E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Newly diagnosed histologically confirmed high risk HER2-negative breast cancer candidate for neoadjuvant chemotherapy |
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E.1.1.1 | Medical condition in easily understood language |
Newly diagnosed high risk breast cancer candidate for preoperative chemotherapy |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10006190 |
E.1.2 | Term | Breast cancer invasive NOS |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To investigate the activity of EndoTAGTM-1 + paclitaxel combination therapy in patients with Her2-negative BC candidate for neoadjuvant chemotherapy, as measured by the decrease in MRI-estimated tumour volume at the end of EndoTAGTM-1 + paclitaxel administration vs. baseline. |
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E.2.2 | Secondary objectives of the trial |
To evaluate: • Reduction in tumor size as defined by MRI-measured greatest diameter(s) following RECIST criteria at the end of EndoTAGTM-1 + paclitaxel administration • Decrease in MRI-estimated tumor perfusion at the end of EndoTAGTM-1 + paclitaxel administration • Pathological complete response (pCR) • Rate of residual cancer burden at time of surgery • Safety and tolerability of the neoadjuvant regimen • Rate of breast-conserving surgery (BCS) • Rate of clinical complete and partial responses (CR, PR) • Rate of lymph node-negative disease after treatment (node-NEG) To collect frozen tumor biopsies at baseline and surgery for future translational research on DNA and RNA
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. newly diagnosed histologically confirmed BC with breast infiltrating carcinoma of histological grade > 1 (either operable, or locally advanced or inflammatory) candidate for neoadjuvant chemotherapy 2. Her2-negative tumor, defined according to immunohistochemistry or using fluorescent in-situ hybridization (FISH) 3. ECOG performance status 0 or 1 4. Gender: female 5. Age 18 years old 6. Negative pregnancy test (females of childbearing potential) 7. Willingness to perform double-barrier-contraception during study and for 6 months post chemotherapy treatment (females of childbearing potential) 8. Signed informed consent
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E.4 | Principal exclusion criteria |
1. Metastatic or relapsed disease 2. Major surgery < 3 weeks prior to enrollment 3. Severe pulmonary obstructive or restrictive disease 4. Uncontrolled inflammatory disease (autoimmune or infectious) 5. Clinically significant cardiac disease (NYHA stadium > 2) 6. Results of laboratory tests (hematology, chemistry) outside specified limits: • WBC ≤ 3 x 109/L • ANC < 1.5 x 109/L • Platelets < 100 x 109/L • Hb ≤ 9.0 g/dl (≤ 5.6 mmol/l) • PTT/ INR > 1.5 x ULN • AST or ALT > 2.5 x ULN • Alkaline Phosphatase > 2 x ULN • Total Bilirubin > 1.5 x ULN 7. Pregnancy or nursing status 8. Known positive HIV testing 9. Known hypersensitivity to any component of the EndoTAGTM-1, taxane or FEC formulations 10. History of malignancy other than breast cancer < 5 years prior to enrollment, except skin cancer (i.e. basal or squamous cell carcinoma) treated locally 11. History of active or significant neurological disorder or psychiatric disorder that would prohibit the understanding and giving of informed consent, or would interfere in the clinical and radiological evaluation of central nervous system during the trial 12. Concurrent treatment with other experimental products. Participation in another clinical trial with any investigational product within 30 days prior to study entry
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E.5 End points |
E.5.1 | Primary end point(s) |
The percent reduction in MRI-estimated tumor volume at the end of EndoTAGTM-1 + paclitaxel administration vs. baseline. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The end of EndoTAGTM-1 + paclitaxel administration |
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E.5.2 | Secondary end point(s) |
• The percent reduction in linear tumour size as measured on MRI by the greatest linear diameter(s) of the tumour following RECIST criteria at the end of EndoTAGTM-1 + paclitaxel administration • The percent reduction in MRI-estimated tumour perfusion at the end of EndoTAGTM-1 + paclitaxel administration • Pathological complete response (pCR) is defined as the absence of any residual invasive cancer in the breast and the absence of any metastatic cells in the regional lymph nodes at the time of surgery (University of Texas MD Anderson Cancer Center trial’s pCR criteria) • Residual cancer burden (RCB) scores are calculated according to the RCB index proposed by Symmans et al (2007) • Rate of breast-conserving surgery (BCS) • Rate of clinical complete and partial responses (CR, PR) • Rate of lymph node-negative disease after treatment (node-NEG)
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The end of EndoTAGTM-1 + paclitaxel administration Surgery |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |