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

Study Overview
=================
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.

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

Conditions
-----------------
Gastrointestinal Carcinoid Tumor, Islet Cell Tumor

Intervention / Treatment
-----------------
* Drug: capecitabine
* Drug: cisplatin
* Drug: streptozocin
* Genetic: DNA analysis
* Genetic: RNA analysis
* Genetic: protein analysis
* Genetic: proteomic profiling
* Other: laboratory biomarker analysis


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: capecitabine|nan|
|Drug: cisplatin|nan|
|Drug: streptozocin|nan|
|Genetic: DNA analysis|nan|
|Genetic: RNA analysis|nan|
|Genetic: protein analysis|nan|
|Genetic: proteomic profiling|nan|
|Other: laboratory biomarker analysis|nan|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate |  |  | 
| Functional response |  |  | 
| Toxicity |  |  | 
| Progression-free survival |  |  | 
| Overall survival |  |  | 
| Molecular markers predictive of response to chemotherapy |  |  | 
| Quality of life |  |  | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
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