Clinical trial NCT00978211: DOTA-TOC in Metastasized Neuroendocrine Tumors
Official title: Phase II Study of [90Y-DOTA]-TOC and [177Lu-DOTA]-TOC in Metastasized Neuroendocrine Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Neuroendocrine Tumors
Keywords: DOTATOC
somatostatin
radiopeptide
Yttrium
Lutetium
neuroendocrine
cancer
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2009-09-16
Enrollment: 1499
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The investigators aim to explore the efficacy of \[90Y-DOTA\]-TOC and \[177LuDOTA\]-TOC therapy in advanced neuroendocrine cancer. Therefore, the investigators assess response, survival and long-term safety profile of systemic \[90Y-DOTA\]-TOC and \[177LuDOTA\]-TOC treatment in metastasized neuroendocrine cancer patients. Adverse events are assessed according to the criteria of the National Cancer Institute. Survival analyses are performed using multiple regression models.

Detailed description: Background: Systemic treatment with the 90Yttrium (90Y) labeled, tetraazacyclododecanetetraacetic acid (DOTA) modified somatostatin analog Tyr3-octreotide (TOC) was introduced in 1998 (Otte et al. Lancet 1998). \[90Y-DOTA\]-TOC is administered intravenously and binds to the somatostatin receptor subtype 2, located on the surface of the tumor cell, and exerts its cytotoxic effects by β-irradiation. The treatment has moderate acute hematologic and nephrologic toxicity and has developed into a promising therapeutic tool for tumors expressing its target receptor (Iten et al. Clin Cancer Res 2007, Iten et al. Cancer 2009).

Study Aim: To explore the efficacy of \[90Y-DOTA\]-TOC and \[177LuDOTA\]-TOC therapy in advanced neuroendocrine cancer.

Study Hypothesis: Response to DOTA-TOC is correlated with prolonged survival.

Study Type: Clinical phase II, single-center, open-label trial

Patients: 1500 patients

Eligibility criteria: Inclusion Criteria:

* histologically confirmed neuroendocrine cancer
* stage IVc disease by definition of the American Joint Committee on Cancer, i.e. occurrence of distant metastases
* visible tumor uptake in the pretherapeutic somatostatin receptor subtype 2 scintigraphy (111In-Octreoscan)

Exclusion Criteria:

* concurrent anti-tumor treatment
* secondary malignancies
* pregnancy
* breast-feeding
* incontinence
* severe concomitant illness including severe psychiatric disorders

Primary outcomes:
measure: Response
timeFrame: 3 months
Secondary outcomes:
measure: Toxicity
timeFrame: 3 months
measure: Survival
timeFrame: life-long
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: University Hospital
state: BS
Study officials:
affiliation: Institute of Nuclear Medicine; Inselspital Bern
name: Martin A Walter, MD, Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Otte A, Mueller-Brand J, Dellas S, Nitzsche EU, Herrmann R, Maecke HR. Yttrium-90-labelled somatostatin-analogue for cancer treatment. Lancet. 1998 Feb 7;351(9100):417-8. doi: 10.1016/s0140-6736(05)78355-0. No abstract available.
citation: Iten F, Muller B, Schindler C, Rochlitz C, Oertli D, Macke HR, Muller-Brand J, Walter MA. Response to [90Yttrium-DOTA]-TOC treatment is associated with long-term survival benefit in metastasized medullary thyroid cancer: a phase II clinical trial. Clin Cancer Res. 2007 Nov 15;13(22 Pt 1):6696-702. doi: 10.1158/1078-0432.CCR-07-0935.
citation: Iten F, Muller B, Schindler C, Rasch H, Rochlitz C, Oertli D, Maecke HR, Muller-Brand J, Walter MA. [(90)Yttrium-DOTA]-TOC response is associated with survival benefit in iodine-refractory thyroid cancer: long-term results of a phase 2 clinical trial. Cancer. 2009 May 15;115(10):2052-62. doi: 10.1002/cncr.24272.
citation: Marincek N, Jorg AC, Brunner P, Schindler C, Koller MT, Rochlitz C, Muller-Brand J, Maecke HR, Briel M, Walter MA. Somatostatin-based radiotherapy with [90Y-DOTA]-TOC in neuroendocrine tumors: long-term outcome of a phase I dose escalation study. J Transl Med. 2013 Jan 15;11:17. doi: 10.1186/1479-5876-11-17.