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

This study has been completed.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Robert I. Haddad, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT00004070
First received: December 10, 1999
Last updated: April 19, 2017
Last verified: April 2017
  Purpose
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.

Condition Intervention Phase
Head and Neck Cancer
Biological: IL-12
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Intervention Model Description:
This is a non-randomize phase I/II where patients are directly assigned treatment.
Masking: No masking
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • 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.

  • 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).

  • 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.


Secondary Outcome Measures:
  • 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).


  • 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.

  • 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.


Enrollment: 7
Actual Study Start Date: July 1999
Study Completion Date: December 2000
Primary Completion Date: November 2000 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.
  Eligibility

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

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00004070

Locations
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Dana-Farber Cancer Institute
National Cancer Institute (NCI)
Investigators
Study Chair: A. Dimitrios Colevas, MD NCI-Investigational Drug Branch
  More Information

Responsible Party: Robert I. Haddad, MD, Haddad, Robert MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT00004070     History of Changes
Other Study ID Numbers: 99-081
P30CA006516 ( US NIH Grant/Contract Award Number )
VALENTIS-DFCI-99081
NCI-G99-1578
CDR0000067274 ( Other Identifier: Other )
Study First Received: December 10, 1999
Last Updated: April 19, 2017
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by Dana-Farber Cancer Institute:
recurrent metastatic squamous neck cancer with occult primary
metastatic squamous neck cancer with occult primary squamous cell carcinoma
stage III squamous cell carcinoma of the lip and oral cavity
stage IV squamous cell carcinoma of the lip and oral cavity
recurrent squamous cell carcinoma of the lip and oral cavity
stage III squamous cell carcinoma of the oropharynx
stage IV squamous cell carcinoma of the oropharynx
recurrent squamous cell carcinoma of the oropharynx
stage III squamous cell carcinoma of the nasopharynx
stage IV squamous cell carcinoma of the nasopharynx
recurrent squamous cell carcinoma of the nasopharynx
stage III squamous cell carcinoma of the hypopharynx
stage IV squamous cell carcinoma of the hypopharynx
recurrent squamous cell carcinoma of the hypopharynx
stage III squamous cell carcinoma of the larynx
stage IV squamous cell carcinoma of the larynx
recurrent squamous cell carcinoma of the larynx
stage III squamous cell carcinoma of the paranasal sinus and nasal cavity
stage IV squamous cell carcinoma of the paranasal sinus and nasal cavity
recurrent squamous cell carcinoma of the paranasal sinus and nasal cavity

Additional relevant MeSH terms:
Carcinoma, Squamous Cell
Head and Neck Neoplasms
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Squamous Cell
Neoplasms by Site
Interleukin-12
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents

ClinicalTrials.gov processed this record on April 21, 2017