Biological Vaccine: Semi-allogeneic Human Fibroblasts (MRC-5) Transfected With DNA

NCT02211027 | Withdrawn Phase 1 DMC

• 1 other identifier: 13-160
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 3

Brief Summary

Hypothesis The incidence of toxicity in patients receiving the tumor DNA-transfected fibroblast vaccine will be acceptably low and the immunologic response rate sufficiently high to warrant further study of this therapy The study of the vaccine will proceed in two stages after the method of Simon (102). In the first stage, 15 patients will be accrued and treated. If two or fewer objective immunologic responses occur, the study will be terminated. If 3 or more responses are observed, the study will proceed to the second stage, accruing an additional 22 patients. If the second stage is complete and a total of 9 or more immunologic responses are observed among the 37 patients treated, the treatment response rate for the vaccine will be considered high enough to warrant further study. Conversely, if the evaluation of the vaccine concludes at the first stage, or if 8 or fewer total immunologic responses occur after completing the second stage, the vaccine will not be considered for further study.

Conditions

Head and Neck Squamous Cell Carcinoma (HNSCC)

Keywords

Squamous Cell Carcinoma; Head & Neck Cancer; Vaccine; Carcinoma; Immunization; Autologous Tumor

Outcome Measures

Primary Outcomes (1)

• Immunization Safety

  Toxicity will be monitored continuously from the first vaccination through the 6 month post follow up study visit for each subject. Patients will have a follow-up visit at 1 week after last vaccination (day 29, off treatment), at 1 month, 3 months and 6 months after last vaccination or after removal from study or until death, whichever occurs first. After the 6 month follow-up visit, subjects will be followed for survival only (no additional clinical trial site visits). Patients removed from study for unacceptable adverse event(s) will be followed until resolution or stabilization of the adverse event. All subjects should be enrolled within 2 years and follow up studies complete within 3 years.

  2.5 years

Secondary Outcomes (1)

• Immunologic Response Rate to the the tumor DNA-transfected fibroblast vaccine

  2.5 years

Other Outcomes (1)

• Immune competence

  2.5 years

Study Arms (1)

Vaccine

EXPERIMENTAL

The vaccine is composed of lethally irradiated semi-allogenic human fibroblasts (MRC-5) transfected with genomic tumor DNA from the patients own tumor.

Biological: Semi-allogenic human fibroblast (MRC-5) transfected with DNA

Interventions

Semi-allogenic human fibroblast (MRC-5) transfected with DNA BIOLOGICAL

Each vaccination consists of up to 1 x 10e7 (not less than 7 x 10e6) DNA-transfected irradiated fibroblasts. Each vaccination will be administered intradermally using a 1 mL syringe and a 25 gauge needle.The first immunization will be administered at least 12 weeks after surgery or completion of adjuvant chemotherapy and/or radiotherapy.Three additional vaccines will be administered once a week for a total of four vaccines. Patients will have vaccinations administered at 4 different sites as follows: Site #1: Right arm Site #2: Left arm Site #3: Right thigh Site #4: Left thigh. Approximately equal numbers of transfected fibroblasts will be administered at each site.

Vaccine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pathological stage I-IVa HNSCC
• The subject must have a complete removal of the primary HNSCC lesion with negative gross and microscopic margins. Documentation of margins by frozen sections at surgery is recommended. Patients who have already had surgery and have available banked tumor samples can be enrolled AFTER surgery.
• At least 18 years of age.
• Karnofsky performance status \>/= 70
• Adequate hematologic function:
• Absolute neutrophil count \> 1,000/mm3
• Absolute lymphocyte count \> 1,000/mm3
• Hemoglobin \> 9 g/dL
• Platelets \> 100,000/mm3
• Liver function tests:
• Bilirubin (total) \< /=1.7 mg/dL
• Alkaline phosphatase \< 252 u/L
• SGOT \< 108 u/L
• Kidney profile:
• Serum electrolytes

You may not qualify if:

• Patients will be EXCLUDED from participation in the study if any of the following apply:
• A significant history or current evidence of cardiac disease including, but not limited to: congestive heart failure, coronary artery disease, angina pectoris, uncontrolled hypertension, serious arrhythmias or myocardial infarction within the previous six months.
• Evidence of ongoing or active infection requiring antibiotic therapy.
• Active intracranial metastases. Patients with previously resected intracranial disease and/or previously irradiated intracranial metastases that have been clinically stable for four weeks are eligible.
• Pregnant or lactating women. Pregnant women are excluded from this study. Women of childbearing potential must have a negative pregnancy test per standard of care prior to the surgery for tumor removal. A second pregnancy test must be performed 7 days prior to the first vaccination and must be negative. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother, breastfeeding should be discontinued if the mother is treated on study.
• Patients requiring systemic corticosteroids (unless patients have had no corticosteroids within 4 weeks prior to start of study).
• Autoimmune disease including, but not limited to, rheumatoid arthritis, systemic lupus erythematous, multiple sclerosis, or ankylosing spondylitis.
• Patients who have post-obstructive pneumonia or other serious infection at the time of registration or other serious underlying medical condition that would impair the ability of the patient to receive protocol treatment.
• No prior malignancy is allowed except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the patient has been disease-free for at least 5 years prior to registration.
• Uncontrolled intercurrent illness including, but not limited to psychiatric illness/social situations that would limit compliance with study requirements.
• HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study. HIV testing will be performed in patients receiving combination anti-retroviral therapy when indicated per medical records review.

Sponsors & Collaborators

• Robert Ferris: lead
• Immune Cell Therapy Inc.: collaborator

Study Sites (3)

University of Pittsburgh Medical Center Presbyterian Hospital

Pittsburgh, Pennsylvania, 15213, United States

Location

University of Pittsburgh Cancer Institute-Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

University Of Pittsburgh Medical Center- Shadyside Hospital

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Carcinoma, Squamous Cell; Head and Neck Neoplasms; Carcinoma

Interventions

DNA

Condition Hierarchy (Ancestors)

Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Squamous Cell

Intervention Hierarchy (Ancestors)

Nucleic Acids; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Robert L Ferris, MD

  Professor of Otolaryngology, Eye & Ear Institute of the University of Pittsburgh Medical Center.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Otolaryngology

Study Record Dates

• First Submitted: July 16, 2014
• First Posted: August 7, 2014
• Study Start: September 1, 2016
• Primary Completion: October 1, 2017
• Study Completion (Estimated): December 1, 2028
• Last Updated: September 7, 2017

Record last verified: 2017-09

Locations

US (3)