Vaccine Therapy in Treating Patients With Persistent or Recurrent Cervical Cancer
Condition: Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Recurrent Cervical Carcinoma
MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Carcinoma, Adenosquamous; Recurrence
Intervention: Attenuated Live Listeria Encoding HPV 16 E7 Vaccine ADXS11-001; Laboratory Biomarker Analysis
Intervention description: Given IV; Correlative studies
Intervention MeSH terms: Vaccines
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 54.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies the side effects and how well vaccine therapy works in treating
      patients with cervical cancer that does not go to remission despite treatment (persistent) or
      has come back (recurrent). Vaccines therapy may help the body build an effective immune
      response to kill tumor cells.
    

Eligibility criteria:

        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