Gene Therapy in Treating Patients With Unresectable, Recurrent, or Refractory Head and Neck Cancer

April 19, 2017 updated by: Robert I. Haddad, MD, Dana-Farber Cancer Institute

A Multi-Center, Open-Label, Multiple Administration, Rising Dose Study of the Safety, Tolerability, and Efficacy of IL-12 Gene Medicine in Patients With Unresectable or Recurrent/Refractory Squamous Cell Carcinoma of the Head and Neck (SCCHN)

Participant with squamous cell cancer of head and neck are invited to participate in this study. In this study the investigators will be Inserting the gene for interleukin-12 into a person's cancer cells with the anticipation to make the body build an immune response to kill more tumor cells.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This is a Phase I/II trial to study the effectiveness of gene therapy in treating patients who have unresectable, recurrent, or refractory head and neck cancer.

Study Type

Interventional

Enrollment (Actual)

7

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

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Medical Center
      • Boston, Massachusetts, United States, 02115
        • Dana-Farber 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:

  • Females must be non-pregnant and non-lactating and either surgically sterile (via hysterectomy or bilateral tubal ligation), at least one year post-menopausal, or using acceptable methods of contraception for the duration of the study.
  • Male subjects must be surgically sterile or using an acceptable method of contraception for the duration of the study.
  • Disease: biopsy-proven unresectable or recurrent/refractory squamoussell_eareinoma_of_the:head-and-neck-(usualLy -Stage-Di-or-IV) -
  • Tumor accessible to direct injection
  • Karnofsky performance of at least 70%
  • Life expectancy of at least three months
  • Able to give written informed consent

Exclusion Criteria:

  • Infection (concurrent or within previous 2 weeks)
  • Active or clinically-relevant viral illnesses.
  • Use of corticosteroids, high-dose non-steroidal antiinflammatory, or immunosuppressive drugs
  • Chemotherapy, radiotherapy or immunotherapy within 28 days of study entry or during the course of study
  • Respiratory disease sufficient to influence oxygenation of arterial blood
  • Active liver disease with transaminases >3 times the upper limit of normal
  • Previous history of liver disease
  • NYHA Class EU or greater heart failure
  • Serum creatinine of greater than 1.5 times the upper limit of normal
  • Polymorphonuclear neutrophilic leukocyte count <3,000/mm3
  • Platelet count <50,000/mm 3
  • Tumor involving major blood vessels or obstructing the airway
  • Previous treatment with viral-based gene therapy, recombinant DNA products, or bacterial plasmids
  • Use of an investigational drug within 30 days of screening
  • Other malignancies requiring treatment during the study
  • Scheduled surgical resection
  • History of autoimmune disease, including rheumatic disease, Crohn's disease, etc. ,
  • Known allergy to polyvinylpyrrofidone (PVP) or related products
  • History of psychiatric disabilities or seizures.

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: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: IL-12 Injection 3mg/ml [Phase I]
The dosing schedule will consist of eight injections 3 mg/ml of formulated plasmid over a seven week period.
Biological: IL-12
Other Names:
  • NFSK
  • CLMF
  • P35
  • Interleukin-12 gene
Experimental: IL-12 Injection 6mg/ml [Phase I]
The dosing schedule will consist of eight injections 6mg/ml of formulated plasmid over a seven week period.
Biological: IL-12
Other Names:
  • NFSK
  • CLMF
  • P35
  • Interleukin-12 gene
Experimental: IL-12 Injection MTD [Phase II]
The dosing schedule will consist of eight injections over a seven week period of formulated plasmid at the MTD established in the phase I portion.
Biological: IL-12
Other Names:
  • NFSK
  • CLMF
  • P35
  • Interleukin-12 gene

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum Tolerated Dose (MTD) [Phase I]
Time Frame: Assessed during therapy up to 7 weeks.
The MTD of IL-12 gene medicine is determined by the number of participants who experience a dose limiting toxicity (DLT). The MTD is defined as the highest dose at which fewer than one-third of patients experience a DLT. If no DLTs are observed in the two dose levels planned then evaluation of a third escalation will be considered. If the MTD is not reached, the dose selected for use in the phase II portion will be defined as the maximum volume that can be reasonably and safely injected into the tumor.
Assessed during therapy up to 7 weeks.
Dose Limiting Toxicity (DLT) [Phase I]
Time Frame: Assessed during therapy up to 7 weeks.
A DLT was defined as grade 4 hematologic toxicity greater than 5 days duration or grade 3 or higher non-hematologic toxicity based on NCI common toxicity criteria (CTCAEv2).
Assessed during therapy up to 7 weeks.
Grade 3-4 Toxicity Rate [Phase II]
Time Frame: Assessed until last scheduled on-study visit up to visit 12/day 112.
All Grade 3-4 events based on CTCAEv2 as reported on case report forms.
Assessed until last scheduled on-study visit up to visit 12/day 112.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to Progressive Disease (TTP) [Phase III]
Time Frame: Measurement by CT occurs up to the earliest of progression, death or 4 months after enrollment of last patient.

Time to progression based on the Kaplan-Meier method is defined as the duration of time from study entry to documented first observation of progressive disease (PD).

Time to progression based on the Kaplan-Meier method is defined as the duration of time from study entry to documented first observation of progressive disease (PD).
Measurement by CT occurs up to the earliest of progression, death or 4 months after enrollment of last patient.
Response [Phase II]
Time Frame: Measurement by CT occurs up to visit 12/day 112.
Best response on treatment classifies patients into 4 groups: complete response (CR) is complete disappearance of all signs, symptoms, biochemical and radiographic evidence of tumor for a minimum of 1 month; partial response (PR) is >/=50% decreases in tumor area for at least 4 weeks without an increase in size of other lesions of >25% or appearance of new lesions; progressive disease (PD) is >50% increase in size of any lesion present at baseline or after response, or appearance of a new lesion; and stable disease (SD) is neither PR or better nor PD.
Measurement by CT occurs up to visit 12/day 112.
Overall Survival (OS) [Phase II]
Time Frame: Measurement by CT occurs up to the earliest of progression, death or 4 months after enrollment of last patient.
OS is defined as the duration of time from study entry to death or date last known alive and estimated using Kaplan-Meier (KM) methods.
Measurement by CT occurs up to the earliest of progression, death or 4 months after enrollment of last patient.

Collaborators and Investigators

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

Sponsor

Dana-Farber Cancer Institute

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: A. Dimitrios Colevas, MD, NCI-Investigational Drug Branch

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 (Actual)

July 1, 1999

Primary Completion (Actual)

November 1, 2000

Study Completion (Actual)

December 1, 2000

Study Registration Dates

First Submitted

December 10, 1999

First Submitted That Met QC Criteria

June 3, 2004

First Posted (Estimate)

June 4, 2004

Study Record Updates

Last Update Posted (Actual)

April 20, 2017

Last Update Submitted That Met QC Criteria

April 19, 2017

Last Verified

April 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 99-081
  • P30CA006516 (U.S. NIH Grant/Contract)
  • VALENTIS-DFCI-99081
  • NCI-G99-1578
  • CDR0000067274 (Other Identifier: Other)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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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