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Carcinoma, NeuroendocrinePhase 1/2EBRTNCT02205515

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

A Phase 1/2 study testing Everolimus in people with Carcinoma, Neuroendocrine, run by Sunnybrook Health Sciences Centre at 1 site in Canada.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Carcinoma, Neuroendocrine
What is being tested?
Everolimus
Could I receive a placebo?
No, everyone receives an active treatment
How many people
17 participants
Where
1 siteCanada
Study dates
Mar 2016to Oct 2021
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histological and/or cytological diagnosis of unresectable neuroendocrine tumor with liver metastases confirmed on imaging scans
  • Ki-67<55%
  • No prior Everolimus within 3 months prior to registration
  • No prior radiotherapy to the liver
  • 1-3 liver metastatic lesions confirmed on imaging scans
  • Size of target metastatic lesion is 6 cm or less
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  • At least 700 cc of liver uninvolved by tumor
  • Previous liver resection, systemic therapy or local ablation therapy (radiofrequency ablation, transarterial chemoemolization, radioemolization) is allowed.
  • Extrahepatic disease is allowed if maximum involved organs (including the liver) is 3 or less (i.e. oligometastases).
  • Child-Pugh's A liver function
  • Male or female: Age ≥ 18 years
  • Life expectancy > 6 months
  • ECOG PS ≤1
  • Laboratory Requirements - within 14 days prior to registration:
  • Hematology Absolute Neutrophils Count ≥ 1.5 x 109/L Platelets ≥ 100 x 109/L Hemoglobin ≥ 90 g/L Biochemistry Serum Bilirubin ≤ 1.5 x upper limit of normal Serum Creatinine ≤ 1.5 x upper limit of normal AST ≤ 3 x upper limit of normal ALT ≤ 3 x upper limit of normal INR ≤ 1.5 Fasting Serum Cholesterol ≤ 300 mg/dl or 7.75 mmol/L Fasting Triglycerides ≤ 2.5 x ULN Adequate Glucose Control Urinalysis Proteinuria ≤ grade 1 (by dipstick)
  • Before patient registration/randomization, written informed consent must be given according to local Institutional and/or University Human Experimentation Committee requirements. The patient must sign the consent form prior to randomization or registration.
  • Patients that have a positive HBV-DNA result at screening must agree to take prophylactic treatment for 1-2 weeks prior to beginning Everolimus treatment. See section 7.2 for further information on Viral Hepatitis management
  • Patients must be accessible for treatment and follow-up. Patients registered on this trial must be treated and followed at the participating centre. Investigators must assure themselves the patients registered on this trial will be available for complete documentation of the treatment, adverse events response assessment and follow-up.

Who cannot join

  • Major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to registration (i.e. patients must have recovered to less than or equal to grade 1 from any major surgery), or anticipation of need for major surgical procedure during or within 7 weeks after chemo-radiotherapy
  • Known to have clinical or radiological evidence of CNS metastases
  • Patients with hepatitis
  • Patients with neuroendocrine tumor of a pancreatic origin
  • Patients with a past or current history (within last 2 years) of other malignancies, except for the indication under this study and curatively treated basal and squamous skin cancer or in-situ cancer of the cervix. Prior treatment of localized prostate cancer is permitted if treatment was greater than 5 years ago and the patient currently has no biochemical evidence of recurrence.
  • Uncontrolled diabetes mellitus
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  • Active bleeding diathesis, or an oral anti-vitamin K medication (except low dose warfarin, LMWH, or acetylsalicylic acid or equivalent) as long as the INR is <1.5.
  • Patients with known history or present encephalopathy
  • Gross clinically detectable ascites
  • Any comorbidity or concomitant medication that would contraindicate treatment with Everolimus
  • Women of childbearing potential with a positive pregnancy test at baseline or lactating. Postmenopausal women must have been amenorrheic for at least 12 months to be considered of non-childbearing potential. Females patients must not be pregnant or become pregnant during this study and for 6 months after the last dose of Everolimus
  • Sexually active males and females (of childbearing potential) unwilling to practice contraception during the study. Patients of childbearing potential must be willing to use a reliable method of birth control. i.e.: double barrier method, oral contraceptive, implant, dermal contraception, long-term injectable contraceptive, intrauterine device or tubal ligation during the study.
  • Prior radiotherapy to the right upper quadrant of the liver
  • Contraindication to CT dye injection
  • Contraindication to MRI
  • Contraindication to CEUS dye injection
  • Body habitus and or tumor location not allowing for CEUS
  • Any other serious intercurrent illness such as cardiovascular disease, HIV or any neurological disease
  • Patients taking other approved or investigational drug/anticancer treatment (other than ongoing androgen ablation and oral prednisone which are permitted) during the study period, including chemotherapy, biological response modifiers, immunotherapy, surgery or radiotherapy.
  • Patients concurrently participating in another clinical trial
  • Patients unwilling to or unable to comply with the treatment plan
  • Patients who have metastatic liver lesions that are candidates for resection

Trial locations and contacts

1 site in 1 country.

Canada1 site

  • Odette Cancer Centre, Sunnybrook Health Science Centre

    Toronto, Ontario, M4N 3M5

Other trials in Canada

About this study

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

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.

  1. 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
  2. New radiological measures of CEUS and DCE-CT are effective measure to delineate tumor response in NETs.
Read the detailed description

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.

Being tested
Everolimus
Medical subject headings
Carcinoma, Neuroendocrine

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • EverolimusDrug

    Also called Afinitor

    Everolimus is a novel derivative of rapamycin.

Study groups in NCT02205515
Study groupRoleWhat they receive
RadiotherapyOtherSBRT or EBRT
Receives: Drug: Everolimus

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The tolerability and efficacy of Everolimus concurrent with external-beam radiotherapy will be examined

    Measured: Through study completion an average of 1 year

Secondary outcomes (4)

  1. 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

    Measured: Screening, every 12weeks during the study until off-treatment due to progression

  2. 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

    Measured: During the duration of the study

  3. 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

    Measured: Screening, Day 26-28, and 7 days follow-up after last RT

  4. 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

    Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Jul 2014 (estimated)
  2. Study startMar 2016
  3. Primary completionSep 2021
  4. Study completionOct 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
17 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02205515
Sponsor's protocol ID
File#13-907/OZM-057
Acronym
EBRT
Status last verified
Aug 2022
First submitted
25 Jun 2014
Last updated
19 Aug 2022
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Everolimus in people with Carcinoma, Neuroendocrine, run by Sunnybrook Health Sciences Centre at 1 site in Canada.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The tolerability and efficacy of Everolimus concurrent with external-beam radiotherapy will be examined (time frame: Through study completion an average of 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02205515.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Aug 2022.

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