be those who have been vaccinated with vaccinia virus (small pox)and will be receiving the vvCD-CDSR via intravenous infusion

Group Type EXPERIMENTAL

Vaccinia virus (vvDD-CDSR)

Intervention Type BIOLOGICAL

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.

Interventions

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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.

Intervention Type 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.

Intervention Type 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.

Intervention Type BIOLOGICAL

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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David Bartlett

OTHER

Sponsor Role lead

Responsible Party

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David Bartlett

Chief, Division of Surgical Oncology

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Herbert J. Zeh, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

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University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, United States

Site Status

Countries

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United States

Other Identifiers

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06-041

Identifier Type: -

Identifier Source: org_study_id