Study of Oral E-3810, a Dual VEGFR-FGFR Tyrosine Kinase Inhibitor, in Patients With Solid Tumors

Inclusion Criteria:

1. Age ≥ 18 years
2. Histologically or cytologically confirmed, locally advanced or metastatic solid tumour, relapsed or refractory to standard therapy. Only for the dose-expansion phase:(i) breast cancer, with FGFR1 amplification with at least one prior endocrine therapy in the metastatic setting if ER+, and at least one chemotherapy line otherwise or (ii) tumour progressing after at least one line of treatment with an antiangiogenic drug (e.g.: sorafenib, sunitinib, bevacizumab) as a single agent or in a chemotherapy combination
3. One or more lesion suitable for DCE-MRI and for DCE-US evaluation
4. Life expectancy ≥ 3 months
5. Full recovery (to Grade ≤ 1) from any prior surgical procedure(s) and from reversible side effects of prior therapy for cancer including radiation therapy, chemotherapy, and immunotherapy
6. Adequate haematologic function (haemoglobin ≥ 9 g/dL, absolute neutrophil count [ANC] ≥ 1500/mL, platelets ≥ 100,000/mL), adequate renal function (serum creatinine < 1.5 mg/dL or creatinine clearance > 40 mL/min), and adequate hepatic function (serum bilirubin ≤ 1.5 x upper limit of normal (ULN) mg/dL, aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 3 x ULN)
7. ECOG performance status ≤ 1
8. Negative serum pregnancy test at screening
9. For men and women of child-bearing potential, use of a medically accepted method of contraception

Exclusion Criteria:

1. Active central nervous system (CNS) metastases not controlled by prior surgery or radiotherapy and/or low dose steroids
2. Haematologic malignancies (including leukaemia of any form, lymphoma, and multiple myeloma)
3. Active second malignancy or history of another malignancy within 2 years, with the exception of non-melanoma skin cancers or carcinoma in situ (CIS) of the breast or cervix or controlled, superficial carcinoma of the bladder
4. Treatment with any anticancer agent within 3 weeks, including investigational agents, chemotherapy, immunotherapy, biologic or hormonal therapy, surgery or radiation therapy (6 weeks for nitrosoureas, mitomycin or bevacizumab); luteinizing hormone releasing hormone (LHRH) agonist for prostate and mitotane for adrenal carcinoma are allowed.
5. Significant cardiovascular disease or condition including: congestive heart failure, ventricular and/or supra-ventricular arrhythmia, severe conduction disturbance (including QTc interval prolongation > 0.47 sec), history of severe arrhythmia, or history of familial arrhythmia, angina pectoris, LVEF < 50%, uncontrolled hypertension (systolic blood pressure ≥ 140 mm Hg and/or diastolic blood pressure ≥ 90 mm Hg with optimized antihypertensive therapy), myocardial infarction within 6 months prior to administration of the first dose, > Class I cardiovascular disease according to the NYHA Functional Criteria
6. Ongoing treatment with Warfarin
7. Unavoidable concomitant treatment with any drug known for potential risk of causing Torsades de Points
8. Significant gastrointestinal abnormalities, including ulcerative colitis, chronic diarrhoea associated with intestinal malabsorption, Crohn's disease, and/or prior surgical procedures affecting absorption or requirement for intravenous (IV) alimentation
9. Known pre-existing clinically significant disorder of the hypothalamic-pituitary axis, thyroid and adrenal gland
10. Serious/active bacterial, viral or fungal infection (including known active human immunodeficiency virus [HIV] infection) requiring systemic treatment
11. Concurrent severe or uncontrolled medical disease or organ system dysfunction which, in the opinion of the Investigators, would limit life expectancy to < 3 months, compromise the patient's safety, or interfere with evaluation of the safety of the investigational product
12. Psychiatric disorder or altered mental status that would preclude understanding of the informed consent process and/or completion of the necessary study procedures