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Clinical Study

A phase 2 trial of sunitinib in patients with progressive paraganglioma or pheochromocytoma: the SNIPP trial

Abstract

Background

Pheochromocytoma (PCC) and paraganglioma (PGL) are uncommon neoplasms with high morbidity in advanced stages. Effective systemic treatments are limited.

Methods

A multisite phase 2 trial evaluated sunitinib in patients with progressive PCC/PGL. Patients received 50 mg orally for 4–6 weeks.

Results

Between May 2009 and May 2016, 25 patients were enroled. The median age was 50 years and 56% were male. Three patients (12%) received prior chemotherapy and 16 (64%) prior surgery. The DCR was 83% (95% CI: 61–95%) and median PFS 13.4 (95% CI: 5.3–24.6) months. Of 23 evaluable patients, 3 (13%) with germline mutations (SDHA, SDHB, RET) achieved a PR. The patient with mutated RET and MEN2A remains on treatment after 64 cycles. The median time on treatment was 12.4 (1–88.0) months. Grade 3 or 4 toxicities were as expected and manageable; fatigue (16%) and thrombocytopenia (16%) were most common. One patient with grade 3 hypertension and 2 with grade 3 cardiac events discontinued treatment.

Conclusion

Although the primary endpoint of disease control was met, the overall response rate of sunitinib was low in unselected patients with progressive PCC/PGL. Patients with germline variants in RET or in the subunits of SDH may derive greatest benefit.

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Author information

G.O.K.: Patient materials, data collection, manuscript writing, statistical analysis SE. Patient materials, data collection, manuscript writing, statistical analysis A.J.: Study design, protocol development, patient materials, manuscript writing I.B.: patient materials, manuscript writing R.L.A.: Study design, protocol development, patient materials, manuscript writing H.O.: patient materials, manuscript writing M.K.: patient materials, manuscript writing D.R.: patient materials, manuscript writing S.C.: patient materials, manuscript writing L.W.: statistical analyses, manuscript writing K.B.: data collection, manuscript writing A.H.: Patient materials, manuscript writing S.A.: Patient materials, protocol development, manuscript writing J.K.: Study design, protocol development, patient materials, manuscript writing.

Correspondence to Jennifer J. Knox.

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Competing interests

The authors declare no competing interests.

Ethics approval and consent

This study was approved by the University Health Network (UHN) Research Ethics Board (REB) and submitted at each participating site. REB protocol number 08-0108. All patients provided informed consent as per study protocol. This consent included patient consent to collect clinical, demographic, genetic and outcome data for study publication. This study was conducted in accordance with the Declaration of Helsinki.

Data availability

This study is available withinthis publication and in the supplementary material. Further patient data can be requested from the corresponding author.

Note

This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution 4.0 International (CC BY 4.0).

Funding

This study was funded as part of an Investigator Initiated Trial from Pfizer Canada. Dr Jennifer Knox, the Principal Investigator was the study sponsor.

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