| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Metastatic or locally advanced breast cancer |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| 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 | 18.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10027475 |
| E.1.2 | Term | Metastatic breast cancer |
| E.1.2 | System Organ Class | 100000004864 |
|
| 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 |
|
| E.2.2 | Secondary objectives of the trial |
o Survival rate every 6 weeks until week 24 and every 12 weeks thereafter
? Tumour assessment:
o Overall Progression Free Survival (PFS)
o PFS rate every 6 weeks until week 24 and every 12 weeks thereafter
o Overall Time to progression (TTP)
o TTP rate every 4 weeks
o Objective response rate (CR + PR) every 6 weeks until week 24 and every 12 weeks thereafter
o Control disease rate (CR + PR + SD) at week every 6 weeks until week 24 and every 12 weeks thereafter
o Best response during study treatment
? Level of serum CA 15-3 every 6 weeks until week 24 and every 12 weeks thereafter.
? Quality of life assessment according to the EORTC QLQ-C30 questionnaire every 6 weeks until week 24 and every 12 weeks after
? ECOG Performance Status every 6 weeks until week 24 and every 12 weeks after
? Safety profile using the NCI CTC v4.02 classification
? Pharmacokinetics
? CDA activity and pharmacogenomic analysis. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Patient with histologically or cytologically confirmed metastatic or locally advanced breast cancer
2. Patient with Hormone Receptor (ER and PR) ? positive and/or negative and/or unknown status; HER2-positive and/or negative and/or unknown status (patients who have both unknown or negative HR and HER2 status, are not eligible for the study)
3. At least one measurable lesion as defined by the Response Evaluation Criteria in Solid Tumors (RECIST)
4. Patient with progression after a first line of treatment in locally advanced/metastatic setting (a line of treatment is defined as at least one normal cycle of chemotherapy) with antracycline and/or taxane (or trastuzumab-based if HER2+)
5. Patient eligible for receiving a second line chemotherapy including gemcitabine, carboplatin and capecitabine.
6. ECOG Performance status ?2
7. Patient with adequate organ function:
? Absolute Neutrophils Count (ANC) ?1.5 x 109/L
? Haemoglobin ?10 g/dL
? Platelets (PTL) ? 75 x 109/L
? AST/ALT ?3 x ULN (?5 x ULN in case of liver metastases)
? Gamma-GT ? 2.5 x ULN (?5 x ULN in case of liver metastases)
? Bilirubin ?1.5 x ULN (?3x ULN in case of liver metastases)
? Normal creatinine or if abnormal creatinine, creatinin clearance ?50 mL/min (Cockcroft and Gault formula)
? Albumin >1 xLLN
? Proteinuria < 30 mg/dL (1+) on the dipstick; if proteinuria is ? on the dipstick, 24 hours proteinuria must be <1.5g/24 hours
8. Patient with life expectancy >3 months
9. Female patient, age >18 years
10. Patient weight > 40 kg and BMI >18
11. Female patient of child bearing potential who agrees to use a method of medically acceptable forms of contraception during the study and 3 months after the last intake of study treatment
12. Patient able and willing to comply with study visits and procedures as per protocol
13. Patient able to understand the patient card and to follow the patient card procedures in case of signs or symptoms of severe neutropenia or severe cutaneous toxicity, during the first 2 months of treatment.
14. Patient able to understand, sign, and date the written informed consent form at the screening visit prior to any protocol-specific procedures are performed
15. Patient affiliated to a social security regimen. |
|
| E.4 | Principal exclusion criteria |
1. Patient intolerant to gemcitabine or carboplatin or capecitabine
2. Prior hormonal therapy only as treatment for metastatic disease without chemotherapy. Patients must have received chemotherapy for their metastatic disease in the first-line setting. Hormone therapy alone is not allowed
3. Treatment with more than one prior cytotoxic regimen for metastatic breast disease
4. Patient with Triple Negative metastatic breast cancer
5. 5. Patient presenting with cardiac disorders defined by at least one of the following conditions:
? Patient with recent cardiac history (within 6 months) of:
- Acute coronary syndrome
- Acute heart failure (class III or IV of the NYHA classification)
- Significant ventricular arrhythmia (persistent ventricular tachycardia, ventricular fibrillation, resuscitated sudden death)
? Patient with cardiac failure class III or IV of the NYHA classification
? Patient with severe conduction disorders which are not prevented by permanent pacing (atrio-ventricular block 2 and 3, sino-atrial block)
? Syncope without known aetiology within 3 months
? Uncontrolled severe hypertension, according to the judgment of the investigator, or symptomatic hypertension
6. Pregnant or nursing female patient
7. Patient presenting at least a grade II peripheral neuropathy
8. Patient treated for a cancer other than breast cancer within 5 years before enrolment, with the exception of basal cell carcinoma or cervical cancer in situ
9. Patient with active central nervous system (CNS) metastasis (i.e. nonprogressive after surgery and/or radiotherapy and/or radiosurgery, without steroids and antiepileptic requirements)
10. Patient with history of poor compliance or history of drug/alcohol abuse, or excessive alcohol beverage consumption that would interfere with the ability to comply with the study protocol, or current or past psychiatric disease that might interfere with the ability to comply with the study protocol or give informed consent
? Previous treatment
11. Patient treated with any investigational agent within 4 weeks prior baseline. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Overall Survival (OS) is defined as the time from the randomization to the date of documented death due to any cause. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
? Survival
o Survival rate at week 6, 12, 18, 24
? Tumour assessment:
o Overall Time to progression (TTP)
o PFS rate every 6 weeks until week 24 and every 12 weeks thereafter
o TTP rate every 4 weeks
o Objective response rate (CR + PR) every 6 weeks until week 24 and every 12 weeks thereafter
o Control disease rate (CR + PR + SD) at week every 6 weeks until week 24 and every 12 weeks thereafter
o Best response during study treatment
? Level of serum CA 15-3 every 6 weeks until week 24 and every 12 weeks thereafter.
? Quality of life assessment according to the EORTC QLQ-C30 questionnaire every 6 weeks until week 24 and every 12 weeks after
? ECOG Performance Status every 6 weeks until week 24 and every 12 weeks after
? Safety profile using the NCI CTC v4.02 classification
? Pharmacokinetics
? CDA activity and pharmacogenomic analysis. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
|
| 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 | 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 | 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 | 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) | Information not present in EudraCT |
| E.8.2.2 | Placebo | Information not present in EudraCT |
| E.8.2.3 | Other | Information not present in EudraCT |
| 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.8.4.1 | Number of sites anticipated in Member State concerned | 15 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 20 |
| 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 | Yes |
| 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
|
| Patient could be treated until disease progression, limiting toxicity or consent withdrawal |
|
| 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 | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| 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 | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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