DOTA-TOC in Metastasized Neuroendocrine Tumors

Phase II Study of [90Y-DOTA]-TOC and [177Lu-DOTA]-TOC in Metastasized Neuroendocrine Tumors

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.

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

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