Vaccine Therapy in Treating Patients With Persistent or Recurrent Cervical Cancer

PRIMARY OBJECTIVES:

I. To evaluate the tolerability, safety, and nature and degree of toxicity of ADXS11-001
(live-attenuated Listeria monocytogenes cancer vaccine ADXS11-001) by the numbers of patients
with dose-limiting toxicities (DLTs) and adverse events as assessed by the Common Terminology
Criteria for Adverse Events (CTCAE) version (v)4.0.

II. To assess the activity of ADXS11-001 for patients with persistent or recurrent carcinoma
of the cervix with the frequency of patients who survive for at least 12 months after
initiating therapy.

SECONDARY OBJECTIVES:

I. To characterize the distribution of progression-free survival and overall survival.

II. To examine the proportion of patients with objective tumor response.

TERTIARY OBJECTIVES:

I. To assess changes in clinical immunology based upon serum cytokines and to correlate any
observed changes with clinical response including progression-free survival, overall
survival, tumor response, DLTs, and adverse effects.

II. To examine associations between presence and type of high-risk human papillomavirus
(H-HPV) and measures of clinical response and serum cytokine levels.

OUTLINE:

Patients receive live-attenuated Listeria monocytogenes cancer vaccine ADXS11-001
intravenously (IV) over 30 minutes on day 1. Courses repeat every 28 days in the absence of
disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years and
then every 6 months for 3 years.

Inclusion Criteria:

- Patients must have persistent or recurrent squamous or non-squamous cell carcinoma,
adenosquamous carcinoma, or adenocarcinoma of the cervix with documented disease
progression (disease not amenable to curative therapy); histologic confirmation of the
original primary tumor is required via the pathology report

- Patient must have measurable disease as defined by Response Evaluation Criteria in
Solid Tumors (RECIST) 1.1

- Measurable disease is defined as at least one lesion that can be accurately
measured in at least one dimension (longest dimension to be recorded)

- Each lesion must be >= 10 mm when measured by computed tomography (CT), magnetic
resonance imaging (MRI), or caliper measurement by clinical exam; or >= 20 mm
when measured by chest x-ray

- Lymph nodes must be >= 15 mm in short axis when measured by CT or MRI

- Patient must have at least one 'target lesion" to be used to assess response on this
protocol as defined by RECIST 1.1

- Tumors within a previously irradiated field will be designated as 'non-target"
lesions unless progression is documented or a biopsy is obtained to confirm
persistence at least 90 days following completion of radiation therapy

- Patients must not be eligible for a higher priority Gynecologic Oncology Group (GOG)
protocol, if one exists

- In general, this would refer to any active GOG phase III or rare tumor protocol
for the same patient population

- Patients must have a GOG performance status of 0 or 1

- Recovered from effects of recent surgery, radiotherapy, or chemotherapy

- Patients should be free of active infection requiring antibiotics

- Any hormonal therapy directed at the malignant tumor must be discontinued at least one
week prior to registration

- Continuation of hormone replacement therapy is permitted

- Any other prior therapy directed at the malignant tumor, including chemotherapy,
biologic/targeted (non-cytotoxic) agents and immunologic agents, must be discontinued
at least three weeks prior to registration

- Any prior radiation therapy must be completed at least 4 weeks prior to registration

- Patients must have had one prior systemic chemotherapeutic regimen for management of
advanced, metastatic, or recurrent carcinoma of the cervix

- Chemotherapy administered concurrent with primary radiation (e.g.; weekly
cisplatin) is not counted as a systemic chemotherapy regimen for management of
advanced, metastatic, or recurrent disease; adjuvant chemotherapy given following
the completion of radiation therapy (or concurrent chemotherapy and radiation
therapy) is not counted as a systemic chemotherapy regimen for management of
advanced, metastatic, or recurrent disease (e.g.; paclitaxel and carboplatin for
up to 4 cycles)

- Patients are allowed to receive, but are not required to receive, biologic/targeted
(non-cytotoxic) therapy as part of their primary therapy and/or as part of their
therapy for advanced, metastatic, or recurrent disease (e.g., bevacizumab)

- Platelet count greater than or equal to 75,000/mcL

- Absolute neutrophil count (ANC) count greater than or equal to 1,000/mcL

- Lymphocyte count greater than or equal to 700/mcL

- Hemoglobin count greater than or equal to 9 g/dL or greater than or equal to 5.6
mmol/L

- Note: ANC, platelets, hemoglobin requirement cannot be met by the use of recent
transfusions, or growth factor support (granulocyte colony-stimulating factor
[G-CSF], erythropoietin, etc.) within 2 weeks prior to treatment initiation

- Creatinine less than or equal to 1.5 x institutional upper limit of normal (ULN) or
measured or calculated creatinine clearance greater than or equal to 50 mL/min for
subject with creatinine levels greater than 1.5 x institutional ULN; (glomerular
filtration rate [GFR] can also be used in place of creatinine or creatinine clearance
[CrCl]) (creatinine clearance should be calculated per institutional standard)

- Total bilirubin less than or equal to 1.5 x ULN

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal
to 3 x ULN

- Alkaline phosphatase less than or equal to 2.5 x ULN

- International normalized ratio (INR) or prothrombin time (PT) and activated partial
thromboplastin time (aPTT) less than or equal to 1.5 x ULN, unless patient is
receiving anticoagulant therapy as long as PT or INR is within therapeutic range of
intended use of anticoagulants

- Neuropathy (sensory and motor) less than or equal to grade 1

- Patients must have signed an approved informed consent and authorization permitting
release of personal health information

- Patients must meet pre-entry requirements as specified

- Patients of childbearing potential must have a negative serum pregnancy test prior to
the study entry and must agree to ongoing use of 2 methods of study doctor approved
birth control or abstain from heterosexual activity for the course of the study from
screening through 120 days after the last dose of study medication; patients of
childbearing potential are those who have not been surgically sterilized or have not
been free from menses for > 1 year

- Patients cannot be lactating

- Patients must be able to swallow pills

Exclusion Criteria:

- Patients who have received prior therapy with ADXS11-001

- Patients with a history of other invasive malignancies, with the exception of
non-melanoma skin cancer and other specific malignancies as noted below are excluded
if there is any evidence of other malignancy being present within the last three
years; patients are also excluded if their previous cancer treatment contraindicates
this protocol therapy

- Patients who have received prior radiotherapy to any portion of the abdominal cavity
or pelvis OTHER THAN for the treatment of cervical cancer within the last three years
are excluded

- Prior radiation for localized cancer of the breast, head and neck, or skin is
permitted provided that it was completed more than three years prior to
registration and the patient remains free of recurrent or metastatic disease

- Patients who have received prior chemotherapy for any abdominal or pelvic tumor OTHER
THAN for the treatment of cervical cancer within the last three years are excluded;
patients may have received prior adjuvant chemotherapy for localized breast cancer,
provided that it was completed more than three years prior to registration, and that
the patient remains free of recurrent or metastatic disease

- Patients with a contraindication (e.g. sensitivity/allergy) to
trimethoprim/sulfamethoxazole or ampicillin

- Patients allergic to nonsteroidal antiinflammatory drug (NSAID)

- Patients with active infection requiring systemic therapy or who are dependent on or
currently receiving antibiotics that cannot be discontinued before dosing; (Note:
subjects who discontinue an antibiotic prior to dosing must wait at least 5 half-lives
after the last dose of antibiotic before receiving any ADXS11-001 infusion)

- Patients with a diagnosis of immunodeficiency, or who are dependent on or have
received systemic steroid therapy or any other form of immunosuppressive therapy
within 7 days prior to the first dose of trial treatment with the exception of topical
corticosteroids and occasional inhaled corticosteroids, as indicated

- Patients with uncontrolled intercurrent illness including, but not limited to:

- Ongoing or active infection

- Symptomatic congestive heart failure

- Unstable angina pectoris

- Cardiac arrhythmia or

- Psychiatric illness/social situations that would limit compliance with study
requirements

- Patients with liver cirrhosis or any other impaired hepatic function as determined by
serum enzymes

- Patients known to be seropositive for human immunodeficiency virus (HIV) and/or active
hepatitis, even if liver function studies are in the eligible range

- Patients with a prior history of a splenectomy and/or sickle cell trait/disease

- Patient has implanted medical device(s) that pose a high risk for colonization and/or
cannot be easily removed (e.g., prosthetic joints, artificial heart valves,
pacemakers, orthopedic screw(s), metal plate(s), bone graft(s), or other exogenous
implant(s)); NOTE: more common devices and prosthetics which include arterial and
venous stents, dental and breast implants and venous access devices (e.g., Port-a-Cath
or Mediport) are permitted; sponsor must be contacted prior to consenting any subject
who has any other device and/or implant

- Any patient currently requiring or anticipated to require tumor necrosis factor (TNF)
blocking agent (e.g., infliximab) therapy for diagnosis of rheumatologic disease or
inflammatory bowel disease (e.g., ankylosing spondylitis, Crohn disease, plaque
psoriasis, psoriatic arthritis, rheumatoid arthritis or ulcerative colitis)

- Patient has undergone a major surgery, including surgery for a new artificial implant
and/or device, within 6 weeks prior to the initiation of ADXS11-001 treatment; NOTE:
all toxicities and/or complications must have recovered to baseline or grade 1 prior
to the initiation of ADXS11-001 study therapy; sponsor must be consulted prior to
enrolling patients on the study who recently had a major surgery or have new
artificial implant, and/or devices

- Patient has a known allergy to any component of the study treatment formulations

- Patient has a history of listeriosis or prior ADXS11-001 therapy