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

NCT ID: NCT00602082

Last Updated: 2013-08-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

84 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-08-31

Study Completion Date

2009-12-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Gastrointestinal Carcinoid Tumor Islet Cell Tumor

Keywords

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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

Study Design

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Allocation Method

RANDOMIZED

Primary Study Purpose

TREATMENT

Interventions

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capecitabine

Intervention Type DRUG

cisplatin

Intervention Type DRUG

streptozocin

Intervention Type DRUG

DNA analysis

Intervention Type GENETIC

RNA analysis

Intervention Type GENETIC

protein analysis

Intervention Type GENETIC

proteomic profiling

Intervention Type GENETIC

laboratory biomarker analysis

Intervention Type OTHER

Eligibility Criteria

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Inclusion 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Cambridge University Hospitals NHS Foundation Trust

OTHER

Sponsor Role lead

Principal Investigators

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Pippa Corrie, PhD, FRCP

Role:

Cambridge University Hospitals NHS Foundation Trust

Tim Meyer, MD, BSc, MRCP, PhD

Role:

University College London (UCL) Cancer Institute

Locations

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Basildon University Hospital

Basildon, England, United Kingdom

Site Status

Addenbrooke's Hospital

Cambridge, England, United Kingdom

Site Status

Cookridge Hospital

Leeds, England, United Kingdom

Site Status

Leicester Royal Infirmary

Leicester, England, United Kingdom

Site Status

Aintree University Hospital

Liverpool, England, United Kingdom

Site Status

UCL Cancer Institute

London, England, United Kingdom

Site Status

St. Thomas' Hospital

London, England, United Kingdom

Site Status

Mid Kent Oncology Centre at Maidstone Hospital

Maidstone, England, United Kingdom

Site Status

Christie Hospital

Manchester, England, United Kingdom

Site Status

Clatterbridge Centre for Oncology

Merseyside, England, United Kingdom

Site Status

Northern Centre for Cancer Treatment at Newcastle General Hospital

Newcastle upon Tyne, England, United Kingdom

Site Status

Oxford Radcliffe Hospital

Oxford, England, United Kingdom

Site Status

Royal Marsden - Surrey

Sutton, England, United Kingdom

Site Status

Southend University Hospital NHS Foundation Trust

Westcliff-on-Sea, England, United Kingdom

Site Status

Edinburgh Cancer Centre at Western General Hospital

Edinburgh, Scotland, United Kingdom

Site Status

Beatson West of Scotland Cancer Centre

Glasgow, Scotland, United Kingdom

Site Status

Velindre Cancer Center at Velindre Hospital

Cardiff, Wales, United Kingdom

Site Status

Countries

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United States United Kingdom

Other Identifiers

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CDR0000582315

Identifier Type: REGISTRY

Identifier Source: secondary_id

EUDRACT-2004-005202-71

Identifier Type: -

Identifier Source: secondary_id

EU-207102

Identifier Type: -

Identifier Source: secondary_id

ISRCTN35124268

Identifier Type: -

Identifier Source: secondary_id

CRCA-CCTC-NET-01

Identifier Type: -

Identifier Source: org_study_id