An Open Label, Single-Centre, Pilot Study of Everolimus With EBRT for the Treatment of mNET Liver Metastasis (EBRT)
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|ClinicalTrials.gov Identifier: NCT02205515|
Recruitment Status : Recruiting
First Posted : July 31, 2014
Last Update Posted : July 26, 2016
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 tumor-related factors.
There have been scant data on the utility of EBRT (external-beam radiotherapy) and SABR (stereotactic ablative radiotherapy) for metastatic neuroendocrine tumors of the liver. This study will measure the effects of concurrent everolimus with external-beam radiotherapy to the liver for metastatic neuroendocrine New methods of tumor 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.
- Concurrent everolimus given with external-beam radiotherapy to the liver for metastatic neuroendocrine tumors of the liver will enhance the efficacy of radiotherapy and add little, if any, toxicity
- New radiological measures of CEUS and DCE-CT are effective measure to delineate tumor response in NETs.
|Condition or disease||Intervention/treatment||Phase|
|Carcinoma, Neuroendocrine||Drug: Everolimus||Phase 1 Phase 2|
This is an open label, single-centre, pilot study for Radiosensitization of Everolimus with external beam radiotherapy to the liver for metastatic neuroendocrine tumors 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 radiotherapy (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 radiotherapy 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 radiotherapy and SBRT will similarly be determined by these factors.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||14 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||An Open Label, Single-Centre, Pilot Study for Radiosensitization of Everolimus With External Beam Radiotherapy for the Treatment of Metastatic Neuroendocrine Liver Metastasis|
|Study Start Date :||March 2016|
|Estimated Primary Completion Date :||March 2018|
|Estimated Study Completion Date :||March 2020|
SBRT or EBRT
Everolimus is a novel derivative of rapamycin.
Other Name: Afinitor
- The tolerability and efficacy of Everolimus concurrent with external-beam radiotherapy will be examined [ Time Frame: Through study completion an average of 1 year ]
- 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 [ Time Frame: Screening, every 12weeks during the study until off-treatment due to progression ]
- The association between tumor 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 [ Time Frame: During the duration of the study ]
- The effects of tumor 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 [ Time Frame: Screening, Day 26-28, and 7 days follow-up after last RT ]
- 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 [ Time Frame: Screening, Day 26-28, and 7 days follow-up after last RT, 30 & 90 days after completing radiotherapy and at progression. 5HIAA to be also done as clinically indicated ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02205515
|Contact: Simron Singh, MD||416-480-5000 ext email@example.com|
|Odette Cancer Centre, Sunnybrook Health Science Centre||Recruiting|
|Toronto, Ontario, Canada, M4N 3M5|
|Principal Investigator: Simron Singh, md|
|Principal Investigator:||Simron Singh, MD||Odette Cancer Centre, Sunnybrook HSC|