A Phase 2 Open-Label Study Evaluating the Efficacy and Safety of Telatinib in Combination with Chemotherapy as First-line Therapy in Subjects with Advanced Gastric CancerEstudio de fase 2, abierto, de evaluación de la eficacia y la seguridad de telatinib en combinación con quimioterapia como tratamiento de primera línea en pacientes con cáncer gástrico avanzado

• Conditions: Patient population includes patients with Advance gastric cancer, with Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1. Patients must have measurable disease and must not have received prior systemic anticancer therapy for advance or metastatic gastric cancer.Indicación: Cáncer Gastrico Avanzado; MedDRA version: 9Level: PTClassification code 10061967Term: Gastric cancer stage IV

• Registration Number: EUCTR2009-010730-21-ES
• Lead Sponsor: ACT BIOTECH, Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-04-21
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 35

Inclusion Criteria

1. Age > 18 years
2. Histologically or cytologically confirmed adenocarcinoma of the stomach or gastro-esophageal junction with inoperable locally advanced or metastatic disease, not amenable to curative therapy
3. At least 1 measurable lesion that has not been irradiated. The lesion will be measured according to Response Evaluation Criteria in Solid Tumors (RECIST), and be documented by radiological evaluation within 28 days prior to study entry
(4. Eastern Cooperative Oncology Group (ECOG) PS of 0 or 1 at study entry
5. Prior radiation therapy completed at least 28 days prior to study entry (if applicable)
6. Adequate bone marrow, liver, and renal function at study entry as assessed by:
? Hemoglobin > 9.0 g/dL (transfusion and growth factor independent)
? Platelet count > 100,000/µL (transfusion independent)
? Absolute neutrophil count (ANC) > 1500/µL (growth
factor independent)
? Total bilirubin < 2.0 times the upper limit of normal
(ULN)
? Alanine aminotransferase (ALT [SGPT]) and aspartate aminotransferase (AST [SGOT]) < 5.0 x ULN in the presence of liver metastasis; ALT [SGPT] and AST [SGOT] < 2.5 x ULN in the absence of liver
metastasis
? International normalized ratio for prothrombin time
(PT-INR) < 1.5 and activated partial thromboplastin
time (aPTT) < 1.5 x ULN. The use of full-dose oral or
parenteral anticoagulants is permitted as long as the INR or aPTT is within therapeutic limits (according to the medical standard in the institution) and the subject has been on a stable dose of anticoagulants for at least two weeks before study entry.
? Serum creatinine < 1.5 times ULN
? Calculated creatinine clearance > 60 mL/min. The
Cockroft and Gault formula (Section 12.7) is
recommended for calculation of creatinine clearance.
Subjects with a calculated creatinine clearance below 60 mL/min may be eligible if a measured creatinine
clearance (based on 24 hour urine collection or other
reliable method) is > 60 mL/min
7. Negative serum pregnancy test performed within 7 days prior to study entry for women of childbearing potential
8. Women and men of childbearing potential must agree to use adequate contraception (e.g., condom, intrauterine device (IUD), oral contraceptive, or double-barrier method), prior to study entry, for the duration of study participation and 28 days
after the last study drug dosing
9. Able and willing to sign a written informed consent. A signed informed consent must be appropriately obtained prior to any study specific procedures.
10. Able to comply with study procedures and follow-up examinations
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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Previous chemotherapy for locally advanced or metastatic gastric cancer. Subjects may have received prior neoadjuvant or adjuvant chemotherapy as long as it was completed at least
6 months prior to study entry.
2. Previous anti-angiogenic therapy (i.e. anti-VEGF or VEGFR tyrosine kinase inhibitor such as bevacizumab, sorafenib,sunitinib, AZD2171)
3. Previous total platinum dose >300 mg/m2 [Total prior platinum dose of <300 mg/m2 will be allowed in the adjuvant or neo-adjuvant setting as long as it was completed at least 6 months prior to study entry]
4. Locally advanced disease that is amenable to curative therapy (including operation and/or chemotherapy and/or radiotherapy)
5. Clinical or radiographic evidence of brain metastasis
6. Cardiac disease defined by:
? Congestive heart failure > class II New York Heart
Association (NYHA) (Section 12.5), or
? Unstable angina (anginal symptoms at rest), or newonset angina (began within the last 12 months), or myocardial infarction within the 12 months prior to
enrolment, or
? Cardiac ventricular arrhythmias requiring antiarrhythmic therapy
? Atrial fibrillation or atrioventricular heart block
7. Uncontrolled hypertension at study entry (systolic blood pressure >150 mmHg or diastolic pressure > 90 mmHg) despite optimal medical management
8. Any (including pulmonary) hemorrhage/bleeding event > grade 3 by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v.3.0 within 28 days prior to study entry
9. Major surgery, open biopsy, or significant traumatic injury within 28 days prior to study entry
10. Current serious, non-healing wound, ulcer, or bone fracture at study entry
11. History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study entry
12. Active clinically serious infection > grade 3 by NCI-CTCAE v.3.0 at study entry
13. Known human immunodeficiency virus (HIV) infection or chronic hepatitis B (HBV) or C (HCV). The safety of telatinib in this subject population has not been studied.
14. Previous or concurrent cancer that is distinct in primary site or histology from gastric cancer. Subjects with cervical cancer in-situ, treated basal cell carcinoma, superficial bladder tumors (Ta and Tis) or any cancer curatively treated > 3 years
prior to study entry are eligible.
15. Anti-cancer therapy (chemotherapy, hormonal therapy, radiation therapy, surgery, immunotherapy, biologic therapy or tumor embolization) or investigational agent within 28 days prior to study entry
16. Known or suspected allergy to any component of telatinib, cisplatin or capecitabine
17. Known dihydropyrimidine dehydrogenase (DPD) deficiency
18. Unable to take oral medications (because of certain circumstances such as malabsorption, difficulty swallowing, or other conditions) that could affect oral intake of capecitabine and telatinib
19. Prior or current history of substance abuse, or medical, psychological, or social condition that in the opinion of the investigator may interfere with the subject?s participation in the study or evaluation of the study result
20. Women who are pregnant or breast-feeding

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: Progression-free survival (PFS);Secondary Objective: Overall survival (OS)<br>Overall response rate (ORR)<br>Safety and tolerability<br>Pharmacokinetics and biomarkers;Primary end point(s): The primary endpoint is PFS. For the primary analysis of PFS, PFS will be measured from<br>the date of first study drug administration to the date of first scan that first documents disease<br>progression according to RECIST or the date of symptomatic deterioration if it occurs prior<br>to progression according to RECIST, or the date of death due to any cause (if occurring<br>before progression). For subjects without documented progression or death at the time of<br>analysis, the date of PFS will be censored at the last date of tumor assessment. If a subject<br>has no tumor assessments after Screening (Baseline), then the subject will be censored at day<br>1.