An Open Label, Single-Centre, Pilot Study of Everolimus With EBRT for the Treatment of mNET Liver Metastasis

Official Title

An Open Label, Single-Centre, Pilot Study for Radiosensitization of Everolimus With External Beam Radiation Therapy for the Treatment of Metastatic Neuroendocrine Liver Metastasis

Summary:

Approximately 50% of patients with neuroendocrine cancers present with metastasis, a vast majority to the liver. In such patients, one treatment option for liver-directed therapy is surgical resection. However, a significant proportion of patients are not eligible for resection because of patient factors (age, comorbidities) or tumour-related factors. There have been scant data on the utility of EBRT (external-beam radiation therapy) and SABR (stereotactic ablative radiation therapy) for metastatic neuroendocrine tumours of the liver. This study will measure the effects of concurrent everolimus with external-beam radiation therapy to the liver for metastatic neuroendocrine New methods of tumour assessment are needed in NETs. Three new techniques are being developed at the Sunnybrook Research Institute to assess tumour response to treatment: (1) contrast enhanced ultrasound; (2) perfusion CT; and (3) perfusion MRI. These methods are devised to measure tumour perfusion and blood flow as response indicators and can measure cell death non-invasively. 1. Concurrent everolimus given with external-beam radiation therapy to the liver for metastatic neuroendocrine tumours of the liver will enhance the efficacy of radiation therapy and add little, if any, toxicity 2. New radiological measures of CEUS and DCE-CT are effective measure to delineate tumour response in NETs.

Trial Description

Primary Outcome:

  • The tolerability and efficacy of Everolimus concurrent with external-beam radiation therapy will be examined
Secondary Outcome:
  • The response rate (as measured by RECIST version 1.1 criteria) of combined treatment with Everolimus and radiation to metastatic liver lesions in neuroendocrine cancers will be examined
  • The association between tumour perfusion and blood flow in vivo as measured by dynamic contrast-enhanced (DCE)-CT, CEUS, with clinical safety and efficacy outcomes will be preliminary explored
  • The effects of tumour perfusion and blood flow (on liver metastasis) as measured by DCE-MRI, DCE-CT and CEUS at baseline, during Everolimus but prior to SBRT, and post-SBRT in patients with neuroendocrine cancer metastatic to liver will be explored
  • The biochemical response (Urinary 5HIAA and Chromogranin A) of combined treatment with Everolimus and radiation to metastatic liver lesions in neuroendocrine cancers will be examined
This is an open label, single-centre, pilot study for Radiosensitization of Everolimus with external beam radiation therapy to the liver for metastatic neuroendocrine tumours The study will have 2 safety run-in dose levels: 2.5mg and 5mg Everolimus PO daily. Two patients will be enrolled into the 2.5mg dose level and 2 patients enrolled into the 5mg dose level. However, only one patient can start the safety run-in doses at a time. For the safety run-in dose levels, if no serious adverse events related to Everolimus occur within 30 days of the first dose of radiation therapy (in combination with Everolimus) in one patient, then the next patient can start study drug. The same criteria applies for the first 4 patients (2 patients on 2.5mg PO daily and 2 patients on 5 mg PO daily). If no serious adverse events related to Everolimus occur in the fourth patient at 5mg PO daily within 30 days of the first dose of radiation therapy (in combination with Everolimus), more than one patient can then be enrolled at one time at the target dose of 7.5mg PO daily. Ten patients will be enrolled at 7.5mg PO daily. For all patients, Everolimus starts 30 days prior to radiation and continues throughout radiation and for 14 days post radiation. Patients will receive Everolimus for 14 days post treatment only; as this pilot is designed to assess the combined effect of radiation and Everolimus. All patients will receive external-beam radiation therapy (30Gy in 10 fractions) or SBRT (up to 60Gy in 3-5 fractions given on alternating weekdays over 1-2 weeks). The decision to treat with either external-beam radiation therapy or SBRT will be based on whether the lesions are amenable to SBRT (preferred treatment), which is determined by the size of the target lesion, liver sparing and organs-at-risk dose constraints. The prescription dose of external-beam radiation therapy and SBRT will similarly be determined by these factors.

View this trial on ClinicalTrials.gov

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