Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Capecitabine and Streptozocin With or Without Cisplatin in Treating Patients With Unresectable or Metastatic Neuroendocrine Tumors

Basic Trial Information

Objectives

Primary

1. To determine the objective response rate in patients with neuroendocrine tumors treated with capecitabine and streptozocin with or without cisplatin.

Secondary

1. To determine the overall response rate, including both objective and biochemical responses, to these regimens.
2. To determine the functional response to these regimens.
3. To determine the toxicity of these regimens.
4. To identify the optimal drug doses in each regimen to be recommended for a subsequent phase III trial.
5. To determine the progression-free and overall survival of patients receiving these regimens.
6. To determine the quality of life of these patients.
7. To determine molecular markers predictive of response to chemotherapy.

Entry Criteria

Disease Characteristics:

• Histologically confirmed unresectable, advanced, and/or metastatic disease meeting one of the following types:
  • Gastroentero-neuroendocrine tumor of the foregut
  • Pancreatic neuroendocrine tumor
  • Neuroendocrine tumor of unknown primary

• Measurable disease, defined as at least 1 lesion that can be accurately measured in at least 1 dimension (the longest diameter) ≥ 20 mm by conventional CT scanning or ≥ 10 mm by spiral CT scan or MRI

• No bronchial neuroendocrine tumors (NETs) or other NETs where the primary site is situated in organs above the diaphragm (e.g., laryngeal and pharyngeal NETs)

Prior/Concurrent Therapy:

• At least 3 weeks since prior interferon therapy
• No prior systemic chemotherapy or chemotherapy administered as part of a chemo-embolization regimen, or for this condition
• No receptor-targeted radiolabeled therapy within the past 6 months
• No investigational agent within the past 4 weeks
• Prior and concurrent somatostatin analogues allowed provided symptoms are no longer controlled by this treatment or there is documented measurable disease progression on serial CT scans performed up to 6 months apart
• No palliative radiotherapy involving lesions used to measure disease
  • Palliative radiotherapy to regions not involved in measurement of disease allowed
• No other concurrent chemotherapy for this condition

Patient Characteristics:

• ECOG performance status 0-2
• Life expectancy ≥ 12 weeks
• Hemoglobin ≥ 10 g/dL
• Platelet count ≥ 100,000/mm³
• WBC ≥ 3,000/mm³
• ANC ≥ 1,500/mm³
• Bilirubin ≤ 2 times upper limit of normal (ULN)
• Alkaline phosphatase ≤ 5 times ULN
• AST and ALT ≤ 5 times ULN
• GFR ≥ 60 mL/min
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 3 months after completion of study therapy
• No other serious or uncontrolled illness that would preclude study participation
• No medical or psychiatric condition that would influence the ability to provide consent

Expected Enrollment

Outcomes

Objective response rate

Overall response rate
Functional response
Toxicity
Progression-free survival
Overall survival
Molecular markers predictive of response to chemotherapy
Quality of life

Outline

This is a multicenter study. Patients are stratified according to site of origin (known vs unknown primary site), prior antitumor treatment, tumor function (functional vs nonfunctional), and study center. Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive streptozocin IV over 2 hours on day 1 and oral capecitabine twice daily on days 1-21.

• Arm II: Patients receive cisplatin IV over 2 hours on day 1 and streptozocin and capecitabine as in arm I.

In both treatment arms, treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Patients complete the EORTC QLQC30 questionnaire and EORTC QLQ-GI.NET21 module for quality-of-life assessment at baseline, every 9 weeks during treatment, and at 12 weeks post-treatment.

Tumor tissue is obtained at baseline and assessed for Ki67 and mitotic index. Novel tissue-specific transcription factors (e.g., CDX2) are also assessed. Blood samples are collected at baseline and 9 weeks and examined by DNA, RNA, and proteomic analysis.

After completion of study therapy, patients are followed every 12 weeks.

Trial Contact Information

Trial Lead Organizations

Addenbrooke's Hospital

Pippa Corrie, PhD, FRCP, Protocol co-chair		Ph: 44-1223-274-401 Email: pippa.corrie@addenbrookes.nhs.uk
Tim Meyer, MD, BSc, MRCP, PhD, Protocol co-chair		Ph: 44-207-679-6731

United Kingdom
England
	Basildon
	Basildon University Hospital
		Contact Person	Ph:  44-1702-435-555
	Cambridge
	Addenbrooke's Hospital
		Contact Person	Ph:  44-1223-245-151
	Leeds
	Cookridge Hospital
		Contact Person	Ph:  44-113-267-3411
	Leicester
	Leicester Royal Infirmary
		Contact Person	Ph:  44-116-254-1414
	Liverpool
	Aintree University Hospital
		Research Nurse	Ph:  44-151-529-5873
	London
	St. Thomas' Hospital
		Contact Person	Ph:  44-207-188-7188
	UCL Cancer Institute
		Contact Person	Ph:  44-207-794-2500
	Maidstone
	Mid Kent Oncology Centre at Maidstone Hospital
		Contact Person	Ph:  44-1622-729-000
	Manchester
	Christie Hospital
		Contact Person	Ph:  44-161-4468-8102
	Merseyside
	Clatterbridge Centre for Oncology
		Contact Person	Ph:  44-151-334-1155
	Newcastle-Upon-Tyne
	Northern Centre for Cancer Treatment at Newcastle General Hospital
		Contact Person	Ph:  44-191-233-6161
	Oxford
	Oxford Radcliffe Hospital
		Research Nurse	Ph:  44-186-522-6173
	Sutton
	Royal Marsden - Surrey
		Contact Person	Ph:  44-208-642-6044
	Westcliff-On-Sea
	Southend University Hospital NHS Foundation Trust
		Contact Person	Ph:  44-1702-435-555
Scotland
	Edinburgh
	Edinburgh Cancer Centre at Western General Hospital
		Contact Person	Ph:  44-131-537-1000
	Glasgow
	Beatson West of Scotland Cancer Centre
		Contact Person	Ph:  44-141-301-7057
Wales
	Cardiff
	Velindre Cancer Center at Velindre Hospital
		Contact Person	Ph:  44-29-2061-5888

Registry Information
Official Title		A randomised phase II study comparing capecitabine plus streptozocin with or without cisplatin chemotherapy as treatment for unresectable or metastatic neuroendocrine tumors
Trial Start Date		2005-08-23
Trial Completion Date		2009-12-31 (estimated)
Registered in ClinicalTrials.gov		NCT00602082
Date Submitted to PDQ		2008-01-24
Information Last Verified		2009-06-14

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