GOG 265: A Phase II Evaluation of ADXS11-001 (NSC 752718, BB-IND #13,712) in the Treatment of Persistent or Recurrent Squamous or Non-Squamous Cell Carcinoma of the Cervix

Summary

This is a single-arm, multicenter, two-stage Phase ii study, and no randomization is involved. The study also includes a safety lead-in, in which the dose limiting toxicities of the study agent will be assessed in the first 6 patients enrolled.

Treatment Plan:
aDXS11-001 will be given at a dose of 1x109 cfu intravenously once every 28 days for 3 total doses. The drug will be given as an 80ml infusion over 15 minutes and will be given on Day 1 of each cycle. at 72 hours following each dose a 7 day regimen of oral ampicillin will be administered (on Days 4 to 10).

The study includes a safety lead-in, in which the dose limiting toxicities of the study agent will be assessed in the first 6 patients enrolled. Further accrual will be held until all 6 patients have completed 28 day observation after cycle 1 treatment.

Screening:
* History and physical examination which may include a pelvic examination.
* Vital signs will be checked (includes blood pressure, temperature, pulse and respiratory rate monitoring)
* Blood tests (1 tablespoon) to measure blood counts, blood mineral levels, and check liver and kidney function
* a blood pregnancy test (1 teaspoon) if she is capable of becoming pregnant
* Chest imaging to measure detectable tumor (X-ray or CT scan of the chest)
* CT scan or MRi of the abdomen and pelvis to measure detectable tumor
* Review of medications and supplements she is currently taking

Drug interactions with aDXS11-001: While she is on this study she should not take any immunosuppressive steroids, such as prednisone and prednisolone. The doctor will review all of the medications and supplements she is currently taking before starting her on this drug. She may need to change one or more of her regular medications under the direction of her doctor if it is safe to do so in order to participate in this study. She should not take any new medications or dietary supplements without discussing it with her study doctor first.

During the study
if the exams, tests and procedures show that she can be in the study, and she chooses to take part, then she will need the following tests and procedures. They are part of regular cancer care.

* if she is one of the first six patients enrolled on this study she will return on Days 1-4 to have a history a physical examination and her vital signs checked. For all other patients they will be seen on Days 1, 2 and 4 of each cycle.
* Vital signs and a physical will be done weekly, sometimes more frequently (this will include monitoring of blood pressure, temperature, pulse and respiratory rate)
* Blood tests to measure blood counts, blood mineral levels, and check liver and kidney function will be done weekly or more often if needed
* urinalysis will be done prior to each treatment.

The patient will undergo the following procedures that are not part of regular cancer care and are being done only because she is in this study.
* Complete a patient pill calendar

in addition, she will be asked to provide samples of her tumor tissue (if available from a previous biopsy or surgery) and some of her blood for laboratory testing that is not part of regular cancer care and is only being done because she is in this study.

She can still participate in this study if she does not give permission for her tumor tissue and/or blood to be collected and used for this optional research. For more information on this optional research, please see the last three sections of optional Consent Form. one section provides general information about the collection and use of specimens for research. another section describes specific information about the use of specimens for this research study. The last section focuses on issues regarding future research.

Participant Eligibility

3.11 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.
3.12 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.
3.13 Patient must have at least one
* target lesion
* to be used to assess response on this protocol as defined by RECIST 1.1 (Section 8.1). 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.
3.14 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.
3.15 Patients who have received one prior regimen must have a GOG performance Status of 0, 1, or 2. Patients who have received two prior regimens must have a GOG Performance Status of 0 or 1.
3.16 Recovery from effects of recent surgery, radiotherapy, or chemotherapy
3.161 Patients should be free of active infection requiring antibiotics.
3.162 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.
3.163 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.
3.164 Any prior radiation therapy must be completed at least 4 weeks prior to registration. (02/06/2012)
3.17 Prior therapy
3.171 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). (02/06/2012)
3.172 Patients are allowed to receive, but are not required to receive, one additional cytotoxic regimen for management of recurrent or persistent disease. (02/06/2012)
3.173 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). (02/06/2012)
3.18 Patients must have adequate:
3.181 Bone marrow function: Platelet count greater than or equal to 100,000/mcl and ANC count greater than or equal to 1,500/mcl. Lymphocyte count greater than or equal to 700/mcl.
3.182 Renal function: creatinine less than or equal to 1.5 x institutional upper limit normal (ULN).
3.183 Hepatic function: Bilirubin, AST, ALT, and GGT less than or equal to 1.5 x ULN and alkaline phosphatase less than or equal to 2.5 x ULN. (02/06/2012)
3.184 Neurologic function: Neuropathy (sensory and motor) less than or equal to Grade 1.
3.19 Patients must have signed an approved informed consent and authorization permitting release of personal health information.
3.110 Patients must meet pre-entry requirements as specified in Section 7.0.
3.111 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. (5/23/2011)
3.112 Patients cannot be lactating.
3.113 Patients must be > 18 years old.
3.114 Patients must be able to swallow pills.