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A Phase I Study of a Therapeutic Vaccine Candidate in Patients With Localized Breast Cancer at High-Risk of Relapse

NCT02364492

Description:

The purpose of this study is to evaluate if a maximum tolerated dose (MTD) can be obtained following 2 administrations of the MAG-Tn3 + AS15 cancer vaccine when administered at doses of 30 µg, 100 µg or 300 µg IM every three weeks.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Phase I Study of a Therapeutic Vaccine Candidate in Patients With Localized Breast Cancer at High-Risk of Relapse
  • Official Title: An Open Label First-in-Human Adjuvant Phase I Study of a Synthetic Multiple Antigenic Glycopeptide Displaying a Tri Tn Glycotop (MAG-Tn3) Plus AS15, as a Therapeutic Vaccine Candidate in Patients With Non Metastatic, HER2 Negative Localized Breast Cancer at High-Risk of Relapse

Clinical Trial IDs

  • ORG STUDY ID: 2014.14
  • NCT ID: NCT02364492

Conditions

  • Breast Neoplasms

Interventions

DrugSynonymsArms
MAG-TN3 + AS15MAG-Tn3 + AS15

Purpose

The purpose of this study is to evaluate if a maximum tolerated dose (MTD) can be obtained following 2 administrations of the MAG-Tn3 + AS15 cancer vaccine when administered at doses of 30 µg, 100 µg or 300 µg IM every three weeks.

Detailed Description

      This study is a three dose level open-label, non-randomized, dose-escalation study Phase I of
      the safety of the vaccine candidate MAG-Tn3 + AS15 administered to patients with HER2
      negative, high-risk localized breast cancer in remission.

      A maximum of 30 patients will be included in the study:

        -  3 or 6 patients in the 1st dose level (30 µg)

        -  6 or 12 patients in the 2nd dose level (100 µg)

        -  6 or 12 patients in the 3rd dose level (300 µg) The clinical study phase I is composed
           of a vaccination period of about 4 months (16 weeks) and a follow-up period of 36 months
           (3 years).

      Each patient will receive one of the three escalating doses of MAG-Tn3 in combination with a
      fixed dose of AS15 adjuvant.

      The subject will receive 6 vaccine injections, administered by intramuscular injection with a
      3-weeks interval between injections. Each patient will be followed 36 months after the last
      injection. The follow-up period is composed of a short-term follow-up period of 6 months and
      a long-term follow-up period of 30 months.

      A total of 20 visits will be required for each patient. Clinical data and blood samples will
      be collected for analysis for each patient.

      Clinical study data will be recorded for each patient on source documentation and then
      entered on electronic CRFs (eCRFs) using a proprietary Electronic Data Capture (EDC) Clinical
      Data Base Software System. The eCRF data are to be entered by site personnel trained in EDC
      data entry.

      A monitor will visit the site regularly to check the completeness of patient records, the
      accuracy of entries on the e-CRFs, the adherence to the protocol and to Good Clinical
      Practice, the progress of enrollment, and to ensure that study drug is being stored,
      dispensed, and accounted for according to specifications.

      Institut Pasteur or designated CRO will conduct data management. Data entered into EDC will
      be housed in a central database. Changes will be tracked to provide an audit trail.
      Interactive data checks will be carried out as applicable during the data entry process.
      Additional data checks are programmed to identify errors in the SAS datasets. Applicable
      queries based on the SAS datasets will be added to EDC for resolution by data management
      personnel. At the conclusion of the study, when all data have been entered and source
      document verified, with no outstanding queries remaining, the Investigator of each site will
      be required to electronically sign each patient's casebook to confirm that the data for each
      patient are complete and accurate and consistent with the patient's source documents. The
      data will then be locked to prevent further editing.

      Concomitant medications entered into the database will be coded using the WHO Drug Reference
      List, which employs the Anatomical Therapeutic Chemical classification system. Medical
      history/current medical conditions and adverse events terminology will be coded using the
      Medical dictionary for regulatory activities.The newest version of the dictionary at data
      base lock will be used.
    

Trial Arms

NameTypeDescriptionInterventions
MAG-Tn3 + AS15Experimental3 escalating doses of MAG-Tn3 in combination with a fixed dose of AS15 adjuvant. For each dose patient will receive 6 injections at 3 interval weeks.
  • MAG-TN3 + AS15

Eligibility Criteria

        Inclusion Criteria:

          1. All patients must have a diagnosis of epithelial breast carcinoma which is, according
             to TNM classification:

               -  Any T

               -  With Positive (N+) or Negative (N-) Lymph-Node depending on the patient profile

               -  And Non metastatic (M0)

          2. HER2/neu-negative (Immunohistochemical expression "0-1+", and/or FISH/CISH "non
             amplified" according to ASCO 2012 criteria)

          3. First line treatment population with a High-Risk of Relapse as defined by:

               -  with at least 4 positive lymph nodes (LN) at primary surgery, or at least one
                  positive lymph node >pN1mi after completion of 6-8 cycles of
                  anthracyclines/taxanes-based neoadjuvant chemotherapy

               -  Or, negative hormone receptors: ER- and PR- , (<10%), i.e "Triple Negative breast
                  cancer" With at least one positive lymph node >pN1mi or negative lymph node if a
                  pathological complete remission was not achieved (persistence of invasive
                  carcinoma) after completion of 6-8 cycles of anthracyclines/taxanes-based
                  neoadjuvant chemotherapy

          4. Patients must have completed all their local and regional treatments including
             adequate surgery and radiation therapy, and at least 6 cycles of chemotherapy
             (neoadjuvant and/or adjuvant) according to institutional and national standards.

          5. The time interval between the end of all the first line standard treatment (completion
             of surgery, chemotherapy and radiation therapy) should be at least 3 months and within
             a maximum of 18 months before inclusion in the study.

        Exclusion Criteria:

          1. Any breast cancer recurrence or metastasis.

          2. Patients with HER2/neu positive breast carcinoma (IHC score 2+ or 3+ and/or
             FISH/CISH-amplified).

          3. Patients with any uncontrolled bleeding disorder including coagulation disorder or
             thrombocytopenia or prothrombotic disorder.

          4. Patients with a personal history of autoimmune disease (including but not limited to
             multiple sclerosis, lupus, rheumatoid polyarthritis, inflammatory bowel diseases,
             Graves' disease and Hashimoto's disease).

          5. Patients with a history of previous anaphylaxis or severe allergic reaction to
             vaccines or other known or unknown allergens.

          6. Patients who have received any commercial vaccine within one month before the first
             dose of study vaccine or are planned to receive any vaccine till 3 weeks after the 6th
             vaccine injection.
      
Maximum Eligible Age:70 Years
Minimum Eligible Age:40 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:To assess the number of patient(s) presenting dose-limiting toxicities (DLTs) from the first vaccine injection in the first patient of the dose cohort till 3 weeks after the second vaccine injection of the last patient of the dose cohort.
Time Frame:3 weeks after 2 study vaccine injections corresponding to visit number 5.
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Institut Pasteur

Trial Keywords

  • [C04.588.180]

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