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

This study has been completed.
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00602082
First received: January 25, 2008
Last updated: August 6, 2013
Last verified: June 2009
  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 2

Study Type: Interventional
Study Design: Allocation: Randomized
Primary Purpose: Treatment
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:


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
Study Completion Date: December 2009
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United Kingdom
Basildon University Hospital
Basildon, England, United Kingdom, SS16 5NL
Addenbrooke's Hospital
Cambridge, England, United Kingdom, CB2 2QQ
Cookridge Hospital
Leeds, England, United Kingdom, LS16 6QB
Leicester Royal Infirmary
Leicester, England, United Kingdom, LE1 5WW
Aintree University Hospital
Liverpool, England, United Kingdom, L9 7AL
St. Thomas' Hospital
London, England, United Kingdom, SE1 7EH
UCL Cancer Institute
London, England, United Kingdom, NW3 2QG
Mid Kent Oncology Centre at Maidstone Hospital
Maidstone, England, United Kingdom, ME16 9QQ
Christie Hospital
Manchester, England, United Kingdom, M20 4BX
Clatterbridge Centre for Oncology
Merseyside, England, United Kingdom, CH63 4JY
Northern Centre for Cancer Treatment at Newcastle General Hospital
Newcastle-Upon-Tyne, England, United Kingdom, NE4 6BE
Oxford Radcliffe Hospital
Oxford, England, United Kingdom, 0X3 9DU
Royal Marsden - Surrey
Sutton, England, United Kingdom, SM2 5PT
Southend University Hospital NHS Foundation Trust
Westcliff-On-Sea, England, United Kingdom, SS0 0RY
Edinburgh Cancer Centre at Western General Hospital
Edinburgh, Scotland, United Kingdom, EH4 2XU
Beatson West of Scotland Cancer Centre
Glasgow, Scotland, United Kingdom, G12 0YN
Velindre Cancer Center at Velindre Hospital
Cardiff, Wales, United Kingdom, CF14 2TL
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 University College London (UCL) Cancer Institute
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00602082     History of Changes
Other Study ID Numbers: CRCA-CCTC-NET-01, CDR0000582315, EUDRACT-2004-005202-71, EU-207102, ISRCTN35124268
Study First Received: January 25, 2008
Last Updated: August 6, 2013
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:
Carcinoid Tumor
Neuroendocrine Tumors
Malignant Carcinoid Syndrome
Gastrointestinal Neoplasms
Adenoma, Islet Cell
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Adenoma
Pancreatic Neoplasms
Endocrine Gland Neoplasms
Pancreatic Diseases
Endocrine System Diseases
Capecitabine
Cisplatin
Streptozocin
Fluorouracil
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on July 20, 2014