Trial aimed to find the maximum tolerated dose, the recommended dose and the efficacy of E-3810 in patients with advanced solid tumors.

Phase 1

• Conditions: Dose escalation: solid tumors failing standard therapy. Dose-expansion: solid tumors A) with FGFR1 amplification and for breast cancer ? 1 prior endocrine therapy if ER+ or ? 1 chemotherapy otherwise; or B) progressing after SD ? 6 months or PR to prior antiangiogenic treatment; or C) potentially sensitive to antiangiogenic treatment if no antiangiogenic agents available for that specific condition.; MedDRA version: 20.0Level: LLTClassification code 10049280Term: Solid tumourSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2010-019121-34-ES
• Lead Sponsor: Institut de Recherches Internationales Servier

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2011-01-05
• Last Update Posted: 28 May 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 130

Inclusion Criteria

1. Age ? 18 years
2. Histologically or citologically confirmed, locally advanced or metastatic solid tumour, relapsed or refractory to standard therapy.
In addition, only for the dose-expansion phase:
i) solid tumour bearing FGFR1 amplification and, if breast cancer, with at least one prior endocrine therapy in the metastatic setting if ER+, and at least one chemotherapy line otherwise
or
ii) solid tumour progressing after having experienced SD (lasting for at least six month) or PR as best response to prior treatment with an approved or investigational antiangiogenic drug (e.g.: sorafenib, sunitinib, bevacizumab) as a single agent or in a chemotherapy combination
or
iii) solid tumour potentially sensitive to antiangiogenic treatments provided no antiangiogenic agents are approved and\or available for that specific condition.
3. Life expectancy ? 3 months
4. 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
5. 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)
6. Eastern Co-operative Oncology Group (ECOG) performance status ? 1
7. Negative serum pregnancy test at screening in women of child bearing potential
8. For men and women of child-bearing potential, use of a medically accepted method of contraception (abstinence, barrier method with spermicide, intrauterine device, or steroidal contraceptive for women and barrier method for men) for the duration of the study and for 60 days after participation in the study
9. Willingness and ability to give written informed consent and to comply with study procedures
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 86
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 44

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 requiring therapy
- Ventricular and/or supra-ventricular arrhythmia requiring therapy
- Severe conduction disturbance (including QTc interval prolongation > 0.47 sec [corrected], history of severe arrhythmia, or history of familial arrhythmia [e.g., Wolff-Parkinson-White syndrome])
- Angina pectoris requiring therapy
- Left ventricular ejection fra-tion (LVEF) < 50% evaluated by cardiac ultrasound (ECHO) or Multi Gated Acquisition Scan (MUGA)
- Uncontrolled hypertension (defined as systolic blood pressure ? 140 mm Hg and/or diastolic blood pressure ? 90 mm Hg with optimized antihypertensive therapy)
- Myocardial infarction (MI) within 6 months prior to administration of the first dose
- > Class I cardiovascular disease according to the New York Heart Association's (NYHA) Functional Criteria
6. Ongoing treatment with Warfarin
7. Unavoidable concomitant treatment with any drug known for potential risk of causing Torsades de Pointes (see list in Appendix 4)
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
13. Known hypersensitivity to gelatin or lactose monohydrate
14. Difficulty with swallowing
15. Pregnant or lactating women.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified