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Trial registered on ANZCTR


Registration number
ACTRN12610000440022
Ethics application status
Approved
Date submitted
20/05/2010
Date registered
1/06/2010
Date last updated
12/07/2012
Type of registration
Retrospectively registered

Titles & IDs
Public title
CLEMENT Capecitabine-radiosensitizing Lutetium-177 octreotate endoradiotherapy management of endocrine neurogenic tumours

Response and Toxicity Assessment
Scientific title
CLEMENT Capecitabine-radiosensitizing Lutetium-177 octreotate endoradiotherapy management of endocrine neurogenic tumours

Response and Toxicity Assessment
Secondary ID [1] 251825 0
Nil
Universal Trial Number (UTN)
Nil
Trial acronym
CLEMENT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neuroendocrine tumour 257424 0
Neuroendocrine malignancy 257425 0
Condition category
Condition code
Cancer 257571 257571 0 0
Neuroendocrine tumour (NET)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a single arm study and all patients receive the same combination regimen as follows: Lutetium -177 octreotate radiopeptide therapy with radiosensitizing chemotherapy. Capecitabine/temozolomide
Lutetium-177 octreotate: 4 cycles at 8 week intervals
7.8 GBq per cycle intravenously on day 1
Capecitabine 1650 mg per metre squared daily for 14 days each 8 weeks for 4 cycles, oral formulation
Temozolomide 200 mg per metre squared once daily for 5 days each 8 weeks for 4 cycles, oral formulation. Every patients receives a standard amino acid solution and standard anti-nausea treatment.
Intervention code [1] 256526 0
Treatment: Other
Intervention code [2] 256559 0
Treatment: Drugs
Comparator / control treatment
No standard treatment of NET exists
Outcomes will be compared to those reported in the published literature for example the recent South Australian Review of Neuroendocrine Tumour Treatment.
The single centre seminal study of Lutetium-177 octreotate radiopeptide therapy of NET as a single agent from the Erasmus Medical Centre, Rotterdam, The Netherlands reported by: Kwekkeboom et al. will be used as the definitive historical comparator since we use the same activity of the same radiopharmaceutical over the same number of cycles in patients with the same eligibility criteria.
Kwekkeboom DJ, de Herder WW, Kam BL et al. Treatment with the radiolabeled somatostatin analog [177 Lu-DOTA 0, Tyr 3] Octreotate: Toxicity, Efficacy and Survival. J Clin Oncol 26:2124-2130, 2008
Control group
Historical

Outcomes
Primary outcome [1] 258488 0
progression-free survival
measurement of target lesions on computer tomography, magnetic resonance imaging (CT/MRI) using standard Response Evaluation in Solid Tumours (RECIST) criteria version 1.1 2009
Timepoint [1] 258488 0
objective response rate evaluation at 1 year from commencement of therapy
Primary outcome [2] 258529 0
Progression-free survival measurement of target lesions on CT/MRI using standard RECIST criteria version 1.1 2009
Timepoint [2] 258529 0
Actuarial survival 1,2,3 years from commencement of treatment.
Secondary outcome [1] 264276 0
overall survival as determined by direct individual patient follow-up by the Investigators
Timepoint [1] 264276 0
actuarial survival 1, 2 3 years from commencement of treatment
Secondary outcome [2] 264289 0
toxicity is assessed according to National Cancer Institute Common Terminology Criteria for Adverse Events version 3 (CTCAE)
Timepoint [2] 264289 0
3 years from commencement of treatment. Myelotoxicity fortnightly for 2 months.Nephrotoxicity 6 monthly for 3 years.

Eligibility
Key inclusion criteria
progressive disseminated unresectable well-differentiated neuroendocrine tumours
Minimum age
18 Years
Maximum age
90 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
impaired renal function, poor performance status, poorly differentiated tumours, inadequate cardiac and hepatic function, impaired haemopoetic reserve platelets less than 100 neutrophils less than 1.5. Chemotherapy within 2 months. Residence outside Western Australia.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
referral by patient's oncologist to the principal investigators
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
physician-sponsored study
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
26/07/2006
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
75
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment postcode(s) [1] 2907 0
6160

Funding & Sponsors
Funding source category [1] 257008 0
Government body
Name [1] 257008 0
Government of WA Cancer Network
Country [1] 257008 0
Australia
Primary sponsor type
Hospital
Name
Fremantle Hospital Health Service
Address
Fremantle Hospital, Alma Street, Fremantle WA 6160
Country
Australia
Secondary sponsor category [1] 256270 0
None
Name [1] 256270 0
Address [1] 256270 0
Country [1] 256270 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 259030 0
Human Research Ethics Committe South Metropolitan Area Health Service
Ethics committee address [1] 259030 0
Fremantle Hospital
Alma Street, Fremantle WA 6160
Ethics committee country [1] 259030 0
Australia
Date submitted for ethics approval [1] 259030 0
25/01/2006
Approval date [1] 259030 0
17/05/2006
Ethics approval number [1] 259030 0
1/06/0201
Ethics committee name [2] 259083 0
Human Research Ethics Committee, South Metropolitan Area Health Serivce
Ethics committee address [2] 259083 0
Fremantle Hospital
Alma Street, Fremantle WA 6160
Ethics committee country [2] 259083 0
Australia
Date submitted for ethics approval [2] 259083 0
19/01/2009
Approval date [2] 259083 0
27/02/2009
Ethics approval number [2] 259083 0
9/01/2010

Summary
Brief summary
177Lu-Octreotate is synthesized from [DOTA,Tyr3]Octreotate labelled with 177LuCl3 (7.8 GBq) distributed by IBD (Baarle-Nassau, the Netherlands). Each patient receives an infusion of aminoacids (Baxter Synthamin) containing 11.6g lysine and 23g arginine/L at 250 ml/hr. Thirty minutes later the radiolabelled somatostatin analogue is co-infused via a side-line over 10-20 minutes. Routine antiemetic therapy is given in the form of Tropisetron (5mg) intravenous (IV) bolus and oral Lorazepam (2mg). The chemotherapy with oral Capecitabine 1650mg/m2 will be reduced to 1500mg/m2 (in line with the American Society of Clinical Oncology (ASCO) dosage), for 14 consecutive days, and commenced on the morning of radionuclide therapy. Cycles will repeated each 8 weeks at the time of each subsequent radionuclide infusion. Temozolomide will be introduced on a dose escalation schedule, in cohorts of 3 patients, commencing at 100mg/m2 for 5 days. A standard dose escalation trial design will be followed with 3 patients completing 2 cycles at the starting dose (100mg/m2) prior to escalation to 150mg/m2 in the next 3 patient cohort. The ultimate maximum dose will not exceed the 200mg/m2 safe level established in the ASCO protocol. In the absence of toxicity all subsequent patients will be treated at this level
All of the previously monitoring, including weekly blood testing and 2 monthly scanning, will remain unchanged from the original CLEMENT protocol.

Assessments: Computer Tomography (CT) or Magnetic Resonance Imaging (MRI) will be performed at baseline and then at each new treatment cycle (8 weeks). Quantitative uptake of 177Lu-octreotate in the tumours will be measured by serial whole body imaging at 4, 24, 48 hours and 5 days and graded according to a 4 point visual scale.
Trial website
Trial related presentations / publications
Phillip G. Claringbold , Paul A. Brayshaw , Richard A. Price , J. Harvey Turner. Phase II study of radiopeptide Lutetium-177-octreotate and Capecitabine therapy of progressive disseminated neuroendocrine tumours. Eur J Nucl Med Mol Imaging, under review
Public notes

Contacts
Principal investigator
Name 31198 0
Address 31198 0
Country 31198 0
Phone 31198 0
Fax 31198 0
Email 31198 0
Contact person for public queries
Name 14445 0
Ms. Jenny Lavin
Address 14445 0
Department of Nuclear Medicine
Fremantle Hospital
Alma Street
Fremantle WA 6160
Country 14445 0
Australia
Phone 14445 0
61 08 9431 2888
Fax 14445 0
61 08 9431 2889
Email 14445 0
[email protected]
Contact person for scientific queries
Name 5373 0
Professor J. Harvey Turner
Address 5373 0
Department of Nuclear Medicine
Fremantle Hospital
Alma Street
Fremantle WA 6160
Country 5373 0
Australia
Phone 5373 0
61 08 9431 2888
Fax 5373 0
61 08 9431 2889
Email 5373 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbasePancreatic neuroendocrine tumor control: Durable objective response to combination 177Lu-octreotate-capecitabine-temozolomide radiopeptide chemotherapy.2016https://dx.doi.org/10.1159/000434723
EmbaseTheranostic Outcomes in Clinical Practice of Oncology: What, so What, Now What? What's More.2019https://dx.doi.org/10.1089/cbr.2019.29006.jht
N.B. These documents automatically identified may not have been verified by the study sponsor.