Vaccine Therapy in Treating Patients With Persistent or Recurrent Cervical Cancer

• Number of patients with dose-limiting toxicities [ Designated as safety issue: Yes ]
• Frequency and severity of adverse effects as assessed by CTCAE v 4.0 [ Designated as safety issue: Yes ]
• Proportion of patients who survive for at least 12 months [ Designated as safety issue: No ]

• Distribution of overall survival [ Designated as safety issue: No ]
• Distribution of progression-free survival [ Designated as safety issue: No ]
• Proportion of patients who have objective tumor response (complete or partial) [ Designated as safety issue: No ]

RATIONALE: Vaccines may help the body build an effective immune response to kill tumor cells.

PURPOSE: This phase II clinical trial is studying the side effects and how well vaccine therapy works in treating patients with persistent or recurrent cervical cancer.

OBJECTIVES:

Primary

• To evaluate the tolerability, safety, and nature and degree of toxicity of ADX11-001 by the numbers of patients with dose-limiting toxicities (DLTs) and adverse events as assessed by the CTCAE v4.0.
• 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

• To characterize the distribution of progression-free survival and overall survival.
• To examine the proportion of patients with objective tumor response.

Tertiary

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

OUTLINE: This is a multicenter study.

Patients receive live-attenuated Listeria monocytogenes cancer vaccine ADXS11-001 IV over 15 minutes on day 1. Treatment repeats every 28 days for 3 courses in the absence of disease progression or unacceptable toxicity.

Tumor tissue and serum samples may be collected periodically for translational research.

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

• Biological: live-attenuated Listeria monocytogenes cancer vaccine ADXS11-001
• Other: laboratory biomarker analysis

DISEASE CHARACTERISTICS:

• Patients must have persistent or recurrent squamous cell 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 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 CT, 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 have had one prior systemic chemotherapeutic regimen for management of advanced, metastatic, or recurrent carcinoma of the cervix

  • Chemotherapy administered concurrently 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 must not be eligible for a higher priority 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

PATIENT CHARACTERISTICS:

• GOG performance status of 0, 1, or 2 (patients who have received one prior regimen) or GOG performance status of 0 or 1 (patients who have received two prior regimens)
• Platelet count greater than or equal to 100,000/mcL
• ANC count greater than or equal to 1,500/mcL
• Lymphocyte count greater than or equal to 700/mcL
• Creatinine less than or equal to 1.5 x institutional upper limit of normal (ULN)
• Bilirubin less than or equal to 1.5 x ULN
• AST and ALT less than or equal to 1.5 x ULN
• GGT less than or equal to 1.5 x ULN
• Alkaline phosphatase less than or equal to 2.5 x ULN
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use an effective form of contraception during protocol therapy and for at least two months following completion of protocol therapy
• Able to swallow pills
• Neuropathy (sensory and motor) less than or equal to grade 1
• Patients should be free of active infection requiring antibiotics
• Patients must have at least 5 mm dermal response to one of the test antigens

• No patients with uncontrolled intercurrent illness including, but not limited to:

  • Ongoing or active infection
  • Symptomatic congestive heart failure
  • Unstable angina pectoris
  • Cardiac arrhythmia
  • Psychiatric illness/social situations that would limit compliance with study requirements
• No patients with liver cirrhosis or any other impaired hepatic function as determined by serum enzymes
• No patients known to be seropositive for HIV and/or active hepatitis, even if liver function studies are in the eligible range
• No patients with a history of sickle cell trait/disease
• Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer or localized cancer of the breast, head and neck, or skin, are excluded if there is any evidence of other malignancy being present within the last three years
• No patients allergic to both penicillin and trimethoprim-sulfa (including history of rash or anaphylaxis)
• No patients allergic to naproxen

PRIOR CONCURRENT THERAPY:

• See Disease Characteristics
• No patients with a prior splenectomy
• Patients must have NOT received any non-cytotoxic chemotherapy for management of recurrent or persistent disease
• No patients who have received prior therapy with ADXS11-001
• Patients are excluded if their previous cancer treatment contraindicates this protocol therapy
• Any prior radiation therapy must be completed at least 4 weeks prior to registration

• 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 are allowed to receive, but are not required to receive, one additional cytotoxic regimen for management of recurrent or persistent disease
• 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)
• Recovered from effects of recent surgery, radiotherapy, or chemotherapy

• 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

• No patients who have received within the past four weeks, or who are currently receiving, steroids

  • Topical corticosteroids and occasional inhaled corticosteroids are allowed
• No patients currently receiving antibiotics

• National Cancer Institute (NCI)
• Advaxis, Inc.