Liver MetastasisPhase 1/2NCT00892424
Sorafenib-RT Treatment for Liver Metastasis (SLIM)
A Phase 1/2 study testing Sorafenib in people with Liver Metastasis and Cancer, run by University Health Network, Toronto at 1 site in Canada.
Trial summary
Cancers that have spread to the liver from the primary cancer location (liver metastases) that cannot be removed surgically (unresectable) can be treated with chemotherapy and/or radiation therapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Liver Metastasis, Cancer
- What is being tested?
- Sorafenib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- 1 siteCanada
- Study dates
- Nov 2008to 8 Sep 2020
- 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
- Histologically confirmed liver metastases
- Largest burden of disease should be hepatic if there's extrahepatic disease exists
- Tumour should be medically inoperable
- Patient have a life expectancy of at least 3 months and a KPS performance status of at least 60%.
- Patient should be 18 years of age or older
- Patient should have adequate organ function
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- Patient have Creatinine ≤ 2 times upper limit of normal range
- Patient recovered from the effects of prior therapy
- Patient (or person representing the patient) should be able to give informed consent
- Patient have Child's A score (5 or 6) score
- For women of childbearing age, birth control is being used and the pregnancy test is negative
Who cannot join
- No major surgery in the past 4 weeks.
- No previous use of sorafenib previously.
- Patient should not have or is receiving systemic therapy or investigational agents within 2 weeks of radiotherapy
- No previous upper abdominal radiation therapy to the liver.
- No serious medical conditions that may be aggravated by treatment, including but not limited to: myocardial infarction within 6 months, congestive cardiac failure, unstable angina, active cardiomyopathy, unstable ventricular arrhythmia, uncontrolled hypertension, uncontrolled psychotic disorders,serious infections, active peptic ulcer disease, active liver disease or previous stroke.
- Patients who are infected with human immunodeficiency virus (HIV), should not be receiving combination anti-retroviral therapy
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- No clinically significant liver failure (i.e. encephalopathy or ascites found clinically).
- No thrombolytic therapy within 4 weeks or are they receiving other anticoagulant therapy.
- No underlying cirrhosis with Child's B or C score.
- No history of uncontrolled, life threatening malignancy within the past 6 months.
- Patient should not have a variceal bleed or other gastrointestinal bleed in the past 2 months.
- No brain metastases
- Patient should not be pregnant.
- Patients on Rifampin, St. John's Wort, Phenytoin, Carbamazepine, Phenobarbital, or Chronic use (more than 4 weeks) of dexamethasone
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase I/II Trial of Radiation Therapy and Sorafenib for Treatment of Unresectable Liver Metastases
Cancers that have spread to the liver from the primary cancer location (liver metastases) that cannot be removed surgically (unresectable) can be treated with chemotherapy and/or radiation therapy. Previous research has shown that tumours often have abnormal blood vessels that may reduce the effect of radiation therapy. New drugs, known as "anti-angiogenic" drugs have been shown in animal and human studies to damage or change tumour blood vessels in ways that may make tumors more sensitive to radiation treatment. 32- 44 Patients diagnosed with unresectable liver metastasis will be invited to take part in this study. The purpose of this study is to investigate the use of a new anti-angiogenic drug called Sorafenib, in combination radiation therapy and chemotherapy. The study will test how effective the new treatment is, the side effects associated with the new treatment, and to help establish safe dosages of the study medication.
Read the detailed description
In this study, Stereotactic Body Radiation Therapy(SBRT) and Whole Liver Radiotherapy (WLRT) will be used concurrently with sorafenib at 3 different dosages to determine the tolerability and efficacy of this combined treatment. Sorafenib doses will be 200mg twice daily orally for 28 days in level I, 400 mg in the morning and 200mg in the evening in level II, and 400mg twice daily orally for 28 days in level III . Radiotherapy will be started at day 8, patients will receive a total of 6 fractions over 2 weeks. Patients will be assessed weekly during treatment, 1 month post-tx, then at 3-month intervals for up to a year after tx, and then followed-up at 6-month intervals up to 3 years. Once the Maximum Tolerated Dose (MTD) is established, an expanded cohort for each stratum will accrue such that a total of 10 patients per strata. This will allow us to gain further experience with this regimen and consolidate the safety and efficacy data. Quality of Life (QOL) assessment will be carried out at baseline and 1/3/6/9 mos post-tx. Patients will also be offered correlative studies looking at biomarkers through tissue, blood, and urine samples, and an imaging study looking at tissue perfusion.
- Conditions
- Liver Metastasis, Cancer
- Being tested
- Sorafenib
- Keywords
- Liver metastasis, sorafenib, Liver metastasis from cancer
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SorafenibDrug
Sorafenib doses will be 200mg twice daily orally for 28 days in level I, 400 mg in the morning and 200mg in the evening in level II, and 400mg twice daily orally for 28 days in level III . Radiotherapy will be started at day 8, patients will receive a total of 6 fractions over 2 weeks. Patients will be assessed weekly during treatment, 1 month post-tx, then at 3-month intervals for up to a year after tx, and then followed-up at 6-month intervals up to 3 years.
| Study group | Role | What they receive |
|---|---|---|
| Sorafenib + RT | Experimental | Not described Receives: Drug: Sorafenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine the MTD of sorafenib and RT in patients with liver metastases using an iso-toxicity radiation dose allocation scheme. Determine the acute toxicity (< 3 months) of sorafenib when combined with RT in patients with liver metastases.
Measured: 2 years enrollment; 3 years follow-up
Secondary outcomes (1)
Document any observed late toxicities of treatment. Determine 1) the in-field local control based on CT response at 3 months;2)the time to progression and overall survival of this cohort, 3)changes in quality of life in these patients
Measured: 2 years enrollment; 3 years follow-up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 May 2009 (estimated)
- Study startNov 2008
- Primary completion8 Sep 2020
- Study completion8 Sep 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Liver MetastasisStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 54 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Laura Dawson, MD, Principal investigator, University Health Centre, Princess Margaret Cancer Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00892424
- Sponsor's protocol ID
- UHN REB 08-0598-C
- Status last verified
- Sep 2020
- First submitted
- 1 May 2009
- Last updated
- 10 Sep 2020
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 10 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Trial of Radiation Therapy and Sorafenib for Treatment of Unresectable Liver Metastases
- ClinicalTrials.gov ID
- NCT00892424
- Acronym / sponsor ID
- UHN REB 08-0598-C
- Conditions
- Liver Metastasis, Cancer
- Keywords
- Liver metastasis, sorafenib, Liver metastasis from cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 54 participants (actual)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Study start
- Nov 2008 (actual)
- Primary completion
- 8 Sep 2020 (actual)
- Study completion
- 8 Sep 2020 (actual)
- First posted
- 4 May 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Cancers that have spread to the liver from the primary cancer location (liver metastases) that cannot be removed surgically (unresectable) can be treated with chemotherapy and/or radiation therapy. Previous research has shown that tumours often have abnormal blood vessels that may reduce the effect of radiation therapy. New drugs, known as "anti-angiogenic" drugs have been shown in animal and human studies to damage or change tumour blood vessels in ways that may make tumors more sensitive to radiation treatment. 32- 44 Patients diagnosed with unresectable liver metastasis will be invited to take part in this study. The purpose of this study is to investigate the use of a new anti-angiogenic drug called Sorafenib, in combination radiation therapy and chemotherapy. The study will test how effective the new treatment is, the side effects associated with the new treatment, and to help establish safe dosages of the study medication.
Detailed description
In this study, Stereotactic Body Radiation Therapy(SBRT) and Whole Liver Radiotherapy (WLRT) will be used concurrently with sorafenib at 3 different dosages to determine the tolerability and efficacy of this combined treatment. Sorafenib doses will be 200mg twice daily orally for 28 days in level I, 400 mg in the morning and 200mg in the evening in level II, and 400mg twice daily orally for 28 days in level III . Radiotherapy will be started at day 8, patients will receive a total of 6 fractions over 2 weeks. Patients will be assessed weekly during treatment, 1 month post-tx, then at 3-month intervals for up to a year after tx, and then followed-up at 6-month intervals up to 3 years. Once the Maximum Tolerated Dose (MTD) is established, an expanded cohort for each stratum will accrue such that a total of 10 patients per strata. This will allow us to gain further experience with this regimen and consolidate the safety and efficacy data. Quality of Life (QOL) assessment will be carried out at baseline and 1/3/6/9 mos post-tx. Patients will also be offered correlative studies looking at biomarkers through tissue, blood, and urine samples, and an imaging study looking at tissue perfusion.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sorafenib + RT | Experimental | Drug: Sorafenib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Histologically confirmed liver metastases
- Largest burden of disease should be hepatic if there's extrahepatic disease exists
- Tumour should be medically inoperable
- Patient have a life expectancy of at least 3 months and a KPS performance status of at least 60%.
- Patient should be 18 years of age or older
Key exclusion criteria (14 listed)
- No major surgery in the past 4 weeks.
- No previous use of sorafenib previously.
- Patient should not have or is receiving systemic therapy or investigational agents within 2 weeks of radiotherapy
- No previous upper abdominal radiation therapy to the liver.
- No serious medical conditions that may be aggravated by treatment, including but not limited to: myocardial infarction within 6 months, congestive cardiac failure, unstable angina, active cardiomyopathy, unstable ventricular arrhythmia, uncontrolled hypertension, uncontrolled psychotic disorders,serious infections, active peptic ulcer disease, active liver disease or previous stroke.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SorafenibSorafenib doses will be 200mg twice daily orally for 28 days in level I, 400 mg in the morning and 200mg in the evening in level II, and 400mg twice daily orally for 28 days in level III . Radiotherapy will be started at day 8, patients will receive a total of 6 fractions over 2 weeks. Patients will be assessed weekly during treatment, 1 month post-tx, then at 3-month intervals for up to a year after tx, and then followed-up at 6-month intervals up to 3 years. | Drug | Sorafenib + RT |
Primary outcome
Determine the MTD of sorafenib and RT in patients with liver metastases using an iso-toxicity radiation dose allocation scheme. Determine the acute toxicity (< 3 months) of sorafenib when combined with RT in patients with liver metastases.
Time frame: 2 years enrollment; 3 years follow-up
1 secondary outcome
Document any observed late toxicities of treatment. Determine 1) the in-field local control based on CT response at 3 months;2)the time to progression and overall survival of this cohort, 3)changes in quality of life in these patients
Time frame: 2 years enrollment; 3 years follow-up
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Sep 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Laura Dawson, MD principal investigator
University Health Centre, Princess Margaret Cancer Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Sorafenib in people with Liver Metastasis and Cancer, run by University Health Network, Toronto 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 11 inclusion and 14 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 10 Sep 2020. 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?
Determine the MTD of sorafenib and RT in patients with liver metastases using an iso-toxicity radiation dose allocation scheme. Determine the acute toxicity (< 3 months) of sorafenib when combined with RT in patients with liver metastases. (time frame: 2 years enrollment; 3 years follow-up). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 10 Sep 2020.