Capecitabine And Streptozocin With Or Without Cisplatin In Treating Patients With Unresectable Or Metastatic Neuroendocrine Tumors

Study Overview

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

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.

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.

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

CRCA-CCTC-NET-01
CDR0000582315 (REGISTRY Identifier) (REGISTRY: PDQ (Physician Data Query))
EUDRACT-2004-005202-71
EU-207102
ISRCTN35124268

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2008-01-25	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2013-08-06
First Submitted that Met QC Criteria 2008-01-25	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ESTIMATED) 2013-08-07
First Posted (ESTIMATED) 2008-01-28	Results First Posted N/A	Last Verified 2009-06

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Randomized

Interventional Model:
N/A

Masking:
N/A

Arms and Interventions

Participant Group/Arm	Intervention/Treatment

Primary Outcome Measures	Measure Description	Time Frame
Objective response rate

Secondary Outcome Measures	Measure Description	Time Frame
Overall response rate
Functional response
Toxicity
Progression-free survival
Overall survival
Molecular markers predictive of response to chemotherapy
Quality of life

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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)

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

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

: Pippa Corrie, PhD, FRCP, Cambridge University Hospitals NHS Foundation Trust

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

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Clinical Trial Record