Capecitabine and Streptozocin With or Without Cisplatin in Treating Patients With Unresectable or Metastatic Neuroendocrine Tumors - Full Text View

Sponsor:	Cambridge University Hospitals NHS Foundation Trust
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00602082

Purpose

RATIONALE: Drugs used in chemotherapy, such as capecitabine, streptozocin, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether giving capecitabine together with streptozocin is more effective with or without cisplatin in treating neuroendocrine tumors.

PURPOSE: This randomized phase II trial is studying giving capecitabine together with streptozocin to see how well it works compared with or without cisplatin in treating patients with unresectable or metastatic neuroendocrine tumors.

Condition	Intervention	Phase
Gastrointestinal Carcinoid Tumor Islet Cell Tumor	Drug: capecitabine Drug: cisplatin Drug: streptozocin Genetic: DNA analysis Genetic: RNA analysis Genetic: protein analysis Genetic: proteomic profiling Other: laboratory biomarker analysis	Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized
Official Title:	A Randomised Phase II Study Comparing Capecitabine Plus Streptozocin With or Without Cisplatin Chemotherapy as Treatment for Unresectable or Metastatic Neuroendocrine Tumors

Resource links provided by NLM:

MedlinePlus related topics: Cancer Carcinoid Tumors

Drug Information available for: Cisplatin Streptozocin Capecitabine

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Objective response rate

Secondary Outcome Measures:

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

Estimated Enrollment:	84
Study Start Date:	August 2005
Estimated Primary Completion Date:	December 2009 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

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

Secondary

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

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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)

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

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00602082

Locations

United Kingdom, England
Addenbrooke's Hospital	Recruiting
Cambridge, England, United Kingdom, CB2 2QQ
Contact: Contact Person 44-1223-245-151
Aintree University Hospital	Recruiting
Liverpool, England, United Kingdom, L9 7AL
Contact: Research Nurse 44-151-529-5873
Basildon University Hospital	Recruiting
Basildon, England, United Kingdom, SS16 5NL
Contact: Contact Person 44-1702-435-555
Christie Hospital	Recruiting
Manchester, England, United Kingdom, M20 4BX
Contact: Contact Person 44-161-4468-8102
Mid Kent Oncology Centre at Maidstone Hospital	Recruiting
Maidstone, England, United Kingdom, ME16 9QQ
Contact: Contact Person 44-1622-729-000
Cookridge Hospital	Recruiting
Leeds, England, United Kingdom, LS16 6QB
Contact: Contact Person 44-113-267-3411
Leicester Royal Infirmary	Recruiting
Leicester, England, United Kingdom, LE1 5WW
Contact: Contact Person 44-116-254-1414
Clatterbridge Centre for Oncology	Recruiting
Merseyside, England, United Kingdom, CH63 4JY
Contact: Contact Person 44-151-334-1155
Northern Centre for Cancer Treatment at Newcastle General Hospital	Recruiting
Newcastle-Upon-Tyne, England, United Kingdom, NE4 6BE
Contact: Contact Person 44-191-233-6161
Oxford Radcliffe Hospital	Recruiting
Oxford, England, United Kingdom, 0X3 9DU
Contact: Research Nurse 44-186-522-6173
Royal Marsden - Surrey	Recruiting
Sutton, England, United Kingdom, SM2 5PT
Contact: Contact Person 44-208-642-6044
Southend University Hospital NHS Foundation Trust	Recruiting
Westcliff-On-Sea, England, United Kingdom, SS0 0RY
Contact: Contact Person 44-1702-435-555
St. Thomas' Hospital	Recruiting
London, England, United Kingdom, SE1 7EH
Contact: Contact Person 44-207-188-7188
UCL Cancer Institute	Recruiting
London, England, United Kingdom, NW3 2QG
Contact: Contact Person 44-207-794-2500
United Kingdom, Scotland
Beatson West of Scotland Cancer Centre	Recruiting
Glasgow, Scotland, United Kingdom, G12 0YN
Contact: Contact Person 44-141-301-7057
Edinburgh Cancer Centre at Western General Hospital	Recruiting
Edinburgh, Scotland, United Kingdom, EH4 2XU
Contact: Contact Person 44-131-537-1000
United Kingdom, Wales
Velindre Cancer Center at Velindre Hospital	Recruiting
Cardiff, Wales, United Kingdom, CF14 2TL
Contact: Contact Person 44-29-2061-5888

Sponsors and Collaborators

Cambridge University Hospitals NHS Foundation Trust

Investigators

Investigator:	Pippa Corrie, PhD, FRCP	Cambridge University Hospitals NHS Foundation Trust
Investigator:	Tim Meyer, MD, BSc, MRCP, PhD	UCL Cancer Institute

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000582315, CRCA-CCTC-NET-01, EUDRACT-2004-005202-71, EU-207102, ISRCTN35124268
Study First Received:	January 25, 2008
Last Updated:	July 15, 2009
ClinicalTrials.gov Identifier:	NCT00602082 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

pancreatic alpha cell adenoma
pancreatic alpha cell carcinoma
pancreatic beta islet cell adenoma
pancreatic beta islet cell carcinoma
pancreatic delta cell adenoma
pancreatic delta cell carcinoma
pancreatic G-cell adenoma
pancreatic G-cell carcinoma
gastrinoma

insulinoma
glucagonoma
pancreatic polypeptide tumor
somatostatinoma
metastatic gastrointestinal carcinoid tumor
recurrent gastrointestinal carcinoid tumor
regional gastrointestinal carcinoid tumor
islet cell carcinoma
recurrent islet cell carcinoma

Additional relevant MeSH terms:

Antimetabolites
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Gastrointestinal Diseases
Pancreatic Neoplasms
Physiological Effects of Drugs
Neoplasms, Nerve Tissue
Antibiotics, Antineoplastic
Neoplasms by Site
Cisplatin
Therapeutic Uses
Neoplasms, Germ Cell and Embryonal
Endocrine Gland Neoplasms
Capecitabine

Neoplasms by Histologic Type
Digestive System Neoplasms
Endocrine System Diseases
Adenoma, Islet Cell
Malignant Carcinoid Syndrome
Streptozocin
Pharmacologic Actions
Carcinoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms
Digestive System Diseases
Radiation-Sensitizing Agents
Gastrointestinal Neoplasms
Pancreatic Diseases

ClinicalTrials.gov processed this record on November 05, 2009