A study to assess the effectiveness of the drug lucitanib in lung cancer patients

Phase 1

• Conditions: FGFR1-amplified squamous non-small cell lung cancer (NSCLC); MedDRA version: 16.1Level: PTClassification code 10029522Term: Non-small cell lung cancer stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2013-003874-29-IT
• Lead Sponsor: EOS S.p.A.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-11-22
• Last Update Posted: 26 February 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

1. Male or female patient aged = 18 years
2. Histologically confirmed stage IV squamous NSCLC.
3. FGFR1-amplification determined on the most recent archive sample available or on a newly performed biopsy.
a. FGFR1 amplification may be determined through a study-specific screening or may be known already through a molecular screening program.
b. Patients can be included based on local assessment by Fluorescence In Situ Hybridization [FISH], Comparative Genomic Hybridization [CGH] or Chromogenic In Situ Hybridization [CISH].
c. Confirmatory central reading with FISH is required for determination of the FGFR1 amplification status. The screening status is considered as FGFR1-amplified under at least one of the following conditions:
i. the gene-to-centromere (FGFR1/CEN8) ratio is = 2.0,
ii. the average number of FGFR1 signals per tumour cell nucleus is = 6,
iii. the percentage of tumour cells containing = 15 FGFR1 signals or large clusters is = 10%,
iv. the percentage of tumour cells containing = 5 FGFR1 signals is = 50%
Amplification is deemed to be of low level if (iv) is the sole condition met.
d. Patients in whom the central reading does not confirm amplification can continue the study at the discretion of the treating physician if clinical benefit is observed but have to be replaced.
4. Availability of a tissue sample suitable for the central confirmation by FISH of FGFR1 amplification.
5. Documented progressive extra CNS disease at the time of inclusion.
6. At least one measurable lesion extra CNS according to RECIST 1.1 (with the last objective assessment no more than 4 weeks before the first lucitanib intake).
a. In addition, one prior scan of the measurable lesion(s) performed within maximum 3 months, if available, should be collected to assess tumour kinetics.
7. At least one prior treatment line in the advanced-metastatic setting (including chemotherapy and/or targeted therapy).
8. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
9. Ability to take oral medication.
10. Adequate bone marrow function: ANC = 1.0 x 10E9/L, platelet counts = 100 x 10E9/L and haemoglobin = 9 g/dL.
11. Adequate renal function defined as: calculated clearance = 60 mL/min (assessed with MDRD formula), proteinuria dipstick < 1+. If proteinuria dipstick = 1+, urinary protein over 24 hours should be < 1.0 g/24hrs.
12. Adequate hepatic function defined as: AST, ALT = 3 x UNL (= 5 x UNL in case of liver metastasis); bilirubin < 1.5 x UNL; ALP = 2.5 x UNL (= 5 x UNL in case of bone metastasis).
13. Left ventricular ejection fraction (LVEF) = 50% evaluated by cardiac ultrasound (ECHO) or Multi Gated Acquisition Scan (MUGA).
14. 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.
15. Negative serum pregnancy test during screening for women with childbearing potential within 7 days prior to the first lucitanib intake.
16. For men and women of child-bearing potential, use of a medically accepted method of contraception for the duration of the study and for 6 months after participation in the study.
17. Willingness and ability to give written informed consent and to comply with study procedures as described in section 13.3 of the protocol.
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 ra

Exclusion Criteria

1. Known symptomatic central nervous system (CNS) metastases not controlled by prior surgery or radiotherapy and/or low dose steroids.
2. 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.
3. Cyclical chemotherapy within a period of time that is shorter than the cycle length used for that treatment (e.g. 3 weeks for pemetrexed, cisplatin, navelbine, gemcitabine, docetaxel) before the first dose of lucitanib.
4. Biologic therapy within a period of time that is = 5 T1/2 or = 4 weeks (whichever is shorter) before the first dose of lucitanib.
5. Treatment with a small molecule therapeutics on a continuous or intermittent schedule within a period of time that is = 5 T1/2 or = 4 weeks (whichever is shorter) before the first dose of lucitanib.
6. Involvement in another therapeutic clinical trial at the same time or within 4 weeks prior to consent.
7. Wide field radiotherapy = 4 weeks or limited field radiation for palliation = 2 weeks before the first dose of lucitanib.
8. Tumours that are invading or abutting a major vessel and/or tumours that are cavitary as assessed by CT or MRI.
9. History of major surgical procedure, open biopsy, or significant trauma within 28 days prior to consent.
10. A prior history of hemoptysis = ½ teaspoon (2.5mL) of blood per day for a day or more within 1 week of study treatment.
11. History of gross hemoptysis within 3 months prior to enrolment.
12. History of coagulopathy or haemorrhagic disorders.
13. History of abdominal fistula, GI perforation, or intra-abdominal abscess within 3 month prior to enrolment.
14. Serious non-healing wound, ulcer, or bone fracture.
15. Uncontrolled hypertension (defined as supine systolic blood pressure = 140 mm Hg and/or diastolic blood pressure = 90 mm Hg) despite optimized antihypertensive therapy.
16. Cardiovascular disease or conditions, including:
- Congestive heart failure (New York Heart Association functional classification = 2) or requiring therapy.
- History of myocardial infarction, acute coronary syndromes (including unstable angina), coronary angioplasty and/or stenting within 6 months before the first day of study drug administration.
- Ventricular and/or supra-ventricular arrhythmia requiring therapy.
- Conduction disturbance including QTc prolongation (defined as a QTc interval > 450 ms according to Fridericia’s correction as observed by the investigator) or other significant ECG abnormalities including 2nd degree AV block type II, 3rd degree AV block or bradycardia (HR < 50 bpm); history of severe arrhythmia, or history of familial arrhythmia [e.g., Wolff-Parkinson-White syndrome]).
- Risk factors or unavoidable concomitant treatment with medications known to prolong QTc interval and that may be associated with Torsades de Pointes (see Appendix 4).
17. Patients with thromboembolic events < 12 months prior to treatment start or at high risk of such events.
18. Ongoing treatment with Warfarin or drugs highly bound to plasma protein (see Appendix 5).
19. Significant gastrointestinal abnormalities, including active ulcerative colitis, chronic diarrhoea associated with intestinal malabsorption, Crohn's disease, and/or prior surgical procedures affecting absorption or requirement for intravenous (IV) alimentation.
20. Serious/active bacterial, viral or fungal infection (i

Study & Design

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