A Randomised Phase II Study Comparing Capecitabine Plus Streptozocin With or Without Cisplatin Chemotherapy as Treatment for Unresectable or Metastatic Neuroendocrine Tumors
- To determine the objective response rate in patients with neuroendocrine tumors treated
with capecitabine and streptozocin with or without cisplatin.
- 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
- 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
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.
Allocation: Randomized, Primary Purpose: Treatment
Objective response rate
Pippa Corrie, PhD, FRCP
Cambridge University Hospitals NHS Foundation Trust