Evaluation of masitinib in patients with advanced ovarian cancer

• Register: EUCTR
• Last refreshed on: 14 September 2015
• Main ID: EUCTR2013-000491-14-GB
• Date of registration: 18/08/2014
• Prospective Registration: No
• Primary sponsor: AB Science
• Public title: Evaluation of masitinib in patients with advanced ovarian cancer
• Scientific title: A prospective, multicenter, open-label, centrally allocated, active-controlled, phase 2/3 study to evaluate the efficacy and safety of masitinib in combination with gemcitabine versus gemcitabine alone in advanced/metastatic epithelial ovarian cancer patients in second line being refractory to first line platinum treatment or in third line. - Phase 2 comparing masitinib with gemcitabine in ovarian cancer v1
• Date of first enrolment: 08/08/2014
• Target sample size: 80
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-000491-14
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: yes Other trial design description: prospective, active-controlled, seamless adaptive If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Austria, Czech Republic, France, Germany, Greece, Spain, United Kingdom, United States

Contacts

• Name: Igor Antonshchuk/Project Manager
• Affiliation: AB Science

• Name: Igor Antonshchuk/Project Manager
• Affiliation: AB Science

Key inclusion & exclusion criteria

Inclusion criteria:
1. Female patient, with histologically or cytologically confirmed advanced / metastatic epithelial ovarian cancer either:
a. first line platinum-refractory ovarian cancer (progression during first-line platinum-based chemotherapy)
b. first line platinum-resistant ovarian cancer (relapsing within 6 months after the end of first-line chemotherapy)
c. candidate to third line treatment (refractory or resistant to 2nd line platinum-based therapy or patients who progressed after other type of chemotherapy in 2nd line).
2. Patient has recovered of all acute toxic side effects of prior therapy or surgical procedures to grade = 1 Common Toxicity Criteria for Adverse Event (CTCAE v4.03), except for the laboratory values
3. Patient has at least one target lesion that can be measured in one dimension, according to the Response Evaluation Criteria in Solid Tumors (RECIST)
4. ECOG Performance status = 2
5. Patient with adequate organ function
a. Absolute neutrophils count (ANC) = 1.5 x 109/L
b. Haemoglobin = 10 g/dl
c. Platelets (PLT) = 75 x 109/L
d. AST and ALT = 3 x ULN (= 5 x ULN in case of liver metastases)
e. Gamma GT = 2.5 x ULN (= 5 x ULN in case of liver metastases)
f. Bilirubin = 1.5x ULN (= 3xULN in case of liver metastases)
g. Normal Creatinine or if abnormal creatinine, creatinine clearance = 50 mL/min (Cockcroft and Gault formula)
h. Albuminaemia > 1 x LLN
i. Proteinuria < 30 mg/dL (1+) on the dipstick. If proteinuria is = 1+ on the dipstick, 24 hours proteinuria must be < 1.5g/24 hours
6. Patient with life expectancy > 3 months
7. Patient weight> 40 kg and BMI > 18 Kg/m2
8. Female patient = 18 years
9. Patient with nutritional risk index (NRI) = 83.5, i.e. with no or moderate malnutrition; NRI is calculated as follows: NRI = 1.519 x serum albumin level + 0.417 x (current weight / basic weight) x 100
- serum albumin in g/L
- basic weight calculation with Lorentz formula for ideal BW for women: (height - 100) - ((height - 150)/2)
- serum albumin in g/L
- basic weight calculation with Lorentz formula for ideal BW for women: (height - 100) - ((height - 150)/2)
10. Female patient of childbearing potential (entering the study after a menstrual period and who have a negative pregnancy test), who agrees to use two highly effective methods (one for the patient and one for the partner) of medically acceptable forms of contraception during the study and for 3 months after
the last treatment intake. Acceptable forms of contraception include:
· A documented placement of an intrauterine device (IUD) or intrauterine system (IUS) and the useof a barrier method (condom or occlusive cap [diaphragm or cervical/vault caps] used with spermicidal foam/gel/film/cream/suppository);
· Documented tubal ligation (female sterilisation). In addition, a barrier method (condom or occlusive cap [diaphragm or cervical/vault caps] used with spermicidal
foam/gel/film/cream/suppository) should also be used;
· Double barrier method: Condom and occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository;
· Any other contraceptive method with a documented failure rate of <1% per year;
· Abstinence when this is in line with the preferred and usual lifestyle of the patient.
11. Patient able and willing to comply with study visits and procedures as per protocol
12. Patient is able to understand, sign, and date the written informed consent form at the screening visit prior to any protocol-specific procedures performed.
13. Patient able to
Exclusion criteria:
EXCLUSION CRITERIA
A patient must not be enrolled if she fulfils one of the following exclusion criteria:
1. Patient intolerant to gemcitabine
2. Patient who has not recovered from any significant treatment toxicities prior to baseline (=Grade 2)
3. Patient presenting with cardiac disorders defined by at least one of the following conditions:
a) 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)
b) Patient with cardiac failure class III or IV of the NYHA classification
c) Patient with severe conduction disorders which are not prevented by permanent pacing (atrioventricular block 2 and 3, sino-atrial block)
d) Syncope without known aetiology within 3 months
e) Uncontrolled severe hypertension, according to the judgment of the investigator, or symptomatic hypertension
4. Pregnant or nursing female patient
5. Patient with active central nervous system (CNS) metastasis or with history of CNS metastasis
6. Patient treated for a cancer other than epithelial ovarian cancer within 5 years before enrolment, with the exception of basal cell carcinoma or cervical cancer in situ
7. 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
WASH-OUT
1. Patient who had any major surgery within 4 weeks before baseline/W0
2. Patient treated with any investigational agent within 4 weeks prior baseline
3. Patient who had systemic chemotherapy within 4 weeks before baseline
4. Patient who had radiotherapy within 4 weeks before baseline



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

Health Condition(s) or Problem(s) studied

Advanced / metastatic epithelial ovarian cancer patients in second line being refractory to first line platinum treatment or in third line
MedDRA version: 18.0 Level: PT Classification code 10033158 Term: Ovarian epithelial cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

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

Intervention(s)

Product Name: Masitinib
Product Code: AB 1010
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Mastinib mesylate
CAS Number: 790-200-79-5
Current Sponsor code: AB1010
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 119-238

Trade Name: Gemcitabine
Product Name: Gemcitabine
Pharmaceutical Form: Powder for infusion
INN or Proposed INN: Gemcitabine
CAS Number: 95058-81-4
Other descriptive name: SUB07892MIG
Concentration unit: mg/m2 milligram(s)/square meter
Concentration type: range
Concentration number: 750-1000

Primary Outcome(s)

Secondary Objective: The primary endpoint is overall survival (OS) of the patient. Secondary objectives includes:
Secondary endpoints
• Survival rate every 6 months
• Progression Free Survival (PFS)
• PFS rate week every 8 weeks
• Time To Progression (TTP)
• TTP rate every 8 weeks
• Best response rate during the study,
• Disease control rate (CR + PR + SD)
• Tumor biomarkers levels (CA 125)
• Quality of Life every 8 weeks
• Pharmacogenomic assessment of selected genes
• Safety profile using the CTCAE v4.03 classification

Main Objective: The objective is to compare the efficacy and safety of masitinib in combination with gemcitabine versus gemcitabine alone in advanced / metastatic epithelial ovarian cancer patients in second line being refractory to first line platinum treatment or in third line.

Timepoint(s) of evaluation of this end point: Time from baseline to documented death.

Primary end point(s): Overall Survival (OS)

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Disease control rate, CA 125 and Quality of Life will be evaluated at Baseline, Week 8 and every 8 Weeks after W 8 and at the end of study visit.

Secondary end point(s): Secondary endpoints
• Survival rate every 6 months
• Progression Free Survival (PFS)
• PFS rate week every 8 weeks
• Time To Progression (TTP)
• TTP rate every 8 weeks
• Best response rate during the study,
• Disease control rate (CR + PR + SD)
• Tumor biomarkers levels (CA 125)
• Quality of Life every 8 weeks
- according to the EORTC QLQ-C30 questionnaire
- ECOG Performance Status
- Analgesic intake
- Pain improvement (VAS)
• Pharmacogenomic assessment of selected genes
• Safety profile using the CTCAE v4.03 classification

Secondary ID(s)

2013-000491-14-ES

AB12008

120579

Source(s) of Monetary Support

AB Science