E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Adenocarcinoma of the breast that is HER2 negative. |
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E.1.1.1 | Medical condition in easily understood language |
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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 | PT |
E.1.2 | Classification code | 10006187 |
E.1.2 | Term | Breast cancer |
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 compare the progression free survival (PFS) between the YM155 plus Docetaxel and the Docetaxel regimen. |
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E.2.2 | Secondary objectives of the trial |
• Objective response rate (ORR)
• Overall survival (OS)
• Duration of response (DOR)
• Clinical benefit rate (CBR)
• Time to response (TTR)
• Safety and tolerability |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
The pharmacogenomic sub-study is included in the main protocol.
Study objectives are to comprehensively analyze:
• Suspected disease-related genes such as oncogenes, survivin and vascular
endothelial growth factor (VEGF)
• Genes potentially involved in drug excretion and/or metabolism such as the organic
anion/cation transporters (OAT, OCT)
• Genes of relevance to toxicity/safety issues, to be identified in a precautionary /
retrospective setting |
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E.3 | Principal inclusion criteria |
A subject is eligible for the study if all of the following apply:
1. The subject prior to any study-related procedures (including withdrawal of prohibited medicines, if applicable) has provided Institutional Review Board (IRB)-/Independent Ethics Committee (IEC)- approved written Informed Consent and privacy language as per national regulations (e.g., HIPAA Authorization for US sites).
2. The subject is male or female and aged 18 years or older at the Baseline Visit with
metastatic breast cancer.
3. The subject has histologically- or cytologically-proven adenocarcinoma of the
breast that is HER2 negative defined as one of the following:
o Negative fluorescence in-situ hybridization (FISH).
o 0 or 1+ immunohistochemistry (IHC).
o IHC 2+ with negative FISH.
Subjects with hormone receptor positive or negative status are eligible. Additionally,
subjects with triple negative status (meaning estrogen receptor negative, rogesterone receptor negative and HER2 negative) are eligible.
4. The subject has received no prior chemotherapy regimen for metastatic breast cancer.
o Prior treatment with a cytotoxic therapy (other than docetaxel) is allowed if
administered in the neoadjuvant or adjuvant setting >3 weeks prior to the Baseline
Visit, with all side effects of using prior cytotoxic therapy resolved or back to
baseline (with the exception of weight loss or gain, anorexia, alopecia or fatigue).
o Prior treatment with docetaxel is allowed if administered in the neoadjuvant or
adjuvant setting, and the subject has no recurrent disease within 12 months after
completing treatment, with all side effects of prior docetaxel use resolved or back to
baseline (with the exception of weight loss or gain, anorexia, alopecia or fatigue).
o Prior treatment with a kinase inhibitor, biologic therapy, vaccine, or investigational treatment other than cytotoxic therapy or procedure for breast cancer is allowed if administered in the neoadjuvant, adjuvant or metastatic setting ≥ 4 weeks prior to the Baseline Visit.
o Prior treatment with hormonal therapy in the neoadjuvant, adjuvant or metastatic setting is allowed if administered ≥ 2 weeks prior to the Baseline Visit.
o Prior treatment with bevacizumab is allowed if administered in the neoadjuvant or adjuvant setting >4 weeks prior to the Baseline Visit.
5. Prior palliative radiation therapy is allowed if treatment was completed ≥ 2
weeks prior to the Baseline Visit with side effects from radiation resolved.
6. The subject has an Eastern Cooperative Oncology Group (ECOG) performance
status ≤ 1 at the Baseline Visit.
7. The subject has at least one measurable lesion by RECIST (Version 1.1).
o If the selected lesion(s) received prior radiation and/or loco-regional therapy,
there must be evidence of disease progression since the last radiation or
locoregional therapy.
8. If the subject has a previous history of non-breast cancer malignancy, the subject must meet the following criteria for a cancer survivor:
o Subject having a previous history of a non-invasive carcinoma is eligible if in the opinion of the Investigator, he/she has successful curative treatment anytime prior to enrollment.
o For all other malignacies, the subject has undergone potentially curative therapy and the subject has been considered disease free for at least 5 years.
9. The subject’s life expectancy is estimated to be > 12 weeks at the Baseline Visit.
10. The subject must be non-pregnant and non-lactating. Each site will administer a
pregnancy test to any female of childbearing potential during the Screening
Period and at the Baseline Visit. Only subjects with negative pregnancy test
results will be eligible. All sexually active subjects of childbearing potential must
agree to use an adequate method of contraception throughout the study period. |
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E.4 | Principal exclusion criteria |
A subject will be excluded from participation if any of the following apply:
1. The subject has hypersensitivity to docetaxel or polysorbate 80.
2. The subject has had a major surgical procedure, substantial open biopsy, or significant traumatic injury within 28 days prior to the Baseline Visit or anticipation of need for major surgical procedure during the course of the study.
3. The subject has neuropathy ≥ Grade 2 at the Baseline Visit.
4. The subject has inadequate marrow, hepatic and/or renal function at the Baseline Visit defined as:
o Serum creatinine ≥ 1.5 x ULN or calculated serum creatinine clearance < 60
mL/min.
o ANC < 1500/mm3.
o Platelets ≤ 100,000/mm3.
o Alanine Transaminase (ALT) or Aspartate Transaminase (AST) >2.5 x ULN, or
>5 x ULN in subjects who have documented liver metastases.
o Bilirubin > ULN.
o Hemoglobin <9 gm/dL
5. Known brain or leptomeningeal metastasis as assessed through medical history review and physical examination.
6. The subject has a known history of positive test for Hepatitis B surface Antigen
(HsbAg) or hepatitis C antibody or history of positive test for Human
Immunodeficiency Virus (HIV).
7. The subject has significant and/or uncontrolled cardiac, renal, hepatic or other
systemic disorders or significant psychological conditions at Baseline Visit that in
the Investigator’s judgment would jeopardize subject enrollment or compliance
with the study procedures. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint for the study is progression free survival (PFS). PFS is defined as the time from the date of randomization until objective tumor progression or death. Objective tumor progression includes radiological assessments by independent reviewers blinded for the treatment assignment. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
After 67 Progression Free Events have been observed in the study. |
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E.5.2 | Secondary end point(s) |
- Objective response rate
- Overall survival
- Duration of response
- Clinical benefit rate
- Time to response
- Safety and Tolerability |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
After 67 Progression Free Events have been observed in the study. |
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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 | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Potential efficacy biomarkers |
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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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 24 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Russian Federation |
United States |
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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
|
End of study reflects when the last subject receives the last survival
contact. The End of Study date could include a study visit, successful
telephone contact, etc. Definition provided in the protocol. |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 14 |