Head and Neck Cancer
Conditions
Keywords
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
Brief summary
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.
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.
Interventions
BIOLOGICALIL-12
Sponsors
National Cancer Institute (NCI)
Dana-Farber Cancer Institute
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is a non-randomize phase I/II where patients are directly assigned treatment.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) [Phase I] | 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] | 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] | 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
| Measure | Time frame | Description |
|---|---|---|
| Time to Progressive Disease (TTP) [Phase III] | 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] | 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] | 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. |
Countries
United States
Outcome results
None listed