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A Phase II Clinical Trial of Chemo-radiotherapy in Combination With INO-3112 in Patients With Locally Advanced Cervical Cancer

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ClinicalTrials.gov Identifier: NCT02501278
Recruitment Status : Withdrawn (company (Inovio) is no longer able to support the study)
First Posted : July 17, 2015
Last Update Posted : May 13, 2016
Sponsor:
Collaborators:
Inovio Pharmaceuticals
Centre Hospitalier Universitaire Vaudois
Information provided by (Responsible Party):
European Organisation for Research and Treatment of Cancer - EORTC

Tracking Information
First Submitted Date  ICMJE July 7, 2015
First Posted Date  ICMJE July 17, 2015
Last Update Posted Date May 13, 2016
Study Start Date  ICMJE May 2016
Estimated Primary Completion Date May 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 15, 2015)
  • Occurence of Adverse Events [ Time Frame: 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
  • Progression free survival (PFS) at 18 months assessed by RECIST [ Time Frame: 18 months ]
    Progression Free Survival at 18 months assessed by local investigator
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02501278 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase II Clinical Trial of Chemo-radiotherapy in Combination With INO-3112 in Patients With Locally Advanced Cervical Cancer
Official Title  ICMJE A Phase II Clinical Trial of Chemo-radiotherapy in Combination With INO-3112 in Patients With Locally Advanced Cervical Cancer
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Uterine Cervical Neoplasms
Intervention  ICMJE
  • Biological: INO-3112 vaccine

    INO-3112 i.e. the combination of VGX-3100 and INO-9012, specifically:

    • VGX-3100 (HPV16 and HPV18 E6-E7 DNA vaccine) will be administered at 3 mg per plasmid (6 mg total DNA)
    • INO-9012 (IL-12 DNA plasmid) will be administered at 1 mg per dose will be administered using the CELLECTRA® electoporation device
  • Radiation: Radiotherapy (Extrernal beam radiotherapy + brachytherapy)

    The whole pelvis will be irradiated with 45 - 50.4 Gy in 25-28 fractions in fractions of 1.8 Gy over 5 weeks daily.

    Those patients with pelvis positive and/or para-aortic positive lymph nodes should be treated with an elective dose to the para-aortic area of 45 Gy in fractions of 1.6-1.8 Gy in 25-28 fractions.

    Pelvic and para-aortic nodes known to contain gross/macroscopically visible disease and heavily involved parametria or tumor areas that may lie beyond the high-dose range of brachytherapy should be treated with additional small volume boost of EBRT to a total dose of 60-65 Gy using a combination of either sequential and/or concomitant boost. Fractions of 1.8-2 Gy can be used in the sequential boost.

  • Drug: Cisplatin chemotherapy
    Cisplatin chemotherapy will be administered i.v. at a dose of 40 mg/m2 (total 5 cycles during week 1-5) weekly in concomitance with RT with the total dose not to exceed 70 mg per week.
Study Arms  ICMJE
  • Experimental: Arm A: Immunotherapy during and after CRT + vaccine boost
    INO-3112 dosing during chemoradiotherapy plus immunotherapy dosing after chemoradiotherapy in an adjuvant setting and vaccine boost one year after last vaccine dosing.
    Interventions:
    • Biological: INO-3112 vaccine
    • Radiation: Radiotherapy (Extrernal beam radiotherapy + brachytherapy)
    • Drug: Cisplatin chemotherapy
  • Experimental: Arm B: Immunotherapy during CRT + vaccine boost
    INO-3112 dosing during chemoradiotherapy, and vaccine boost one year after last vaccine dosing.
    Interventions:
    • Biological: INO-3112 vaccine
    • Radiation: Radiotherapy (Extrernal beam radiotherapy + brachytherapy)
    • Drug: Cisplatin chemotherapy
  • Active Comparator: CRT without immunotherapy
    Standard chemoradiotherapy without immunotherapy
    Interventions:
    • Radiation: Radiotherapy (Extrernal beam radiotherapy + brachytherapy)
    • Drug: Cisplatin chemotherapy
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: May 12, 2016)
0
Original Estimated Enrollment  ICMJE
 (submitted: July 15, 2015)
126
Estimated Study Completion Date  ICMJE May 2021
Estimated Primary Completion Date May 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Main inclusion criteria:

Registration step

  • Age 18 years or older;
  • Newly diagnosed locally advanced cervical cancer defined as FIGO 2009: stage IB2, IIA&IIB, IIIA&IIIB or IVA disease;
  • No evidence of distant metastases (Stage IVB);
  • Histological diagnosis of squamous cell carcinoma, adenocarcinoma or adenosquamous cell carcinoma of the cervix is accepted. Not accepted are small cell, clear cell and other rare variants of the classical adenocarcinoma;
  • Availability of HPV 16 and HPV 18 testing;
  • No HIV seropositive, Hepatitis B or C (unless sustained virologic response achieved by anti-HCV therapy);
  • Written informed consent must be given according to ICH/GCP, and national/local regulations

Randomization step

  • Positive for HPV 16 and/or HPV 18 as assessed by central lab;
  • WHO/ECOG performance status 0 - 2
  • Adequate hematological, liver and renal functions
  • ECG with no clinically significant findings as assessed by the investigator performed within 30 days of signing the informed consent form
  • Absence of current malignancies at other sites, with the exception of adequately treated basal or squamous cell carcinoma of the skin. Cancer survivors, who have undergone potentially curative therapy for a prior malignancy, who have no evidence of that disease for five years and are deemed at low risk for recurrence, are eligible for the study;
  • No prior history of clinically significant autoimmune disease, Crohn's disease, ulcerative colitis;
  • No history of previous therapeutic HPV vaccination (individuals who have been immunized with licensed prophylactic HPV vaccines (e.g. Silgard®, Cervarix®, Gardasil®) are not excluded);
  • No known or suspected hypersensitivity to component(s) of investigational product or cisplatin contraindication (e.g. peripheral neuropathy ≤ grade 2 or ototoxicity ≤ grade 2 as per CTCAE v4);
  • No previous pelvic RT;
  • No previous chemotherapy for this tumor;
  • No patients who have undergone a previous hysterectomy or will have a hysterectomy as part of their initial cervical cancer therapy;
  • No receipt of any immunotherapy within 4 weeks of start of protocol treatment;
  • No prior major surgery within 4 weeks of randomization from which the patient has not recovered.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Switzerland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02501278
Other Study ID Numbers  ICMJE EORTC-1411
2015-004602-42 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party European Organisation for Research and Treatment of Cancer - EORTC
Study Sponsor  ICMJE European Organisation for Research and Treatment of Cancer - EORTC
Collaborators  ICMJE
  • Inovio Pharmaceuticals
  • Centre Hospitalier Universitaire Vaudois
Investigators  ICMJE
Study Chair: Fernanda Herrera Centre Hospitalier Universitaire Vaudois - Lausanne
Study Chair: George Coukos Centre Hospitalier Universitaire Vaudois - Lausanne
PRS Account European Organisation for Research and Treatment of Cancer - EORTC
Verification Date May 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP