A Phase II Clinical Trial of Chemo-radiotherapy in Combination With INO-3112 in Patients With Locally Advanced Cervical Cancer
- Conditions
- Uterine Cervical Neoplasms
- Interventions
- Radiation: Radiotherapy (Extrernal beam radiotherapy + brachytherapy)Biological: INO-3112 vaccine
- Registration Number
- NCT02501278
- Brief Summary
The aim of this study is to assess the potential benefit of the addition of immunotherapy with VGX-3100 and INO-9012 (i.e. INO-3112) to concomitant CRT or, to concomitant CRT and continued as adjuvant in patients with locally advanced cervical cancer.
Safety run-in: To test the safety of CRT combined with immunotherapy with INO-3112. This safety run-in phase will include the first 3 patients treated in each of the two INO-3112 combination arms who are exposed to at least two immunotherapy doses and evaluate whether the combination does not pose undue immediate risks to the patients further enrolled in the trial.
Phase II:To demonstrate sufficient activity in the experimental combination arms to warrant a further phase III conclusive trial based on progression free survival (PFS) at 18 months assessed by RECIST by the local investigator. The efficacy will be assessed within each experimental arm while the standard arm will serve as a reference arm to check the reliability of the results.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- Female
- Target Recruitment
- Not specified
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A: Immunotherapy during and after CRT + vaccine boost Cisplatin chemotherapy INO-3112 dosing during chemoradiotherapy plus immunotherapy dosing after chemoradiotherapy in an adjuvant setting and vaccine boost one year after last vaccine dosing. Arm B: Immunotherapy during CRT + vaccine boost Cisplatin chemotherapy INO-3112 dosing during chemoradiotherapy, and vaccine boost one year after last vaccine dosing. CRT without immunotherapy Cisplatin chemotherapy Standard chemoradiotherapy without immunotherapy CRT without immunotherapy Radiotherapy (Extrernal beam radiotherapy + brachytherapy) Standard chemoradiotherapy without immunotherapy Arm B: Immunotherapy during CRT + vaccine boost Radiotherapy (Extrernal beam radiotherapy + brachytherapy) INO-3112 dosing during chemoradiotherapy, and vaccine boost one year after last vaccine dosing. Arm A: Immunotherapy during and after CRT + vaccine boost Radiotherapy (Extrernal beam radiotherapy + brachytherapy) INO-3112 dosing during chemoradiotherapy plus immunotherapy dosing after chemoradiotherapy in an adjuvant setting and vaccine boost one year after last vaccine dosing. Arm A: Immunotherapy during and after CRT + vaccine boost INO-3112 vaccine INO-3112 dosing during chemoradiotherapy plus immunotherapy dosing after chemoradiotherapy in an adjuvant setting and vaccine boost one year after last vaccine dosing. Arm B: Immunotherapy during CRT + vaccine boost INO-3112 vaccine INO-3112 dosing during chemoradiotherapy, and vaccine boost one year after last vaccine dosing.
- Primary Outcome Measures
Name Time Method Progression free survival (PFS) at 18 months assessed by RECIST 18 months Progression Free Survival at 18 months assessed by local investigator
Occurence of Adverse Events 6 months In order to ensure adequate safety of the combination treatment, a safety run-in will be performed. This safety run-in phase will include the first 3 patients treated in each of the experimental arms (arms A \& B) exposed to at least two immunotherapy doses. The acute safety of the combination of INO-3112 with concomitant CRT will be evaluated similar to a phase I "3+3" safety design. The safety evaluation will be done by the Data Safety Monitoring Board who will invoke an IDMC evaluation of the whole study if undue safety signals are observed.
Acute toxicity is defined as a grade 3 or more related AEs occurring between the first dose of vaccine administration and up to 14 days after the second dose of immunotherapy. Adverse events are graded according to the NCI CTCAE v4.0. Use of narcotics will be reviewed on case-to-case basis by a medical review team to assess its relevance towards the safety evaluation
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
Centre Hospitalier Universitaire Vaudois
🇨🇭Lausanne, Switzerland