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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


Phase 1/Phase 2
18 Years
N/A
Not Enrolling
Both
Oral Mucositis

Thank you

Trial Information

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.


Inclusion Criteria:



- Willing and able to understand and sign the study specific Informed Consent Form
(ICF) approved by the site's Institutional Review Board

- Males or females 18 years or older

- Recently diagnosed with pathologically-confirmed squamous cell carcinoma of the head
and neck (e.g., oral cavity, oropharynx, hypopharynx, larynx, nasopharynx, lips,
sinuses, salivary glands, unknown primary)

- Planned to receive at least two cycles of induction chemotherapy of the same regimen
consisting of cisplatin/fluorouracil (PF) or cisplatin/fluorouracil/docetaxel (PFT).
The planned CT cycles must be of the same length and must be a minimum of 14 days in
length

- Karnofsky performance score ≥ 60%

- Screening laboratory assessments:

- Hemoglobin ≥ 10g/dl

- White blood count ≥ 3500 cells/mm3

- Absolute neutrophil counts ≥ 1500 cells/ mm3

- Direct bilirubin ≤ 2x upper limit of normal (ULN)

- Serum AST and ALT ≤ 3 x ULN

- Serum creatinine ≤ 2 mg/dl

- Serum pregnancy test: negative for females of childbearing potential: A women is
considered to be of child bearing potential unless she has had a tubal ligation or is
postmenopausal (without a menstrual period for at least one year)

- Subjects of childbearing potential must agree to utilize effective contraceptive
methods of birth control during study participation and for 30 days following the
last treatment with IMP

- Have documented mouth pain during CT Cycle 1 (i.e., OMDQ question 2 score of ≥ 2
during CT Cycle 1)

Exclusion Criteria:

- Prior radiation to the head and neck

- Chemotherapy within 21 days prior to study start

- Presence of active infectious disease excluding oral candidiasis

- Current use of antibiotic rinses or troches

- Alcohol abuse syndrome; recovered alcoholics may be included

- Presence of OM (WHO Grade > 0)

- Chronic immunosuppression

- Known seropositive for HIV or hepatitis B or C

- Use of investigational agent within 30 days of signing informed consent

- Teeth extractions within 7 days prior to the start of CT administration

- Female subjects who are pregnant or nursing

- Known sensitivity to any investigational agent

- Inability to give informed consent or comply with study requirements

- Unwilling or unable to complete subject diary

- Any other clinical condition, psychiatric condition or prior therapy that, in the
opinion of the Investigator, would make the subject unsuitable for the study or
unable or to comply with follow-up visits

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject)

Outcome Measure:

Safety (Adverse Events, laboratory assessments and the presence of sAGX0085 bacteria in blood)

Outcome Description:

Up to 16 months

Outcome Time Frame:

16 months

Safety Issue:

Yes

Principal Investigator

Barbara A Murphy, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Vanderbilt-Ingram Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

AG013-ODOM-101

NCT ID:

NCT00938080

Start Date:

September 2009

Completion Date:

September 2012

Related Keywords:

  • Oral Mucositis
  • Head and Neck Neoplasms
  • Stomatitis
  • Mucositis

Name

Location

Stanford UniversityStanford, California  94305
Beth Israel Medical CenterNew York, New York  10003
Carolinas Medical CenterCharlotte, North Carolina  28232-2861
University of Illinois at ChicagoChicago, Illinois  60612
Dana Farber Cancer InstituteBoston, Massachusetts  02115
Vanderbilt Ingram Cancer CenterNashville, Tennessee  37232