Evaluation of masitinib combined to gemcitabine, carboplatin or capecitabine in patients with a metastatic or locally advanced breast cancer relapsing after a first chemotherapy treatment

• Register: EUCTR
• Last refreshed on: 30 June 2019
• Main ID: EUCTR2010-022646-24-ES
• Date of registration: 17/12/2014
• Prospective Registration: Yes
• Primary sponsor: AB Science
• Public title: Evaluation of masitinib combined to gemcitabine, carboplatin or capecitabine in patients with a metastatic or locally advanced breast cancer relapsing after a first chemotherapy treatment
• Scientific title: A prospective, multicentre, open-label, randomized, uncontrolled, phase 1/2 study to evaluate efficacy and safety of masitinib in combination with gemcitabine or carboplatin or capecitabine in patients with a metastatic or locally advanced breast cancer (all hormonal status tumor except triple negative tumor) and who relapsed after a first line chemotherapy. - Breast Cancer
• Date of first enrolment: 15/04/2015
• Target sample size: 60
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-022646-24
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: yes; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: Placebo: Other:
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Czech Republic, France, Greece, Italy, Slovakia, Spain

Contacts

• Name: Consuelo Pozo
• Affiliation: Alpha Bioresearch, S.L.

• Name: Consuelo Pozo
• Affiliation: Alpha Bioresearch, S.L.

Key inclusion & exclusion criteria

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.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 24
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30

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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: no

Health Condition(s) or Problem(s) studied

Metastatic or locally advanced breast cancer
MedDRA version: 18.0 Level: LLT Classification code 10027475 Term: Metastatic breast cancer System Organ Class: 100000004864

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: masitinib
Product Code: AB1010
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: masitinib mesylate
CAS Number: 790-299-79-5
Current Sponsor code: AB1010
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
INN or Proposed INN: masitinib mesylate
CAS Number: 790-299-79-5
Current Sponsor code: AB1010
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-

Trade Name: GEMCITABINE ACCORD
Product Name: gemcitabine hydrochloride
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: gemcitabine hydrochloride
CAS Number: 122111-03-9
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2000-

Trade Name: CAPECITABINE
Product Name: capecitabine
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: capecitabine
CAS Number: 154361-50-9
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 150-500

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: week 24

Secondary Objective: 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.

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.

Main Objective: Overall Survival (OS)

Secondary Outcome(s)

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.

Timepoint(s) of evaluation of this end point: Week 6, 12, 18 and 24

Secondary ID(s)

AB10005

Source(s) of Monetary Support

AB Science

Ethics review

Status: Approved
Approval date:
Contact: