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Sorafenib-RT Treatment for Liver Metastasis (SLIM)

Primary Purpose

Liver Metastasis, Cancer

Status

Completed

Phase

Phase 1

Locations

Canada

Study Type

Interventional

Intervention

Sorafenib

About this trial

This is an interventional treatment trial for Liver Metastasis focused on measuring Liver metastasis, sorafenib, Liver metastasis from cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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
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

Exclusion Criteria:

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
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

Sites / Locations

University Health Network

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Sorafenib + RT

Arm Description

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

Full Information

NCT ID

NCT00892424

First Posted

May 1, 2009

Last Updated

September 8, 2020

Sponsor

University Health Network, Toronto

1. Study Identification

Unique Protocol Identification Number

NCT00892424

Brief Title

Sorafenib-RT Treatment for Liver Metastasis (SLIM)

Official Title

Phase I/II Trial of Radiation Therapy and Sorafenib for Treatment of Unresectable Liver Metastases

Study Type

Interventional

2. Study Status

Record Verification Date

September 2020

Overall Recruitment Status

Completed

Study Start Date

November 2008 (Actual)

Primary Completion Date

September 8, 2020 (Actual)

Study Completion Date

September 8, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University Health Network, Toronto

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Liver Metastasis, Cancer

Keywords

Liver metastasis, sorafenib, Liver metastasis from cancer

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

54 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Sorafenib + RT

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

Sorafenib

Intervention Description

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.

Primary Outcome Measure Information:

Title

Time Frame

2 years enrollment; 3 years follow-up

Secondary Outcome Measure Information:

Title

Time Frame

2 years enrollment; 3 years follow-up

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 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 Exclusion Criteria: 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 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Laura Dawson, MD

Organizational Affiliation

University Health Centre, Princess Margaret Cancer Centre

Official's Role

Principal Investigator

Facility Information:

Facility Name

University Health Network

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M5G 2M9

Country

Canada

12. IPD Sharing Statement

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Sorafenib-RT Treatment for Liver Metastasis (SLIM)

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