A Phase 1b, Multi-center, Single Blinded, Placebo-controlled, Sequential Dose Escalation Study to Assess the Safety and Tolerability of Topically Applied AG013 in Subjects Receiving Induction Chemotherapy for the Treatment of Cancers of the Head and Neck
The purpose of this study is to investigate the safety and tolerability of AG013 in subjects
who are at risk for oral mucositis (OM) and to assess clinical efficacy of AG013 in the
reduction of signs and symptoms of OM in patients receiving induction chemotherapy for the
treatment of their head and neck cancer.
AG013 is made up of genetically modified (GM) bacteria called Lactococcus lactis (L.
lactis). Wild type L. lactis are commonly used to produce dairy products including cheeses
and milk. To make AG013, the DNA of L. lactis has been changed in the laboratory to secrete
a protein called human Trefoil Factor 1 (hTFF1). hTFF1 is normally secreted in saliva and
intestines. Trefoil factors have been shown to be important in protecting and healing
mucosal tissues, such as the tissue in the mouth, when these tissues are damaged by cancer
therapies such as chemotherapy and radiation therapy.
The proposed Phase 1b clinical trial will enroll subjects with head and neck cancer who
develop OM during their first cycle of treatment with induction chemotherapy. OM is a
painful, common toxicity of many forms of drug and radiation therapy used for the treatment
of cancer. Subjects with OM get soreness, irritation, and ulcers in the mouth and may have
difficulties eating, drinking or swallowing as a result of their cancer treatment.
During the second cycle of induction chemotherapy, eligible subjects will receive AG013 or
placebo for 14 consecutive days at a frequency of one rinse, three rinses or six rinses per
day (sequential dose escalation design).
At least 21 subjects will be enrolled in the study. For each of the three daily dose levels,
5 subjects will be assigned to AG013 (n=5) and 2 subjects will be assigned to placebo (n=2).
Throughout the study, safety will be monitored by collecting and recording Adverse Events,
laboratory assessments and the presence of sAGX0085 bacteria in blood.
An independent Data Safety Monitoring Board (DSMB) will be constituted before the enrollment
of subjects in order to review safety data from each enrollment group.
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject)
Safety (Adverse Events, laboratory assessments and the presence of sAGX0085 bacteria in blood)
Up to 16 months
Barbara A Murphy, MD
Vanderbilt-Ingram Cancer Center
United States: Food and Drug Administration
|Stanford University||Stanford, California 94305|
|Beth Israel Medical Center||New York, New York 10003|
|Carolinas Medical Center||Charlotte, North Carolina 28232-2861|
|University of Illinois at Chicago||Chicago, Illinois 60612|
|Dana Farber Cancer Institute||Boston, Massachusetts 02115|
|Vanderbilt Ingram Cancer Center||Nashville, Tennessee 37232|