A randomised, double-blind, phase III efficacy and safety study of cediranib (RECENTIN™ ) when added to cisplatin plus a fluoropyrimidine, compared with cisplatin plus a fluoropyrimidine alone, in patients with previously untreated, locally advanced or metastatic, unresectable Gastric Cancer (GC)

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2009-016468-35-HU
• Date of registration: 23/02/2010
• Prospective Registration: Yes
• Primary sponsor: AstraZeneca AB
• Public title: A randomised, double-blind, phase III efficacy and safety study of cediranib (RECENTIN™ ) when added to cisplatin plus a fluoropyrimidine, compared with cisplatin plus a fluoropyrimidine alone, in patients with previously untreated, locally advanced or metastatic, unresectable Gastric Cancer (GC)
• Scientific title: A randomised, double-blind, phase III efficacy and safety study of cediranib (RECENTIN™ ) when added to cisplatin plus a fluoropyrimidine, compared with cisplatin plus a fluoropyrimidine alone, in patients with previously untreated, locally advanced or metastatic, unresectable Gastric Cancer (GC)
• Date of first enrolment: 14/07/2010
• Target sample size: 730
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-016468-35
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: Placebo: yes Other:

Countries of recruitment

Hungary

Key inclusion & exclusion criteria

Inclusion criteria:
1. Provision of informed consent prior to any study specific procedures
2. Female or male aged 18 years or older
3. Histological or cytological confirmation of gastric adenocarcinoma (including the gastric cardia and esophagogastric junction)
4. Locally advanced or metastatic gastric cancer. In patients with locally advanced disease the cancer must be considered unresectable
5. Patients must have received no prior systemic therapy for advanced disease. Neoadjuvant and adjuvant therapy received > 6 months prior to entry into the study is acceptable
6. WHO Performance score of 0 or 1
7. Able to take oral medication
8. Life expectancy = 12 weeks
9. At least one lesion (measurable or non measurable) that can be accurately assessed by CT or MRI at baseline and follow-up visits.
For inclusion in the optional genetic research and biomarker analysis components of the study (blood and archival tumour sampling for DNA extraction and retrospective pharmacogenetic analysis and tumour biomarker analysis), patients must fulfil the following criteria:
10. Provision of written informed consent for blood sampling for genetic research
and/or
11. Provision of written informed consent for tumour biomarker analysis

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.Untreated unstable brain or meningeal metastases. Patients with radiological evidence of stable brain metastases are eligible providing that they are asymptomatic and either do not require corticosteroids or have been treated with corticosteroids, with clinical and radiological evidence of stabilisation at least 10 days after discontinuation of steroids
2.Inadequate bone marrow reserve as demonstrated by an absolute neutrophil count =1.5 x 10*9/L or platelet count =100 x 10*9/L or requiring regular blood transfusions to maintain haemoglobin >8.5g/dL
3.Serum bilirubin = 1.5 x ULRR (except for patients with known documented cases of Gilbert’s syndrome)
4.Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) = 2.5 x ULRR. If liver metastases are present, ALT or AST > 5 x ULRR
5.Serum creatinine > ULRR or a creatinine clearance of = 60mL/min calculated by Cockcroft-Gault
6.Greater than +1 proteinuria on two consecutive dipsticks taken no less than 1 week apart unless urinary protein < 1.5g in a 24 hr period or protein/creatinine ratio < 1.5
7.A history of poorly controlled hypertension or resting BP >150/100 mmHg in the presence or absence of a stable regimen of anti-hypertensive therapy (measurements will be made after the patient has been resting supine for a minimum of 5 minutes. Two or more readings should be taken at 2-minute intervals and averaged. If the first two diastolic readings differ by more than 5 mmHg, then an additional reading should be obtained and averaged)
8.Any evidence of severe or uncontrolled systemic diseases (eg, unstable or uncompensated respiratory, cardiac, hepatic or renal disease)
9.Any unresolved toxicity >CTC grade 1 from previous systemic anti-cancer therapy (including radiotherapy) except haematological toxicity (see exclusion #2) and alopecia
10.Mean QTc with Bazetts correction >470msec in screening ECG or history of familial long QT syndrome
11.Recent (<14 days) major thoracic or abdominal surgery prior to entry into the study, or a surgical incision that is not fully healed
12.Pregnant or breast-feeding women or women of childbearing potential with a positive pregnancy test prior to receiving study medication
13.Known severe hypersensitivity to cediranib, capecitabine (or TS-1 in Japan), cisplatin or any of the excipients of these products
14.History of other malignancies (except for adequately treated basal or squamous cell carcinoma or carcinoma in situ) within 5 years, unless the patient has been disease free for 2 years and there is a tissue diagnosis of advanced gastric adenocarcinoma from a non-target lesion
15.Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
16.Previous enrolment or randomisation in the present study
17.Treatment with an investigational (non-registered) drug within 30 days prior to the first dose of cediranib
18.Other concomitant anti-cancer therapy (including luteinising hormone releasing hormone [LHRH] agonists) except steroids
19.Prior cisplatin therapy within 6 months of the first dose of cediranib
20.Total previous culmulative dose of cisplatin exceeding 300mg/m2
21.Prior therapy with monoclonal antibodies or small molecule inhibitors against VEGF or VEGF receptors, including bevacizumab and cediranib
22.Known DPD (dihydropyrimidine dehydrogenase) deficiency
23.Known neuropathy > Grade 2
24.History of significant gastrointestinal impairment, as judged by the Investigator, that would

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Gastric cancer
MedDRA version: 12.1 Level: LLT Classification code 10017758 Term: Gastric cancer
MedDRA version: 12.1 Level: LLT Classification code 10017760 Term: Gastric cancer NOS
MedDRA version: 12.1 Level: LLT Classification code 10017766 Term: Gastric cancer stage IV NOS
MedDRA version: 12.1 Level: LLT Classification code 10017767 Term: Gastric cancer stage IV with metastases
MedDRA version: 12.1 Level: LLT Classification code 10017768 Term: Gastric cancer stage IV without metastases
MedDRA version: 12.1 Level: LLT Classification code 10061967 Term: Gastric cancer stage IV
MedDRA version: 12.1 Level: LLT Classification code 10063916 Term: Metastatic gastric cancer

Intervention(s)

Product Name: RECENTIN
Product Code: AZD2171
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: CEDIRANIB
CAS Number: 288383-20-0
Current Sponsor code: AZD2171
Other descriptive name: RECENTIN
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 15-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Product Name: RECENTIN
Product Code: AZD2171
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: CEDIRANIB
CAS Number: 288383-20-0
Current Sponsor code: AZD2171
Other descriptive name: RECENTIN
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 20-
Pharmaceutical form of the placebo: Film-coated tablet
Route of administration of the placebo: Oral use

Primary Outcome(s)

Main Objective: To determine the efficacy of cediranib when added to cisplatin plus a fluoropyrimidine compared to cisplatin plus a fluoropyrimidine alone by assessment of overall survival (OS).

Primary end point(s): Overall survival, defined as the time from randomisation until death by any cause.

Secondary Objective: ·To determine the efficacy of cediranib when added to cisplatin plus a fluoropyrimidine compared to cisplatin plus a fluoropyrimidine alone by assessment of progression free survival (PFS), objective response rate and duration of response.
·To determine the safety and tolerability of cediranib when added to cisplatin plus a fluoropyrimidine compared to cisplatin plus a fluoropyrimidine alone.
·To determine the effects of cediranib when added to cisplatin plus a fluoropyrimidine compared to cisplatin plus a fluoropyrimidine alone on the global health status/QoL scale of the EORTC QLQ-C30 questionnaire.
·To investigate the pharmacokinetics of cediranib when added to cisplatin plus a fluoropyrimidine.

Secondary ID(s)

D8480C00067