Clinical trial NCT00602082: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Gastrointestinal Carcinoid Tumor
Islet Cell Tumor
Keywords: 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
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2008-01-28
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Objective response rate
Secondary outcomes:
measure: Overall response rate
measure: Functional response
measure: Toxicity
measure: Progression-free survival
measure: Overall survival
measure: Molecular markers predictive of response to chemotherapy
measure: Quality of life
Other outcomes:
Locations:
city: Basildon
country: United Kingdom
facility: Basildon University Hospital
state: England
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
state: England
city: Leeds
country: United Kingdom
facility: Cookridge Hospital
state: England
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
state: England
city: Liverpool
country: United Kingdom
facility: Aintree University Hospital
state: England
city: London
country: United Kingdom
facility: UCL Cancer Institute
state: England
city: London
country: United Kingdom
facility: St. Thomas' Hospital
state: England
city: Maidstone
country: United Kingdom
facility: Mid Kent Oncology Centre at Maidstone Hospital
state: England
city: Manchester
country: United Kingdom
facility: Christie Hospital
state: England
city: Merseyside
country: United Kingdom
facility: Clatterbridge Centre for Oncology
state: England
city: Newcastle-Upon-Tyne
country: United Kingdom
facility: Northern Centre for Cancer Treatment at Newcastle General Hospital
state: England
city: Oxford
country: United Kingdom
facility: Oxford Radcliffe Hospital
state: England
city: Sutton
country: United Kingdom
facility: Royal Marsden - Surrey
state: England
city: Westcliff-On-Sea
country: United Kingdom
facility: Southend University Hospital NHS Foundation Trust
state: England
city: Edinburgh
country: United Kingdom
facility: Edinburgh Cancer Centre at Western General Hospital
state: Scotland
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
state: Scotland
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Center at Velindre Hospital
state: Wales
Study officials:
affiliation: Cambridge University Hospitals NHS Foundation Trust
name: Pippa Corrie, PhD, FRCP
affiliation: University College London (UCL) Cancer Institute
name: Tim Meyer, MD, BSc, MRCP, PhD
References: