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Stereotactic Radiotherapy (SRT) Liver (COLD 1)

Primary Purpose

Liver Neoplasms, Neoplasm Metastases

Status
Completed
Phase
Phase 1
Locations
Canada
Study Type
Interventional
Intervention
Stereotactic radiotherapy (SRT) or highly conformal (CRT)
Sponsored by
University Health Network, Toronto
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Liver Neoplasms

Eligibility Criteria

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

Inclusion Criteria: Primary hepatobiliary confirmed pathologically or via imaging Liver metastases from colorectal cancer or other solid malignancy, confirmed pathologically New radiographic liver lesions most consistent with metastases, in a patient with previously pathologically proven solid malignancy and a previously negative liver contrast CT or MRI The tumor must be unresectable or the patient must be medically inoperable or extra-hepatic metastases must be present Karnofsky performance status (KPS) > 60 Age > 18 years Patients must have recovered from the effects of previous surgery, radiotherapy or chemotherapy Chemotherapy must be completed at least 2 weeks prior to radiation therapy or not planned to be administered for at least 2 weeks Adequate organ function as assessed as follows:Hemoglobin > 90 g/L, Absolute neutrophil count > 1.5 bil/L, Platelets > 80,000 bil/L, Bilirubin < 3.0 times upper range of normal, INR < 1.3 or correctable with vitamin K, AST or ALT < 6.0 times upper range of normal, Creatinine < 200 umol/L (other than patients who are having dialysis or already have dialysis lines in place for future dialysis for renal failure. These patients may be treated on study with no upper limit on their creatinine.) Child A liver score Previous liver resection or ablative therapy is permitted. Life expectancy > 3 months Multiple metastases are permitted (volume of uninvolved must be at least 800 cc, and the maximal effective liver volume that may be treated is 80%. Informed consent form Exclusion Criteria: Patients with active hepatitis or clinically significant liver failure Prior radiation therapy to the right upper abdomen, precluding re-irradiation of the liver. (Prior pelvic radiation is permitted, as long as no overlap between pelvic and liver radiation fields occurs.) Prior uncontrolled, life threatening malignancy within the past year. Gross (clinically apparent) ascites. Pregnancy is not permitted, and in women of child bearing age, a pregnancy test and birth control are warranted.

Sites / Locations

  • Princess Margaret Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Stereotactic RT or highly conformal RT

Arm Description

Outcomes

Primary Outcome Measures

Phase I: To evaluate feasibility and maximally tolerated dose of SRT
Phase II: To determine with more confidence the rate and spectrum of all toxicities that occur at the maximally tolerated dose of radiation.

Secondary Outcome Measures

To evaluate local control, progression-free survival and survival of patients with unresectable primary hepatobiliary cancer and metastatic liver cancer treated with SRT.
To evaluate the quality of life.
To evaluate changes in liver function following SRT.
To evaluate patterns of breathing at and during RT.
To develop more confidence in a revised normal tissue complication probability (NTCP) model for radiation induced liver toxicity and collect preliminary data to determine how the liver responds to radiation.
To determine whether serum cytokines and P-III-P can help predict RILD.

Full Information

First Posted
September 8, 2005
Last Updated
August 13, 2020
Sponsor
University Health Network, Toronto
Collaborators
American Society of Clinical Oncology
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1. Study Identification

Unique Protocol Identification Number
NCT00152906
Brief Title
Stereotactic Radiotherapy (SRT) Liver (COLD 1)
Official Title
Phase I/II Trial of Highly Conformal Radiotherapy for Unresectable Liver Metastases and Hepatobiliary Carcinoma
Study Type
Interventional

2. Study Status

Record Verification Date
August 2020
Overall Recruitment Status
Completed
Study Start Date
July 2003 (undefined)
Primary Completion Date
July 2016 (Actual)
Study Completion Date
July 10, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Health Network, Toronto
Collaborators
American Society of Clinical Oncology

4. Oversight

5. Study Description

Brief Summary
A minority of patients with colorectal liver metastases and hepatobiliary cancer (primary liver cancer) are candidates for surgery, but there are no curative treatment options for these patients. Their median survival time is 3 to 12 months. Stereotactic radiation (SRT) (highly conformal radiotherapy (CRT)) is a treatment option for these patients with unresectable liver cancer, now possible due to improvements in our ability to localize and immobilize liver tumors and an improved understanding of the partial liver volume tolerance to radiation. SRT should permit liver tumors to be treated to tumorcidal doses while sparing the uninvolved liver, decreasing the risk of treatment related normal tissue toxicity. With such conformal radiation, it is possible to deliver radiation in fewer fractions than traditionally required, which should be more convenient for patients. In this study, CRT will be delivered during shallow breathing or breath hold to minimize organ motion due to breathing, decreasing the volume of normal liver that must be irradiated.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Liver Neoplasms, Neoplasm Metastases

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
140 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Stereotactic RT or highly conformal RT
Arm Type
Experimental
Intervention Type
Procedure
Intervention Name(s)
Stereotactic radiotherapy (SRT) or highly conformal (CRT)
Intervention Description
SRT or CRT is radiation delivered precisely conforming the high dose region to the tumor, usually in a few highdose fractions.
Primary Outcome Measure Information:
Title
Phase I: To evaluate feasibility and maximally tolerated dose of SRT
Time Frame
assessment: weekly during treatment; 1, 3, 6, 9, 12 months post, every 6 months for up to 3 years
Title
Phase II: To determine with more confidence the rate and spectrum of all toxicities that occur at the maximally tolerated dose of radiation.
Time Frame
assessment: weekly during treatment; 1, 3, 6, 9, 12 months post, every 6 months for up to 3 years
Secondary Outcome Measure Information:
Title
To evaluate local control, progression-free survival and survival of patients with unresectable primary hepatobiliary cancer and metastatic liver cancer treated with SRT.
Time Frame
assessment: weekly during treatment; 1, 3, 6, 9, 12 months post, every 6 months for up to 3 years
Title
To evaluate the quality of life.
Time Frame
assessment: pre-treatement, 1, 3, 6,12 months post
Title
To evaluate changes in liver function following SRT.
Time Frame
3 to 12 months
Title
To evaluate patterns of breathing at and during RT.
Time Frame
during radiation treatment only
Title
To develop more confidence in a revised normal tissue complication probability (NTCP) model for radiation induced liver toxicity and collect preliminary data to determine how the liver responds to radiation.
Time Frame
at 3 months post RT
Title
To determine whether serum cytokines and P-III-P can help predict RILD.
Time Frame
baseline, during radiation and up to 3 months post radiation

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Primary hepatobiliary confirmed pathologically or via imaging Liver metastases from colorectal cancer or other solid malignancy, confirmed pathologically New radiographic liver lesions most consistent with metastases, in a patient with previously pathologically proven solid malignancy and a previously negative liver contrast CT or MRI The tumor must be unresectable or the patient must be medically inoperable or extra-hepatic metastases must be present Karnofsky performance status (KPS) > 60 Age > 18 years Patients must have recovered from the effects of previous surgery, radiotherapy or chemotherapy Chemotherapy must be completed at least 2 weeks prior to radiation therapy or not planned to be administered for at least 2 weeks Adequate organ function as assessed as follows:Hemoglobin > 90 g/L, Absolute neutrophil count > 1.5 bil/L, Platelets > 80,000 bil/L, Bilirubin < 3.0 times upper range of normal, INR < 1.3 or correctable with vitamin K, AST or ALT < 6.0 times upper range of normal, Creatinine < 200 umol/L (other than patients who are having dialysis or already have dialysis lines in place for future dialysis for renal failure. These patients may be treated on study with no upper limit on their creatinine.) Child A liver score Previous liver resection or ablative therapy is permitted. Life expectancy > 3 months Multiple metastases are permitted (volume of uninvolved must be at least 800 cc, and the maximal effective liver volume that may be treated is 80%. Informed consent form Exclusion Criteria: Patients with active hepatitis or clinically significant liver failure Prior radiation therapy to the right upper abdomen, precluding re-irradiation of the liver. (Prior pelvic radiation is permitted, as long as no overlap between pelvic and liver radiation fields occurs.) Prior uncontrolled, life threatening malignancy within the past year. Gross (clinically apparent) ascites. Pregnancy is not permitted, and in women of child bearing age, a pregnancy test and birth control are warranted.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Laura Dawson, MD
Organizational Affiliation
Princess Margaret Hospital, Canada
Official's Role
Principal Investigator
Facility Information:
Facility Name
Princess Margaret Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada

12. IPD Sharing Statement

Citations:
PubMed Identifier
23547075
Citation
Bujold A, Massey CA, Kim JJ, Brierley J, Cho C, Wong RK, Dinniwell RE, Kassam Z, Ringash J, Cummings B, Sykes J, Sherman M, Knox JJ, Dawson LA. Sequential phase I and II trials of stereotactic body radiotherapy for locally advanced hepatocellular carcinoma. J Clin Oncol. 2013 May 1;31(13):1631-9. doi: 10.1200/JCO.2012.44.1659. Epub 2013 Apr 1.
Results Reference
derived

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Stereotactic Radiotherapy (SRT) Liver (COLD 1)

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