Vaccine Therapy in Treating Patients With Persistent or Recurrent Cervical Cancer

• Sponsor: Gynecologic Oncology Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT01266460
• Collaborator: Advaxis, Inc. (Industry), National Cancer Institute (NCI) (NIH)
• Enrollment: 54
• Locations: 24
• Arm: 1
• Actual Duration (Months): 88.3
• Patients Per Site: 2.3
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Recurrent Cervical Carcinoma	Biological: Attenuated Live Listeria Encoding HPV 16 E7 Vaccine ADXS11-001; Other: Laboratory Biomarker Analysis	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. 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.

2. 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:

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

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

TERTIARY OBJECTIVES:

1. 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.

2. 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 54 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: May 23, 2011
• Actual Primary Completion Date: Oct 2, 2018
• Actual Study Completion Date: Oct 2, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (ADXS11-001) Patients receive live-attenuated Listeria monocytogenes cancer vaccine ADXS11-001 IV over 30 minutes on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.	Biological: Attenuated Live Listeria Encoding HPV 16 E7 Vaccine ADXS11-001; Given IV; Other Names: ADXS11-001 ADXS11-001 Vaccine Attenuated Live Listeria Encoding HPV 16 E7 Vaccine Attenuated Live Listeria Encoding Human Papilloma Virus 16 E7 Vaccine Lm-LLO-E7 Lovaxin-C ; Other: Laboratory Biomarker Analysis; Correlative studies

Outcome Measures

Primary Outcome Measures

1. Number of Patients With Dose-limiting Toxicities, as Assessed by CTCAE v 4.0 [28 days]

   Number of patients with dose-limiting toxicities, as assessed by CTCAE v 4.0

2. Incidence of Adverse Effects as Assessed by CTCAE v 4.0 [Adverse events were collected an average of 4 years 7 months]

   Incidence of adverse effects as assessed by CTCAE v 4.0 (i.e. the number of patients experiencing at least one grade 3 adverse event)

3. Number of Patients Who Survive for at Least 12 Months [12 months]

   The number of patients (and percentage) who survive for at least 12 months.

Secondary Outcome Measures

1. Distribution of Overall Survival [Patients will be followed (physical exams and histories) every three months for the first three years, then every six months for the next two years. Patients will be monitored for delayed toxicity and survival for 5-year period, unless consent withdrawn.]

   Characterized with Kaplan-Meier plots and estimates of the median time until death.

2. Distribution of Progression-free Survival [Patients will be followed (physical exams and histories) every three months for the first three years, then every six months for the next two years. Patients will be monitored for delayed toxicity and survival for 5-year period, unless consent withdrawn.]

   Characterized with Kaplan-Meier plots and estimates of the median time until progression. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.

3. Number of Patients Who Have Objective Tumor Response (Complete or Partial) [Patients will be followed (physical exams and histories) every three months for the first three years, then every six months for the next two years. Patients will be monitored for delayed toxicity and survival for 5-year period, unless consent withdrawn.]

   The number of patients who have objective tumor response (complete response or partial response). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Other Outcome Measures

1. Changes in Clinical Immunology Based Upon Serum [Baseline to up to 24 hours after dose 3]

   Examined with descriptive statistics and graphics, and their relationship with survival and tumor response will be examined with proportional hazards and logistic regression models, as appropriate.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama	United States	35233
2	Saint Joseph's Hospital and Medical Center	Phoenix	Arizona	United States	85013
3	UC San Diego Moores Cancer Center	La Jolla	California	United States	92093
4	Los Angeles County-USC Medical Center	Los Angeles	California	United States	90033
5	USC / Norris Comprehensive Cancer Center	Los Angeles	California	United States	90033
6	UCSF Medical Center-Mount Zion	San Francisco	California	United States	94115
7	UCSF Medical Center-Mission Bay	San Francisco	California	United States	94158
8	Memorial Health University Medical Center	Savannah	Georgia	United States	31404
9	University of Kansas Cancer Center	Kansas City	Kansas	United States	66160
10	Sinai Hospital of Baltimore	Baltimore	Maryland	United States	21215
11	Johns Hopkins University/Sidney Kimmel Cancer Center	Baltimore	Maryland	United States	21287
12	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109
13	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
14	Montefiore Medical Center-Einstein Campus	Bronx	New York	United States	10461
15	Carolinas Medical Center/Levine Cancer Institute	Charlotte	North Carolina	United States	28203
16	Case Western Reserve University	Cleveland	Ohio	United States	44106
17	Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210
18	UH Seidman Cancer Center at Lake Health Mentor Campus	Mentor	Ohio	United States	44060
19	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104
20	Oklahoma Cancer Specialists and Research Institute-Tulsa	Tulsa	Oklahoma	United States	74146
21	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas	United States	75390
22	University of Texas Medical Branch	Galveston	Texas	United States	77555-0565
23	Virginia Commonwealth University/Massey Cancer Center	Richmond	Virginia	United States	23298
24	Froedtert and the Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53226

Sponsors and Collaborators

• Gynecologic Oncology Group
• Advaxis, Inc.
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Warner K Huh, NRG Oncology

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 18, 2016

More Information

Publications

None provided.

• Responsible Party: Gynecologic Oncology Group
• ClinicalTrials.gov Identifier: NCT01266460
• Other Study ID Numbers: GOG-0265; NCI-2011-02671; GOG-0265; CDR0000691288; GOG-0265; GOG-0265; U10CA180830; U10CA180868; U10CA027469
• First Posted: Dec 24, 2010
• Last Update Posted: Sep 11, 2020
• Last Verified: Aug 1, 2020

• Additional relevant MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Carcinoma, Adenosquamous; Recurrence; Vaccines

Study Results

Participant Flow

Recruitment Details	GOG-0265 enrolled 54 patients from May 23, 2011 to September of 2015. Of the 54 patients enrolled, 50 patients received treatment.

Arm/Group Title	Treatment (ADXS11-001)
Arm/Group Description	Patients receive live-attenuated Listeria monocytogenes cancer vaccine ADXS11-001 IV over 30 minutes on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Attenuated Live Listeria Encoding HPV 16 E7 Vaccine ADXS11-001: Given IV Laboratory Biomarker Analysis: Correlative studies
Period Title: Overall Study
STARTED	50
COMPLETED	16
NOT COMPLETED	34

Baseline Characteristics

Arm/Group Title	Treatment (ADXS11-001)
Arm/Group Description	Patients receive live-attenuated Listeria monocytogenes cancer vaccine ADXS11-001 IV over 30 minutes on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Attenuated Live Listeria Encoding HPV 16 E7 Vaccine ADXS11-001: Given IV Laboratory Biomarker Analysis: Correlative studies
Overall Participants	50
Age, Customized (Count of Participants)
20 - 29 years	25 50%
30 - 39 years	11 22%
40 - 49 years	17 34%
50 - 59 years	9 18%
60 - 69 years	10 20%
70 - 79 years	1 2%
>= 80 years	0 0%
Sex: Female, Male (Count of Participants)
Female	50 100%
Male	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 6%
Not Hispanic or Latino	45 90%
Unknown or Not Reported	2 4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 2%
Asian	4 8%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	5 10%
White	37 74%
More than one race	1 2%
Unknown or Not Reported	2 4%

Outcome Measures

1. Primary Outcome

Title	Number of Patients With Dose-limiting Toxicities, as Assessed by CTCAE v 4.0
Description	Number of patients with dose-limiting toxicities, as assessed by CTCAE v 4.0
Time Frame	28 days

Outcome Measure Data

Analysis Population Description

Only the first six patients were analyzed for Dose Limiting Toxicities.

Arm/Group Title	Treatment (ADXS11-001)
Arm/Group Description	Patients receive live-attenuated Listeria monocytogenes cancer vaccine ADXS11-001 IV over 30 minutes on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Attenuated Live Listeria Encoding HPV 16 E7 Vaccine ADXS11-001: Given IV Laboratory Biomarker Analysis: Correlative studies
Measure Participants	6
Count of Participants [Participants]	0 0%

2. Primary Outcome

Title	Incidence of Adverse Effects as Assessed by CTCAE v 4.0
Description	Incidence of adverse effects as assessed by CTCAE v 4.0 (i.e. the number of patients experiencing at least one grade 3 adverse event)
Time Frame	Adverse events were collected an average of 4 years 7 months

Outcome Measure Data

Analysis Population Description

Eligible and evaluable.

Arm/Group Title	Treatment (ADXS11-001)
Arm/Group Description	Patients receive live-attenuated Listeria monocytogenes cancer vaccine ADXS11-001 IV over 30 minutes on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Attenuated Live Listeria Encoding HPV 16 E7 Vaccine ADXS11-001: Given IV Laboratory Biomarker Analysis: Correlative studies
Measure Participants	50
Count of Participants [Participants]	29 58%

3. Primary Outcome

Title	Number of Patients Who Survive for at Least 12 Months
Description	The number of patients (and percentage) who survive for at least 12 months.
Time Frame	12 months

Outcome Measure Data

Analysis Population Description

Eligible and evaluable

Arm/Group Title	Treatment (ADXS11-001)
Arm/Group Description	Patients receive live-attenuated Listeria monocytogenes cancer vaccine ADXS11-001 IV over 30 minutes on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Attenuated Live Listeria Encoding HPV 16 E7 Vaccine ADXS11-001: Given IV Laboratory Biomarker Analysis: Correlative studies
Measure Participants	50
Count of Participants [Participants]	19 38%

4. Secondary Outcome

Title	Distribution of Overall Survival
Description	Characterized with Kaplan-Meier plots and estimates of the median time until death.
Time Frame	Patients will be followed (physical exams and histories) every three months for the first three years, then every six months for the next two years. Patients will be monitored for delayed toxicity and survival for 5-year period, unless consent withdrawn.

Outcome Measure Data

Analysis Population Description

Eligible and evaluable.

Arm/Group Title	Treatment (ADXS11-001)
Arm/Group Description	Patients receive live-attenuated Listeria monocytogenes cancer vaccine ADXS11-001 IV over 30 minutes on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Attenuated Live Listeria Encoding HPV 16 E7 Vaccine ADXS11-001: Given IV Laboratory Biomarker Analysis: Correlative studies
Measure Participants	50
Median (95% Confidence Interval) [Months]	6.1

5. Secondary Outcome

Title	Distribution of Progression-free Survival
Description	Characterized with Kaplan-Meier plots and estimates of the median time until progression. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Time Frame	Patients will be followed (physical exams and histories) every three months for the first three years, then every six months for the next two years. Patients will be monitored for delayed toxicity and survival for 5-year period, unless consent withdrawn.

Outcome Measure Data

Analysis Population Description

Eligible and evaluable

Arm/Group Title	Treatment (ADXS11-001)
Arm/Group Description	Patients receive live-attenuated Listeria monocytogenes cancer vaccine ADXS11-001 IV over 30 minutes on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Attenuated Live Listeria Encoding HPV 16 E7 Vaccine ADXS11-001: Given IV Laboratory Biomarker Analysis: Correlative studies
Measure Participants	50
Median (95% Confidence Interval) [Months]	2.8

6. Secondary Outcome

Title	Number of Patients Who Have Objective Tumor Response (Complete or Partial)
Description	The number of patients who have objective tumor response (complete response or partial response). Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time Frame	Patients will be followed (physical exams and histories) every three months for the first three years, then every six months for the next two years. Patients will be monitored for delayed toxicity and survival for 5-year period, unless consent withdrawn.

Outcome Measure Data

Analysis Population Description

Eligible and evaluable.

Arm/Group Title	Treatment (ADXS11-001)
Arm/Group Description	Patients receive live-attenuated Listeria monocytogenes cancer vaccine ADXS11-001 IV over 30 minutes on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Attenuated Live Listeria Encoding HPV 16 E7 Vaccine ADXS11-001: Given IV Laboratory Biomarker Analysis: Correlative studies
Measure Participants	50
Complete Response	0 0%
Partial Response	2 4%
Stable Disease	5 10%
Progressive Disease	32 64%
Not Evaluable	11 22%

7. Other Pre-specified Outcome

Title	Changes in Clinical Immunology Based Upon Serum
Description	Examined with descriptive statistics and graphics, and their relationship with survival and tumor response will be examined with proportional hazards and logistic regression models, as appropriate.
Time Frame	Baseline to up to 24 hours after dose 3

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	For each patient, adverse events are collected from study entry until the end of follow up, an average of 4 years 7 months.
Arm/Group Title	Treatment (ADXS11-001)
Arm/Group Description	Patients receive live-attenuated Listeria monocytogenes cancer vaccine ADXS11-001 IV over 30 minutes on day 1. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Attenuated Live Listeria Encoding HPV 16 E7 Vaccine ADXS11-001: Given IV Laboratory Biomarker Analysis: Correlative studies
All Cause Mortality
	Treatment (ADXS11-001)
	Affected / at Risk (%)	# Events
Total	43/50 (86%)
Serious Adverse Events
	Treatment (ADXS11-001)
	Affected / at Risk (%)	# Events
Total	27/50 (54%)
Cardiac disorders
Sinus tachycardia	1/50 (2%)
Gastrointestinal disorders
Abdominal pain	1/50 (2%)
Ascites	1/50 (2%)
Constipation	2/50 (4%)
Rectal hemorrhage	1/50 (2%)
Vomiting	3/50 (6%)
General disorders
Chills	3/50 (6%)
Fatigue	1/50 (2%)
Fever	3/50 (6%)
General disorders and administration site conditions - Other, specify	1/50 (2%)
Malaise	1/50 (2%)
Pain	2/50 (4%)
Hepatobiliary disorders
Hepatic failure	1/50 (2%)
Immune system disorders
Cytokine release syndrome	6/50 (12%)
Infections and infestations
Infections and infestations - Other, specify	1/50 (2%)
Lung infection	1/50 (2%)
Sepsis	1/50 (2%)
Urinary tract infection	2/50 (4%)
Injury, poisoning and procedural complications
Fracture	1/50 (2%)
Investigations
Alkaline phosphatase increased	1/50 (2%)
Blood bilirubin increased	1/50 (2%)
Creatinine increased	4/50 (8%)
GGT increased	1/50 (2%)
INR increased	1/50 (2%)
Urine output decreased	1/50 (2%)
Metabolism and nutrition disorders
Dehydration	1/50 (2%)
Hypercalcemia	1/50 (2%)
Hyperglycemia	2/50 (4%)
Hyperkalemia	1/50 (2%)
Hypoalbuminemia	1/50 (2%)
Hypocalcemia	1/50 (2%)
Hyponatremia	1/50 (2%)
Musculoskeletal and connective tissue disorders
Back pain	2/50 (4%)
Pain in extremity	2/50 (4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	1/50 (2%)
Nervous system disorders
Lethargy	1/50 (2%)
Psychiatric disorders
Confusion	1/50 (2%)
Delirium	1/50 (2%)
Renal and urinary disorders
Acute kidney injury	3/50 (6%)
Chronic kidney disease	1/50 (2%)
Renal and urinary disorders - Other, specify	1/50 (2%)
Urinary tract obstruction	3/50 (6%)
Reproductive system and breast disorders
Vaginal fistula	1/50 (2%)
Vaginal hemorrhage	1/50 (2%)
Vaginal pain	1/50 (2%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/50 (2%)
Hypoxia	1/50 (2%)
Pleural effusion	2/50 (4%)
Vascular disorders
Flushing	1/50 (2%)
Hypotension	6/50 (12%)
Thromboembolic event	2/50 (4%)
Other (Not Including Serious) Adverse Events
	Treatment (ADXS11-001)
	Affected / at Risk (%)	# Events
Total	50/50 (100%)
Blood and lymphatic system disorders
Lymph node pain	1/50 (2%)
Cardiac disorders
Chest pain - cardiac	1/50 (2%)
Sinus tachycardia	11/50 (22%)
Ventricular tachycardia	1/50 (2%)
Ear and labyrinth disorders
Tinnitus	2/50 (4%)
Eye disorders
Blurred vision	1/50 (2%)
Eye disorders - Other, specify	1/50 (2%)
Photophobia	1/50 (2%)
Gastrointestinal disorders
Abdominal distension	2/50 (4%)
Abdominal pain	14/50 (28%)
Anal pain	1/50 (2%)
Ascites	2/50 (4%)
Bloating	2/50 (4%)
Constipation	18/50 (36%)
Diarrhea	3/50 (6%)
Dry mouth	1/50 (2%)
Duodenal stenosis	1/50 (2%)
Dysphagia	2/50 (4%)
Gastroesophageal reflux disease	3/50 (6%)
Hemorrhoidal hemorrhage	1/50 (2%)
Hemorrhoids	1/50 (2%)
Mucositis oral	1/50 (2%)
Nausea	20/50 (40%)
Vomiting	15/50 (30%)
General disorders
Chills	29/50 (58%)
Edema limbs	13/50 (26%)
Edema trunk	1/50 (2%)
Fatigue	37/50 (74%)
Fever	20/50 (40%)
Flu like symptoms	8/50 (16%)
General disorders and administration site conditions - Other, specify	1/50 (2%)
Infusion related reaction	1/50 (2%)
Localized edema	1/50 (2%)
Malaise	4/50 (8%)
Non-cardiac chest pain	2/50 (4%)
Pain	9/50 (18%)
Hepatobiliary disorders
Cholecystitis	1/50 (2%)
Gallbladder pain	1/50 (2%)
Hepatobiliary disorders - Other, specify	1/50 (2%)
Immune system disorders
Cytokine release syndrome	8/50 (16%)
Infections and infestations
Infections and infestations - Other, specify	1/50 (2%)
Peripheral nerve infection	1/50 (2%)
Rhinitis infective	1/50 (2%)
Urinary tract infection	5/50 (10%)
Vaginal infection	1/50 (2%)
Injury, poisoning and procedural complications
Fracture	1/50 (2%)
Investigations
Alanine aminotransferase increased	11/50 (22%)
Alkaline phosphatase increased	12/50 (24%)
Aspartate aminotransferase increased	13/50 (26%)
Cardiac troponin I increased	1/50 (2%)
Cholesterol high	1/50 (2%)
Creatinine increased	5/50 (10%)
GGT increased	14/50 (28%)
INR increased	1/50 (2%)
Lymphocyte count decreased	5/50 (10%)
Weight loss	4/50 (8%)
Metabolism and nutrition disorders
Anorexia	13/50 (26%)
Hypercalcemia	5/50 (10%)
Hyperglycemia	10/50 (20%)
Hyperkalemia	2/50 (4%)
Hypertriglyceridemia	1/50 (2%)
Hypoalbuminemia	11/50 (22%)
Hypocalcemia	7/50 (14%)
Hypoglycemia	2/50 (4%)
Hypokalemia	7/50 (14%)
Hypomagnesemia	10/50 (20%)
Hyponatremia	8/50 (16%)
Hypophosphatemia	4/50 (8%)
Metabolism and nutrition disorders - Other, specify	1/50 (2%)
Musculoskeletal and connective tissue disorders
Arthralgia	4/50 (8%)
Back pain	17/50 (34%)
Bone pain	1/50 (2%)
Buttock pain	1/50 (2%)
Flank pain	2/50 (4%)
Generalized muscle weakness	5/50 (10%)
Muscle weakness lower limb	1/50 (2%)
Musculoskeletal and connective tissue disorder - Other, specify	1/50 (2%)
Myalgia	12/50 (24%)
Pain in extremity	5/50 (10%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumor pain	1/50 (2%)
Nervous system disorders
Dizziness	7/50 (14%)
Headache	18/50 (36%)
Memory impairment	2/50 (4%)
Nervous system disorders - Other, specify	1/50 (2%)
Paresthesia	1/50 (2%)
Peripheral motor neuropathy	1/50 (2%)
Peripheral sensory neuropathy	7/50 (14%)
Somnolence	1/50 (2%)
Psychiatric disorders
Anxiety	7/50 (14%)
Depression	8/50 (16%)
Insomnia	8/50 (16%)
Renal and urinary disorders
Acute kidney injury	4/50 (8%)
Bladder perforation	1/50 (2%)
Bladder spasm	1/50 (2%)
Cystitis noninfective	1/50 (2%)
Hematuria	4/50 (8%)
Urinary frequency	5/50 (10%)
Urinary incontinence	1/50 (2%)
Urinary retention	1/50 (2%)
Urinary tract obstruction	1/50 (2%)
Urinary tract pain	3/50 (6%)
Urinary urgency	1/50 (2%)
Reproductive system and breast disorders
Menorrhagia	1/50 (2%)
Pelvic pain	5/50 (10%)
Vaginal discharge	2/50 (4%)
Vaginal fistula	1/50 (2%)
Vaginal hemorrhage	3/50 (6%)
Vaginal pain	2/50 (4%)
Respiratory, thoracic and mediastinal disorders
Cough	6/50 (12%)
Dyspnea	12/50 (24%)
Hiccups	1/50 (2%)
Hoarseness	1/50 (2%)
Hypoxia	1/50 (2%)
Nasal congestion	3/50 (6%)
Pleural effusion	1/50 (2%)
Productive cough	1/50 (2%)
Respiratory, thoracic and mediastinal disorders - Other, specify	1/50 (2%)
Sore throat	3/50 (6%)
Skin and subcutaneous tissue disorders
Alopecia	2/50 (4%)
Dry skin	1/50 (2%)
Hyperhidrosis	2/50 (4%)
Pruritus	1/50 (2%)
Rash maculo-papular	2/50 (4%)
Skin and subcutaneous tissue disorders - Other, specify	2/50 (4%)
Skin ulceration	1/50 (2%)
Vascular disorders
Flushing	1/50 (2%)
Hot flashes	4/50 (8%)
Hypertension	4/50 (8%)
Hypotension	16/50 (32%)
Lymphedema	3/50 (6%)
Thromboembolic event	1/50 (2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.