Through this QUICK TRIAL, we propose to offer a new therapy to children with relapsed solid tumors.Previous work from our laboratory and from other investigators has established the expression of somatostatin receptors in neuroblastoma, medulloblastoma, the Ewing's sarcoma family of tumors and osteogenic sarcoma. These solid tumors of childhood are challenges to pediatric oncologists because they often present at advanced stages of disease and few treatment options are available for children whose disease relapses or progresses. We hypothesize that somatostatin receptors can be exploited as a therapeutic target in the subset of pediatric solid tumors that can be demonstrated to express somatostatin receptors.
The Specific Aims are: I. Conduct a Phase I trial to determine the maximum tolerated dose of 90Y-DOTA-tyr3-Octreotide in children with refractory neuroblastoma, medulloblastoma, and other somatostatin receptor positive tumors. Patients with progressive disease after completion of front line therapy will be screened using 1111n-DTPA-Octreotide scintigraphy. Children who have at least one somatostatin receptor positive lesion documented by histology (previous or current) and by scintigraphy will be eligible to receive 90Y-DOTA-tyr3-Octreotide. Dose escalation will be based on dosimetry measurements in kidney, the predicted organ of limiting toxicity. II. Estimate tumor dose and determine response to therapy (in the context of a Phase I trial).Tumor dosimetry will be estimated using co-registration of CT or MRI images of tumor and functional SPECT images of 111ln-DTPA-Octreotide uptake. Number of complete responses, partial responses, stable disease and tumor progressions will be compared with tumor dose within the limited number of patients/dose in this Phase I trial. III. Test if tumor dose correlates with somatostatin receptor type 2 (sst2) expression as measured by real time RT-PCR and immunohistochemistry. Patients will undergo biopsy of at least one co-registered lesion for histology and quantification of somatostatin receptor expression by Real-time RT-PCR using receptor specific primers and probes developed in our laboratory. Somatostatin receptor protein will be examined by semiquantitative immunohistochemistry using specific sst2 antisera generated in our laboratory. The sst2 expression will be compared with tumor dosimetry and tumor response in order to determine if Real-time RT-PCR analysis of tumor receptor expression can predict response.
| Menda, Yusuf; O'Dorisio, M Sue; Kao, Simon et al. (2010) Phase I trial of 90Y-DOTATOC therapy in children and young adults with refractory solid tumors that express somatostatin receptors. J Nucl Med 51:1524-31 |
| Lal, Geeta; Padmanabha, Lakshmi; Nicholson, Rachael et al. (2008) ECM1 expression in thyroid tumors--a comparison of real-time RT-PCR and IHC. J Surg Res 149:62-8 |
| Lal, Geeta; Padmanabha, Lakshmi; Smith, Brian J et al. (2006) RIZ1 is epigenetically inactivated by promoter hypermethylation in thyroid carcinoma. Cancer 107:2752-9 |
