advanced or metastatic hepatocellular, ovarian, renal cell and gastric carcinomas in patients who have progressed after standard therapies
Conditions
Interventions
Product Name: tasquinimod
Product Code: ABR-215050
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: tasquinimod
CAS Number: 25496
Sponsors
Ipsen Pharma
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: All Patients: 1. Able and willing to provide written informed consent and to comply with the study protocol and procedures 2. Age =18 years 3. ECOG performance status 0 or 1 4. Life expectancy greater than 3 months in the Investigator’s opinion 5. Disease progression during or after previous cancer treatment 6. Measurable disease as per RECIST Criteria (v1.1) 7. The following time must have elapsed between previous therapy for cancer and first administration of tasquinimod: - At least 2 weeks since previous systemic targeted therapy with small molecule inhibitors, which includes any tyrosine-kinase inhibitor - At least 4 weeks since the last dose of systemic anti-cancer therapy other than targeted therapy, which includes cytotoxic agents, monoclonal antibody therapy, immunotherapy and prior radiotherapy - At least 1 week since prior hormonal therapy - At least 3 months since prior interferon therapy 8. Recovery to Grade 1 from the effects (excluding alopecia) of any prior therapy for their malignancies 9. At least 4 weeks since any major surgery or open biopsy and 7 days since a core biopsy before first study treatment 10. Adequate renal function: - Creatinine =1.5 times upper limit of normal (ULN) or calculated creatinine clearance (CrCl) using the Cockcroft Gault formula =60 mL/min or measured CrCl =60 mL/min 11. Adequate hepatic function: - Serum bilirubin =1.5 mg/dL (=25 µmol/L) for OC, RCC and GC, serum bilirubin =3 mg/dL (=50 µmol/L) for HCC - Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =2.5 x ULN (=5 x ULN if liver lesions present i.e. liver metastasis or primary tumour of the liver for HCC) 12. Adequate bone marrow function: - Absolute neutrophil count =1.5 x 10E9/L - Platelets =50 x 10E9/L - Haemoglobin =90 g/L 13. Adequate coagulation tests: international normalised ratio (INR) =1.5 x ULN 14. Able to swallow capsules 15. For women of childbearing potential, a negative pregnancy test must be documented prior to first administration of study treatment 16. For women who are not postmenopausal (12 months of amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to use adequate methods of contraception (e.g., hormonal implants, combined oral contraceptives, vasectomised partner), during the treatment period and for at least 3 months after the last dose of study treatment 17. For men: agreement to use a barrier method of contraception during the treatment period and for at least 3 months after the last dose of study treatment HCC H18. Histologically confirmed and documented HCC (excluding fibrolamellar carcinoma) H19. Barcelona Clinic Liver Cancer (BCLC) stage C or BCLC stage B not amenable to locoregional therapy or refractory to locoregional therapy H20. Liver mass measuring at least 2 cm with characteristic vascularisation seen on either triphasic computed tomography (CT) scan or magnetic resonance imaging (MRI) with gadolinium H21. At least one m
Exclusion criteria
Exclusion criteria: All Patients: 1. Other primary malignancy within the past 3 years (except for fully-resected non-melanoma skin cancer, localised prostate cancer with normal prostate specific antigen level, or cervical cancer in situ) 2. Known central nervous system metastasis that is symptomatic and/or requires treatment 3. Malabsorption (other than in patients with GC and partial or complete gastrectomy) or intestinal obstruction 4. History of pancreatitis 5. Essential medications that are known potent inhibitors or inducers of cytochrome P450 (CYP) 3A4 6. Ongoing treatment with CYP1A2 (including warfarin) or CYP3A4 metabolised drug substance with narrow therapeutic range at the start of study. Treatment with low molecular weight heparin (LMWH) is permitted 7. History of myocardial infarction, unstable angina, congestive heart failure New York Heart Association class III/IV, cerebrovascular accident, transient ischaemic attack, limb claudication at rest in the previous 6 months, or ongoing symptomatic dysrhythmias, or uncontrolled atrial, or ventricular arrhythmias, or uncontrolled hypertension defined as systolic blood pressure =150 mmHg or diastolic blood pressure =90 mmHg 8. Evidence of bleeding diathesis or known coagulopathy 9. History of venous thromboembolic disease within 3 months prior to first administration of study treatment 10. The patient has current, severe and uncontrolled medical condition such as infection, diabetes mellitus or other systemic disease 11. Any condition or illness that, in the opinion of the Investigator or the medical monitor, would compromise patient safety or interfere with the evaluation of the safety of the drug 12. Has known positive serology for human immunodeficiency virus 13. Investigational drug within 28 days or within five times the elimination half-life (whichever is longest) prior to first dose of study treatment 14. Known allergy to treatment medication or its excipients. 15. Breastfeeding Hepatocellular Carcinoma (Cohort H) H15. Fibrolamellar carcinoma. Ovarian Carcinoma (Cohort O) O15. Non-epithelial cancer and borderline tumours (e.g., tumours of low malignant potential). Gastric Carcinoma (Cohort G) G15. Other histologic type than adenocarcinoma.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): The primary efficacy endpoint is the proportion of patients who have neither progressed nor died (PFS rate) as measured by RECIST v1.1; Timepoint(s) of evaluation of this end point: PFS rate at: • Cohort H (HCC) - 16 weeks • Cohort O (OC) - 24 weeks • Cohort R (RCC) - 16 weeks • Cohort G (GC) - 12 weeks ; Main Objective: To determine the clinical activity of tasquinimod in advanced or metastatic hepatocellular, ovarian, renal cell and gastric carcinomas in patients who progressed after standard therapies Clinical activity will be measured by the proportion of patients who have neither progressed nor died at a prespecified timepoint (progression free survival [PFS] rate): • In advanced or metastatic hepatocellular carcinoma (HCC) after one line of sorafenib • In advanced or metastatic ovarian carcinoma (OC) resistant to platinum containing therapy • In metastatic renal cell carcinoma (mRCC) previously treated with vascular endothelial growth factor (VEGF) inhibitor • In advanced or metastatic gastric carcinoma (GC) after one line of platinum containing therapy. ; Secondary Objective: In each tumour cohort: • To determine the activity and other clinical endpoints such as PFS, response rate, time to progression (TTP), and overall survival • To evaluate the safety and tolerability of tasquinimod • To assess the tolerability of a starting dose of 0.5 mg/day of tasquinimod • To characterise the pharmacokinetics (PK) of tasquinimod in each tumour cohort, particularly female patients, patients with gastre | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy Endpoints 1. Proportion of patients who have neither progressed nor died (PFS rate) at 16 weeks measured by Choi criteria in Cohort H. 2. Response rate defined by RECIST v1.1 for all cohorts (also Choi criteria for Cohort H) at futility and final analysis timepoints 3. Clinical benefit per cohort: complete response + partial response + stable disease lasting =12 weeks 4. PFS defined as the time from first study treatment to progression or death due to any cause 5. Time to progression 6. Overall survival defined as the time from first study treatment to death due to any cause. Safety Endpoints 1. Complete physical examination including the evaluation of performance status using ECOG, body weight and vital signs 2. AEs and laboratory abnormalities as characterised using the NCI CTCAE v4.03 and SAEs 3. Clinical laboratory assessments 4. Dose reductions and discontinuations for toxicity and tolerability 5 ECG. Pharmacokinetic Endpoints 1. A limited and targeted PK sampling strategy and a population PK analysis of concentration/time data using the Nonlinear Mixed Effects Modelling Tool (NONMEM) software (version 6.0 or above) 2. An estimate of exposure at steady state (AUCss) and summarised by cohort, where appropriate. ; Timepoint(s) of evaluation of this end point: Efficacy: 1 & 2. Tumour assessments at each visit 3, 4 & 5. PFS & TTP and OS assessed throughout study Safety: 1 - 4. Assessed at each study visit 5. ECG at screening or baseline, weeks 2 and 4, end-of-study treatment, and as clinically indicated. PK 1 & 2. PK samples at baseline, weeks 2, 4, 6 and | — |
Countries
Belgium, Canada, France, Spain, United Kingdom
Contacts
Public ContactVP Worldwide Clinical Development
Ipsen Pharma
Outcome results
None listed