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

• ClinicalTrials.gov Identifier: NCT00602082
• Recruitment Status: Completed
• First Posted: January 28, 2008
• Last Update Posted: August 7, 2013
• Sponsor: Cambridge University Hospitals NHS Foundation Trust
• Information provided by: National Cancer Institute (NCI)

Tracking Information

• First Submitted Date: January 25, 2008
• First Posted Date: January 28, 2008
• Last Update Posted Date: August 7, 2013
• Study Start Date: August 2005
• Actual Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: January 25, 2008): Objective response rate
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 25, 2008)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Capecitabine and Streptozocin With or Without Cisplatin in Treating Patients With Unresectable or Metastatic Neuroendocrine Tumors
• Official Title: A Randomised Phase II Study Comparing Capecitabine Plus Streptozocin With or Without Cisplatin Chemotherapy as Treatment for Unresectable or Metastatic Neuroendocrine Tumors

Brief 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.

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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Primary Purpose: Treatment

Condition

• Gastrointestinal Carcinoid Tumor
• Islet Cell Tumor

Intervention

• Drug: capecitabine
• Drug: cisplatin
• Drug: streptozocin
• Genetic: DNA analysis
• Genetic: RNA analysis
• Genetic: protein analysis
• Genetic: proteomic profiling
• Other: laboratory biomarker analysis

• Study Arms: Not Provided
• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Estimated Enrollment (submitted: January 25, 2008): 84
• Original Enrollment: Same as current
• Actual Study Completion Date: December 2009
• Actual Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United Kingdom
• Removed Location Countries: United States

Administrative Information

• NCT Number: NCT00602082
• Other Study ID Numbers: CRCA-CCTC-NET-01; CDR0000582315 ( Registry Identifier: PDQ (Physician Data Query) ); EUDRACT-2004-005202-71; EU-207102; ISRCTN35124268
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Not Provided
• Original Responsible Party: Same as current
• Current Study Sponsor: Cambridge University Hospitals NHS Foundation Trust
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Investigator: Pippa Corrie, PhD, FRCP; Cambridge University Hospitals NHS Foundation Trust
• Investigator: Tim Meyer, MD, BSc, MRCP, PhD; University College London (UCL) Cancer Institute

• PRS Account: National Cancer Institute (NCI)
• Verification Date: June 2009