High Risk Cervical Cancer, Advanced Cervical Cancer
Conditions
Brief summary
Locally advanced cervical cancer at higher risk for recurrence (HRLACC) following concurrent chemotherapy and radiation therapy. This is a group of participants with a significant unmet need. The estimated probability of disease recurrence or death within 4 years of diagnosis is 50% and the prognosis is very grave for those who experience a recurrence. The purpose of the study was to compare the disease free survival (DFS) of ADXS11-001 to placebo administered following cisplatin-based combination chemotherapy and radiation (CCRT) with curative intent in participants with HRLACC.
Detailed description
This was a double-blind, placebo-controlled randomized study of ADXS11-001 administered in the adjuvant setting after completion of CCRT in participants with HRLACC, or death. All eligible participants had received CCRT administered with curative intent according to institutional/national guidelines as well as meeting the minimum standards defined in the protocol. Participants initiated the Screening period within 10 weeks after the completion of CCRT. Baseline radiographic assessments and clinical laboratory assessments were completed no longer than 28 days prior to and 3 days prior to the first study treatment infusion, respectively. Eligible participants were randomized 1:2 to receive either placebo or ADXS11-001. Participants received 1 infusion of study treatment administered every 3 weeks for 3 doses for the first 3 months. Thereafter, participants received study treatment every 8 weeks for a total of 5 doses or until disease recurrence. Participants received a 7-day course of an oral antibiotic or placebo starting 72 hours following the completion of study treatment administration.
Interventions
DRUGADXS11-001
DRUGPlacebo
Sponsors
Gynecologic Oncology Group
Advaxis, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants must have a biopsy confirmed diagnosis of squamous cell, adenocarcinoma, or adenosquamous carcinoma of the cervix. Histologic confirmation of the original primary tumor is required. * Participants with HRLACC. * Participants included those with stage IB2, IIA2, IIB with pelvic lymph node metastases; all FIGO Stage IIIA, IIIB, IVA or any FIGO Stage (except stage IVB) with para-aortic lymph node metastases as defined by the FIGO 2014 staging criteria for carcinoma of the cervix uteri. * Participants must have received definitive therapy with curative intent, which consist of at least 4 weeks of treatment with cisplatin and a minimum of 40Gy external beam radiation therapy (EBRT). * Have performance status of 0 or 1 on the gynaecologic Oncology Group (GOG) performance scale * Demonstrate adequate organ function
Exclusion criteria
* Has not achieved disease-free status after completion of CCRT administered with curative intent. * Has International Federation of Gynecology and Obstetrics (FIGO) Stage IVB * Has histologies other than squamous cell, adenocarcinoma, or adenosquamous carcinoma of the cervix. * 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)). * Has a contraindication (sensitivity or allergy) to trimethoprim/sulfamethoxazole and ampicillin. * Has undergone a previous hysterectomy defined as removal of the entire uterus or will have a hysterectomy as part of their initial cervical cancer therapy. NOTE: Women who have had a partial/subtotal hysterectomy are eligible to participate in the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease Free Survival (DFS) | From the time of randomization to recurrence or death (Maximum duration: 44.7 months) | DFS was defined as the time from randomization until death or recurrence. The date of recurrence was defined as the date of the first time point when recurrence of disease was determined. The determination of recurrence should occur by definitive pathologic tissue confirmation (e.g., biopsy/fine needle aspirate). However, in those cases where it was not medically feasible to obtain a tissue sample then radiographic evidence, when confirmed by independent radiology review, was used to determine recurrence. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events | From first dose of study drug until end of study (Up to 44.7 months) | Adverse event (AE): any untoward medical occurrence in a participant administered a study treatment & which did not necessarily have to have a causal relationship with the study treatment. An AE is, any unfavorable & unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of study treatment. AE with onset dates on or after the first dose of study treatment were considered treatment emergent. |
| Overall Survival (OS) | From the date of randomization until death due to any cause (Maximum duration: 44.7 months) | Overall survival was defined as the time from the date of randomization until death due to any cause. |
Countries
Argentina, Brazil, Canada, Chile, Malaysia, Mexico, Poland, Russia, Serbia, South Korea, Spain, Taiwan, Ukraine, United States
Participant flow
Recruitment details
Participants with high-risk disease as determined by prognostic factors such as tumor staging, nodal involvement, extent of nodal involvement, and location of nodal involvement were enrolled in this study.
Pre-assignment details
Participants completed cisplatin-based combination chemotherapy and radiation (CCRT) before enrollment into the study.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Participants with HRLACC received ADXS11-001 matching placebo by intravenous infusion for approximately 60 minutes every 3 weeks for 3 doses (Weeks 1, 4 and 7) and thereafter, every 8 weeks for 5 doses (Weeks 15, 23, 31, 39, and 47) during treatment phase or until disease recurrence. Participants received a 7-day course placebo matching to either trimethoprim/sulfamethoxazole or ampicillin starting 72 hours post treatment in prime and maintenance phase. | 37 |
| ADXS11-001 Participants with HRLACC received ADXS11-001 at a dose of 1x10\^9 CFU by intravenous infusion for approximately 60 minutes every 3 weeks for 3 doses (Weeks 1, 4 and 7) and thereafter, every 8 weeks for 5 doses (Weeks 15, 23, 31, 39, and 47) during treatment phase or until disease recurrence. Participants received a 7-day course of either trimethoprim/sulfamethoxazole or ampicillin starting 72 hours post treatment in prime and maintenance phase. | 72 |
| Total | 109 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 1 | 5 |
| Overall Study | Lost to Follow-up | 4 | 8 |
| Overall Study | Miscellaneous | 11 | 2 |
| Overall Study | Progressive Disease | 0 | 2 |
| Overall Study | Withdrawal by Subject | 12 | 35 |
Baseline characteristics
| Characteristic | ADXS11-001 | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 49.3 years STANDARD_DEVIATION 10.61 | 48.2 years STANDARD_DEVIATION 10.59 | 46.0 years STANDARD_DEVIATION 10.34 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 15 Participants | 23 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 57 Participants | 85 Participants | 28 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 9 Participants | 11 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 5 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 7 Participants | 9 Participants | 2 Participants |
| Race (NIH/OMB) White | 53 Participants | 83 Participants | 30 Participants |
| Sex: Female, Male Female | 72 Participants | 109 Participants | 37 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 37 | 5 / 72 |
| other Total, other adverse events | 30 / 37 | 62 / 72 |
| serious Total, serious adverse events | 3 / 37 | 10 / 72 |
Outcome results
Primary
Disease Free Survival (DFS)
DFS was defined as the time from randomization until death or recurrence. The date of recurrence was defined as the date of the first time point when recurrence of disease was determined. The determination of recurrence should occur by definitive pathologic tissue confirmation (e.g., biopsy/fine needle aspirate). However, in those cases where it was not medically feasible to obtain a tissue sample then radiographic evidence, when confirmed by independent radiology review, was used to determine recurrence.
Time frame: From the time of randomization to recurrence or death (Maximum duration: 44.7 months)
Population: This endpoint was not reported as the study was terminated early due to business reasons, therefore, no efficacy data was collected.
Secondary
Number of Participants With Treatment Emergent Adverse Events
Adverse event (AE): any untoward medical occurrence in a participant administered a study treatment & which did not necessarily have to have a causal relationship with the study treatment. An AE is, any unfavorable & unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening of a pre-existing condition that was temporally associated with the use of study treatment. AE with onset dates on or after the first dose of study treatment were considered treatment emergent.
Time frame: From first dose of study drug until end of study (Up to 44.7 months)
Population: AT Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Treatment Emergent Adverse Events | 30 Participants |
| ADXS11-001 | Number of Participants With Treatment Emergent Adverse Events | 62 Participants |
Secondary
Overall Survival (OS)
Overall survival was defined as the time from the date of randomization until death due to any cause.
Time frame: From the date of randomization until death due to any cause (Maximum duration: 44.7 months)
Population: This endpoint was not reported as the study was terminated early due to business reasons, therefore, no efficacy data was collected.