A Randomised Phase II Study Comparing Capecitabine Plus Streptozocin With or Without Cisplatin Chemotherapy as Treatment for Unresectable or Metastatic Neuroendocrine Tumors
18 Years
N/A
Both
Gastrointestinal Carcinoid Tumor, Islet Cell Tumor
Trial Information
A Randomised Phase II Study Comparing Capecitabine Plus Streptozocin With or Without Cisplatin Chemotherapy as Treatment for 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.
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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Primary Purpose: Treatment
Outcome Measure:
Objective response rate
Principal Investigator
Pippa Corrie, PhD, FRCP
Investigator Affiliation:
Cambridge University Hospitals NHS Foundation Trust
Authority:
Unspecified
Study ID:
CDR0000582315
NCT ID:
NCT00602082
Start Date:
August 2005
Completion Date:
Related Keywords:
- Gastrointestinal Carcinoid Tumor
- Islet Cell Tumor
- 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
- Carcinoid Tumor
- Neuroendocrine Tumors
- Malignant Carcinoid Syndrome
- Gastrointestinal Neoplasms
- Adenoma, Islet Cell
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