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

Phase 1

Conditions: advanced or metastatic hepatocellular, ovarian, renal cell and gastric carcinomas in patients who have progressed after standard therapies
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2012-002326-75-BE

Lead Sponsor: Ipsen Pharma

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 200

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 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 (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 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

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.