Primary objective:- Disease free survival (DFS)Secondary objective:- Safety & tolerability- Overall survival (OS)Exploratory objective:- Association between HPV subtypes and efficacy- Patient reported outcomes (PRO)Please refer to section 1 in…
ID
Source
Brief title
Condition
- Reproductive neoplasms female malignant and unspecified
- Cervix disorders (excl infections and inflammations)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint for this study is DFS measured from the time of
randomization to recurrence or death.
Secondary outcome
- The safety objective of this study is to determine and compare the frequency
and severity of AEs as assessed by NCI CTCAE v 4.03 for the regimens
administered on this study.
- The exploratory endpoint are patient reported outcomes
Background summary
As noted in the protocol section2.1, subjects with nodal disease, either pelvic
or para-aortic, and subjects with FIGO stage III and IV represent a subset of
subjects with LACC who are at greatest risk for recurrence and death from the
disease, and represent the population of LACC with the highest unmet need.
Therefore, by restricting the study population to high risk disease, as
determined by conventional and accepted diagnostic standards, we are focusing
our evaluation of ADXS11-001 on those subjects who would have the highest
potential to benefit and where the benefit/ risk ratio is acceptable for
treatment with experimental therapies.
Hypothesis: ADXS11-001 administered in the adjuvant setting, following
definitive therapy with CCRT, will significantly improve DFS rate as compared
with placebo.
Study objective
Primary objective:
- Disease free survival (DFS)
Secondary objective:
- Safety & tolerability
- Overall survival (OS)
Exploratory objective:
- Association between HPV subtypes and efficacy
- Patient reported outcomes (PRO)
Please refer to section 1 in the protocol page 12-13
Study design
This is a double-blind, placebo-controlled randomized study of ADXS11-001
administered in the adjuvant setting after completion of cisplatin-based CCRT
in subjects with locally advanced cervical cancer at higher risk for recurrence
(HRLACC), or death. The study will enroll subjects with high-risk disease as
determined by prognostic factors such as tumor staging, nodal involvement,
extent of nodal involvement, and location of nodal involvement. All eligible
subjects will have received CCRT administered with curative intent according to
institutional/national guidelines as well as meeting the minimum standards
defined in the protocol. Subjects must initiate the Screening period within 10
weeks after the completion of CCRT. Baseline radiographic assessments and
clinical laboratory assessments must be completed no longer than 28 days prior
to and 3 days prior to the first study treatment infusion, respectively.
Eligible subjects will be randomized 1:2 to receive either placebo or
ADXS11-001 (1 x 109 CFU infused over approximately 60 minutes). Subjects will
receive 1 infusion of study treatment (placebo or ADXS11-001, 1 x 109
CFU) administered every 3 weeks for 3 doses (Weeks 1, 4 and 7) for the first 3
months. This is called the Prime Phase at the study. Thereafter, subjects will
receive study treatment every 8 weeks (Weeks 15, 23, 31, 39, and 47) for a
total of 5 doses or until disease recurrence. This is called the Maintenance
Phase. Subjects will receive a 7-day course of an oral antibiotic (e.g.
trimethoprim/sulfamethoxazole (Bactrim) or Ampicillin; Bactrim is drug of
choice but Ampicillin may be used in specific cases (e.g. sulfa allergy) or
placebo starting 72 hours following the completion of
study treatment administration during the Prime and Maintenance phases. The
total treatment period will be approximately 1 year.
Lm Surveillance Period
Subjects will enter a 3-year Lm surveillance period beginning at the completion
of study treatment or at the time of study discontinuation. This period is
intended to help ensure the eradication of Lm bacteria in the body. It consists
of a 6-month course of trimethoprim/sulfamethoxazole, ampicillin or placebo and
a 2.5 year follow-up which will involve blood testing. The initiation of
antibiotic therapy will begin either 72 hours following the completion of the
last dose of study treatment or immediately following study discontinuation.
Follow-up and Post-Disease Recurrence Period
Subjects will continue to participate in the study and be followed for disease
recurrence after the completion of the study treatment period. In addition,
information regarding anticancer treatment(s) and interventions as well as
survival following confirmed disease recurrence will also be collected. This
period will last for a total of 5 years or death, whichever occurs earlier.
Intervention
ADXS11-001 (1 x 10 9) CFU or placebo IV infusion over 60 minutes.
1 dose administered every 3 weeks (Weeks 1, 4 and 7) for 3 doses (Prime Phase),
thereafter, subjects will receive 1 dose every 8 weeks (Weeks 15, 23, 31, 39,
and 47) (Maintenance Phase)
AND
80 mg Trimethoprim/ 400 sulfamethoxazole (or 500 mg ampicillin) or placebo
administered once daily for 7 consecutive days or ampicillin administered four
times daily for 7 consecutive days
The 7-day courses of antibiotics or placebo are given after each scheduled
infusion of ADXS11-001, and a 6-month course of antibiotics or placebo is given
during the Lm surveillance monitoring period.
Please also refer to table 5 in the protocol ( page 31)
Study burden and risks
Participation in this study will take a maximum of approximately 6 years.
This duration will include a 1-year treatment period and a 5-year follow-up
period which will include a study visit approximately every 3 months for the
first year and then every 6 months for the remaining 4 years. All visits to the
hospital will last between 2 and 6 hours. The subject will also receive a phone
calls every 3 months during the Post-Disease Recurrence phase
The following procedures will be done during the different visits:
19x full physical examination, 3x focused physical examination, 2x check
medical history, demographics, surgical history, 10x vital signs measurement,
17x pelvic examination, 10x performance status assessment, 22x blood drawn, 9x
urine pregnancy test ( for women of childbearing potential), 18x completion of
quality of life forms, 8x administration of pre-medications, 8 x infusion of
IMP, 8x IV infusion of hydration fluid before each treatment 8x 7 day course of
antibiotics (after each IMP infusion), 17x CT scan of chest and abdomen and MRI
of pelvis, 6 month antibiotic course during Lm surveillance monitoring, 12x
blood draw during Lm surveillance monitoring.
during all visits concomitant medication use is discussed as well as ( serious)
adverse events
The most common side effects with the use of ADXS11-001 are: Headache,
Chills, Fever, Nausea, Vomiting, Feeling physically or mentally exhausted
(Fatigue), Low hemoglobin blood count (Anemia), Pain (abdominal).
Please refer to the patient information leaflet and investigator Brochure for
less common side effects of the IMP and other medications used in this study as
well as Risks Associated With Study Procedures.
College Road East 305
Princeton NJ 08540
US
College Road East 305
Princeton NJ 08540
US
Listed location countries
Age
Inclusion criteria
• Subjects with:
o Histological diagnosis of squamous cell, adenocarcinoma or adenosquamous carcinoma of the cervix who have undergone definitive therapy with a curative intent;• Subjects may have:
o Stage IB2, IIA2, IIB with any of the following pelvic lymph node metastases criteria:
- Biopsy proven pelvic node(s)
- 2 or more positive nodes by MRI/CT >=1.5 cm shortest dimension
- 2 or more positive pelvic nodes by PET with standard uptake value >=2.5
OR
o All Stage IIIA, IIIB, IVA
OR
o Any FIGO stage with para-aortic lymph node metastases criteria (defined by 1 of the following):
- Biopsy proven para-aortic node(s)
- 1 or more positive para-aortic node(s) by MRI/CT >1.5 cm shortest dimension
- 1 or more positive para-aortic node(s) by PET with SUV >2.5;Subjects must have received definitive therapy with curative intent, which consist of at least 4 weeks of treatment with cisplatin and a minimum of 40 Gy external beam radiation therapy (EBRT). NOTE: Brachytherapy is permitted.;• Subjects must be:
o Age 18 years or older
o GOG performance status 0 - 1
o ANC >=1000 x 109/L
o Platelets >=75 x 109/L
o Bilirubin <=1.5 x ULN
o AST or ALT <=2.5 x ULN
o Serum creatinine or measured creatinine clearance <=1.5 xULN
o Toxicities resulting from definitive therapy must resolve to <=Grade 1 prior to randomization, with the exception of peripheral neuropathy (sensory and motor) which must resolve to <=Grade 2.
Exclusion criteria
• Subjects who have not achieved disease-free status (e.g. no evidence of measurable disease or non-measurable disease per RECIST 1.1) after completion of CCRT administered with curative intent.
• Subjects with FIGO stage IVB
• Histologies other than described above (neuroendocrine cancers are excluded)
• Subjects who have 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.
• 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.
• Who are receiving, plan, or anticipate on receiving PI3K or TNF* inhibitors
• Has a contraindication (sensitivity or allergy) to trimethoprim/sulfamethoxazole and ampicillin.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2015-004844-20-NL |
| ClinicalTrials.gov | NCT02853604 |
| CCMO | NL57159.000.17 |