Vaccine Therapy in Treating Patients With Persistent or Recurrent Cervical Cancer

Study ID
GOG-0265

Cancer Related
Yes

Healthy Volunteers
No

Study Sites

  • Clements University Hospital
  • UT Southwestern Ambulatory Services
  • Zale Lipshy University Hospital

Contact
Annette Paulsen
214/648-2290
annette.paulsen@utsouthwestern.edu

Principal Investigator
David Miller

Official Title

A Phase II Evaluation of ADXS11-001 (NSC 752718) in the Treatment of Persistent or Recurrent Squamous or Non-squamous Cell Carcinoma of the Cervix

Brief Overview


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.

Summary


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.

Participant Eligibility


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 100,000/mcL

- Absolute neutrophil count (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

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or
equal to 1.5 x ULN

- Gamma-glutamyl transpeptidase (GGT) less than or equal to 1.5 x ULN

- Alkaline phosphatase less than or equal to 2.5 x ULN

- 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 be practicing an effective form of contraception during protocol
therapy and for at least two months following completion of protocol therapy

- 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 allergic to both penicillin and trimethoprim/sulfamethoxazole (including
history of rash or anaphylaxis)

- Patients allergic to naproxen

- Patients currently receiving antibiotics

- Patients who have received within the past four weeks, or who are currently
receiving, corticosteroids

- Topical corticosteroids and occasional inhaled corticosteroids are allowed

- 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