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.

• Register: EUCTR
• Last refreshed on: 21 September 2015
• Main ID: EUCTR2013-000491-14-FR
• Date of registration: 07/02/2014
• Prospective Registration: Yes
• Primary sponsor: AB Science
• Public title: 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.
• Scientific title: A prospective, multicenter, open-label, centrally allocated, active-controlled, phase 2 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.
• Date of first enrolment: 12/03/2014
• Target sample size: 56
• 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: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: yes Other specify the comparator: Gemcitabine Number of treatment arms in the trial: 2

Countries of recruitment

Argentina, Austria, Belgium, Czech Republic, France, Germany, Italy, Spain, United Kingdom, United States

Contacts

• Name: Said Bouseida
• Affiliation: AB Science

• Name: Said Bouseida
• Affiliation: AB Science

Key inclusion & exclusion criteria

Inclusion criteria:
1. Female patient, with histologically or cytologically confirmed advanced / metastatic epithelial ovarian cancer either :
a. refractory to first line platinum treatment (i.e. progression or stable disease within a 6 months first line platinum treatment period), or
b. candidate to third line treatment.
2. Patient has recovered of all acute toxic side effects of prior therapy or surgical procedures to grade = 1 National Cancer Institute-Common Toxicity Criteria (NCI-CTCAE v4.02), 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/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. Albumin > 1 x LLN
i. Urea < 2 x ULN
j. 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
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
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 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.
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. If the patient is deemed by the treating physician to be cognitively impaired or questionably impaired in such a way that the ability of the patient to give informed consent is questionable, the designated legal guardian must sign the informed consent
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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 40
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 16

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 (atrio-ventricular 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


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

Health Condition(s) or Problem(s) studied

Advanced/metastatic epithelial ovarian cancer in second line being refractory to first line platinum treatment or in third line
MedDRA version: 16.1 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: AB1010
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: masitinib mesylate
CAS Number: 790299-79-5
Current Sponsor code: AB1010
Other descriptive name: MASITINIB
Concentration unit: mg/kg milligram(s)/kilogram
Concentration type: equal
Concentration number: 100-
INN or Proposed INN: masitinib mesylate
CAS Number: 790299-79-5
Current Sponsor code: AB1010
Other descriptive name: MASITINIB
Concentration unit: mg/kg milligram(s)/kilogram
Concentration type: equal
Concentration number: 200-

Primary Outcome(s)

Main Objective: Overall survival (OS)

Secondary Objective: • 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 NCI-CTCAE v4.02 classification

Primary end point(s): Overall Survival (OS) is defined as the time from the randomization to the date of documented death death due to any cause.

Timepoint(s) of evaluation of this end point: Date of documented death

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Every 8 weeks

Secondary end point(s): • Survival rate is defined as the proportion of patients alive at each time point
• Overall Progression Free Survival (PFS) is defined as the time from the randomization to the date of documented progression or any cause of death during the study.
Progression will be assessed by CT scan according to RECIST criteria version 1.1 as defined in Table 5.
• PFS rate is defined as the proportion of patients without progression or death at each time point
• Overall Time To Progression (TTP) is defined as the time from the randomization to the date of documented progression defined according to RECIST criteria version 1.1
• TTP rate is defined as the proportion of patients without progression at each time point
• Best response is defined as best response across all time points during treatment period.
• Disease control rate (CRR ) is calculated as the number of patients with documented partial response, complete response or stable disease (CR + PR + SD) defined according to RECIST criteria version 1.1, divided by the number of patients allocated at each time point.

Secondary ID(s)

AB12008

2013-000491-14-ES

Source(s) of Monetary Support

AB Science