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

Gastrointestinal Carcinoid Tumor Clinical Trial

Official title:

A Randomised Phase II Study Comparing Capecitabine Plus Streptozocin With or Without Cisplatin Chemotherapy as Treatment for Unresectable or Metastatic Neuroendocrine Tumors

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00602082
• Other study ID #: CRCA-CCTC-NET-01
• Secondary ID: CDR0000582315EUD
• Status: Completed
• Phase: Phase 2
• First received: January 25, 2008
• Last updated: August 6, 2013
• Start date: August 2005
• Est. completion date: December 2009

Study information

• Verified date: June 2009
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: Unspecified
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 84
• Est. completion date: December 2009
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoid Tumor
• Gastrointestinal Carcinoid Tumor
• Gastrointestinal Neoplasms
• Islet Cell Tumor
• Malignant Carcinoid Syndrome
• Neoplasms
• Neuroendocrine Tumors

Intervention

Drug:
• capecitabine

• cisplatin

• streptozocin

Genetic:
• DNA analysis

• RNA analysis

• protein analysis

• proteomic profiling

Other:
• laboratory biomarker analysis

Locations

Country	Name	City	State
United Kingdom	Basildon University Hospital	Basildon	England
United Kingdom	Addenbrooke's Hospital	Cambridge	England
United Kingdom	Velindre Cancer Center at Velindre Hospital	Cardiff	Wales
United Kingdom	Edinburgh Cancer Centre at Western General Hospital	Edinburgh	Scotland
United Kingdom	Beatson West of Scotland Cancer Centre	Glasgow	Scotland
United Kingdom	Cookridge Hospital	Leeds	England
United Kingdom	Leicester Royal Infirmary	Leicester	England
United Kingdom	Aintree University Hospital	Liverpool	England
United Kingdom	St. Thomas' Hospital	London	England
United Kingdom	UCL Cancer Institute	London	England
United Kingdom	Mid Kent Oncology Centre at Maidstone Hospital	Maidstone	England
United Kingdom	Christie Hospital	Manchester	England
United Kingdom	Clatterbridge Centre for Oncology	Merseyside	England
United Kingdom	Northern Centre for Cancer Treatment at Newcastle General Hospital	Newcastle-Upon-Tyne	England
United Kingdom	Oxford Radcliffe Hospital	Oxford	England
United Kingdom	Royal Marsden - Surrey	Sutton	England
United Kingdom	Southend University Hospital NHS Foundation Trust	Westcliff-On-Sea	England

Sponsors (1)

Lead Sponsor	Collaborator
Cambridge University Hospitals NHS Foundation Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective response rate
Secondary	Overall response rate
Secondary	Functional response
Secondary	Toxicity
Secondary	Progression-free survival
Secondary	Overall survival
Secondary	Molecular markers predictive of response to chemotherapy
Secondary	Quality of life