A study with tasquinimod, treating patients with hepatocellular, ovarian, renal cell and gastric cancers.

• Register: EUCTR
• Last refreshed on: 26 October 2015
• Main ID: EUCTR2012-002326-75-ES
• Date of registration: 02/10/2012
• Prospective Registration: Yes
• Primary sponsor: Ipsen Pharma
• Public title: A study with tasquinimod, treating patients with hepatocellular, ovarian, renal cell and gastric cancers.
• Scientific title: A multicentre, open label, early stopping design, proof of concept study with tasquinimod in treating patients with advanced or metastatic hepatocellular, ovarian, renal cell and gastric carcinomas.
• Date of first enrolment: 20/12/2012
• Target sample size: 200
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2012-002326-75
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no

Countries of recruitment

Belgium, Canada, France, Spain, United Kingdom

Contacts

• Name: VP Worldwide Clinical Development
• Affiliation: Ipsen Pharma

• Name: VP Worldwide Clinical Development
• Affiliation: Ipsen Pharma

Key inclusion & exclusion 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,
- 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) ?60 mL/min or measured CrCl ?60 mL/min
11. Adequate hepatic function:
- Serum bilirubin ?1.5 mg/dL (?25 ?mol/L) for OC, RCC and GC, serum bilirubin ?3 mg/dL (?50 ?mol/L) for HCC
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ?2.5 x ULN (?5 x ULN if liver lesions present)
12. Adequate bone marrow function:
- Absolute neutrophil count ?1.5 x 109/L
- Platelets ?50 x 109/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 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. BCLC stage C or 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 CT scan or MRI with gadolinium
H21. At least one measurable or evaluable lesion that is viable (i.e. vascularised), and has not been previously treated with locoregional therapy. A lesion that has been previously treated will qualify as a measurable or evaluable lesion if there was demonstrable progression following locoregional therapy
H22. Child-Pugh A Class only
H23. Previously treated with sorafenib. Patients may have experienced radiographically documented disease progression during sorafenib therapy or after discontinuation of sorafenib therapy
H24. The patient has received sorafenib as the most recent systemic
therapeutic intervention
H25. Signed additional consent for a maximum of two liver biopsies during the study
OC
O18. Histologically confirmed and documented ovarian epithelial, fallopian tube, or primary peritoneal cavity cancer
O19. Progression within 6 months of a platinum containing chemotherapy regimen
O20. Progression after up t
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.
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.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

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

advanced or metastatic hepatocellular, ovarian, renal cell and gastric carcinomas in patients who have progressed after standard therapies

Intervention(s)

Product Name: tasquinimod
Product Code: ABR-215050
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: tasquinimod
CAS Number: 254964-60-8
Current Sponsor code: ABR-215050
Concentration unit: mg milligram(s)
Concentration type: range
Concentration number: 0.25-1

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: PFS rate at:
? Cohort H (HCC) - 16 weeks
? Cohort O (OC) - 24 weeks
? Cohort R (CCR) - 16 weeks
? Cohort G (GC) - 12 weeks

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
gastrectomy and patients with cirrhosis Child-Pugh A.

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.

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 (all cohorts) and Choi criteria (Cohort H)

Secondary Outcome(s)

Secondary end point(s): Efficacy Endpoints
1. Response rate defined by RECIST v1.1 for all cohorts (also Choi criteria for Cohort H) at futility and final analysis timepoints
2. Clinical benefit per cohort: complete response + partial response + stable disease lasting ?12 weeks
3. PFS defined as the time from first study treatment to progression or death due to any cause
4. Time to progression
5. 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 12

Secondary ID(s)

2012-002326-75-GB

8-55-58102-004

Source(s) of Monetary Support

Ipsen Pharma