Oligometastases of the LIVer Treated With Chemotherapy With ou Without Extracranial Stereotactic Body Radiation Therapy in Patients With Colorectal Cancer (OLIVER)
Primary Purpose
Liver Metastases, Colorectal Cancer
Status
Withdrawn
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
SBRT
Chemotherapy
Sponsored by
About this trial
This is an interventional treatment trial for Liver Metastases focused on measuring Oligometastatis, SBRT
Eligibility Criteria
Inclusion Criteria:
- Male or female with age ≥18 years and <85 years;
- Patient with histologically proven colorectal cancer;
- Patient with a curative surgical treatment (R0) of the primary tumor performed;
- Oligometastatic disease defined as 1 to 3 liver-only metastases (measurable lesion as per RECIST 1.1);
- Patient unfit for surgery or with unresectable metastases;
- Maximal diameter of largest metastasis: 30 mm;
- Patient naïve of chemotherapy in the metastatic setting or after a first-line of chemotherapy for metastatic disease but not having progressed up to 1 year (i.e. slowly progressing disease);
- WHO status 0-1;
- Adequate liver function: bilirubin <3 mg/dL, albumin >2.5 g/dL;
- Adequate hematological function: absolute neutrophil count (ANC) >1.5 x 10⁹/L; platelets >100 x 10⁹/L, hemoglobin (Hb) >9 g/dL;
- Normal PT (>70%) and PTT except if the patient uses anticoagulants;
- Liver enzymes <3 times upper limit of normal;
- Renal function must be adequate for infusion of iv. contrast agent for CT-scan according to the local policy;
- Woman of childbearing potential and male patients must agree to use adequate contraception for the duration of study and up to 3 months following completion of therapy;
- Patient who have received the information sheet, dated and signed the informed consent form;
- Affiliated to the social security system.
Exclusion Criteria:
- Healthy liver volume<700 mL
- Life expectancy <3 months;
- Patient fit for metastasectomy or hepatectomy;
- Extrahepatic metastases;
- Cirrhosis with Child Pugh score B or C;
- More than one line of chemotherapy in the metastatic setting or rapidly progressing disease;
- Previous local treatment of liver metastases;
- Treatment with any other investigational agent against cancer;
- Malignancies other than mCRC within 5 years prior to randomization, except for adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, and ductal carcinoma in situ treated surgically with curative intent;
- Pregnant woman or breast feeding mother;
- Patient deprived of liberty or placed under the authority of a tutor. Patient with any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial. Patient unable to understand the purpose of the study (language, etc.).
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Chemotherapy + SBRT
Chemotherapy
Arm Description
Patients will received 2 courses of chemotherapy before SBRT if no hepatic or extra-hepatic progression identified. All liver metastases will be irradiated. 4 doses prescription are allowed (according to the center, and the technique uded and the dosimetric constraints): 3x15 Gy, 4 x 15 Gy, 5 x10 Gy or 5 x 8 Gy. The remaining courses of chemotherapy 2 to 3 weeks after completion of SBRT will be administered
Patients will receive chemotherapy as initially scheduled
Outcomes
Primary Outcome Measures
Progression Free Survival
To evaluate the impact of SBRT on Progression-Free Survival (PFS) at 1 year according to RECIST 1.1
Secondary Outcome Measures
Local Control rate
Defined as the time from the date of randomization to the date of a documented loco-regional event
Overall survival
Defined as the time from the date of randomization to the date of documented death of any cause
Cancer specific survival
Defined as the time from the date of randomization to the date of documented death from cancer or complication from treatment
CTCAE Toxicity Assessment
Acute/ late toxicity will be assessed according to the flowchart and performed based on CTCAE V4
Quality of life EORTC QLQ C30
Will be assessed using self-administered questionnaires EORTC QLQ C30
Quality of life EORTC QLQ CR29
Will be assessed using self-administered questionnaire QLQ CR29
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03532204
Brief Title
Oligometastases of the LIVer Treated With Chemotherapy With ou Without Extracranial Stereotactic Body Radiation Therapy in Patients With Colorectal Cancer
Acronym
OLIVER
Official Title
Oligometastases of the LIVer Treated With Chemotherapy With ou Without Extracranial Stereotactic Body Radiation Therapy in Patients With Colorectal Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
May 2019
Overall Recruitment Status
Withdrawn
Why Stopped
no participants enrolled
Study Start Date
April 15, 2019 (Anticipated)
Primary Completion Date
December 15, 2021 (Anticipated)
Study Completion Date
August 15, 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
UNICANCER
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The role of radiotherapy in metastatic cancer has historically been limited to palliation while metastasectomy or radiofrequency has emerged as playing a major role in disease control. Although resection is the standard of care for liver metastasis, 80-90% of patients are not resectable at diagnosis in particular because of the presence of oligometastases. Factors that favour a truly oligometastatic state include a long latent interval between the treatment of the primary tumor and the appearance of metastases.
Oligometastatic cancer is a very heterogeneous disease with respect to several factors including the location of the primary tumor. With the advent of extracranial stereotactic body radiation therapy (SBRT), higher biological equivalent doses can be safely delivered in 3 to 5 fractions, thus potentially ablating all the tissue in the treated area while protecting more efficiently the hosting organ and healthy tissues surrounding the tumors.
In patients with liver oligometastases, in-field local control rates at 2 years range from 70% to 90% with less than 5% severe grade 3 or higher toxicity rates. Retrospective studies indicate that roughly 20% of the patients remain disease-free 2 to 4 years after SBRT.
For patients treated with SBRT some authors found that half of the patients had either no metastatic progression or very little progression in terms of number and site of metastases. The patterns of failure after SBRT for oligometastases in one organ showed that 73% of patients eventually developed new metastases with higher than 80% occurring as new metastases in the same index organ. These findings support the idea of an oligometastatic state in which aggressive local therapy could improve progression-free survival (PFS).
With this phase III study, we sought to evaluate the impact of SBRT on PFS at 2 years in patients with synchronous or metachronous liver-only oligometastases from colorectal cancers patients after a first line chemotherapy for metastatic disease but not having progressed during first line chemotherapy and up to 1 year
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Liver Metastases, Colorectal Cancer
Keywords
Oligometastatis, SBRT
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Chemotherapy + SBRT
Arm Type
Experimental
Arm Description
Patients will received 2 courses of chemotherapy before SBRT if no hepatic or extra-hepatic progression identified.
All liver metastases will be irradiated. 4 doses prescription are allowed (according to the center, and the technique uded and the dosimetric constraints): 3x15 Gy, 4 x 15 Gy, 5 x10 Gy or 5 x 8 Gy.
The remaining courses of chemotherapy 2 to 3 weeks after completion of SBRT will be administered
Arm Title
Chemotherapy
Arm Type
Active Comparator
Arm Description
Patients will receive chemotherapy as initially scheduled
Intervention Type
Radiation
Intervention Name(s)
SBRT
Intervention Description
Patients will received 2 courses of chemotherapy before SBRT if no hepatic or extra-hepatic progression identified.
All liver metastases will be irradiated. 4 doses prescription are allowed (according to the center, and the technique uded and the dosimetric constraints): 3x15 Gy, 4 x 15 Gy, 5 x10 Gy or 5 x 8 Gy.
The remaining courses of chemotherapy 2 to 3 weeks after completion of SBRT will be administered
Intervention Type
Drug
Intervention Name(s)
Chemotherapy
Intervention Description
At investigator's discretion
Primary Outcome Measure Information:
Title
Progression Free Survival
Description
To evaluate the impact of SBRT on Progression-Free Survival (PFS) at 1 year according to RECIST 1.1
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Local Control rate
Description
Defined as the time from the date of randomization to the date of a documented loco-regional event
Time Frame
1 and 3 years
Title
Overall survival
Description
Defined as the time from the date of randomization to the date of documented death of any cause
Time Frame
3 years
Title
Cancer specific survival
Description
Defined as the time from the date of randomization to the date of documented death from cancer or complication from treatment
Time Frame
3 years
Title
CTCAE Toxicity Assessment
Description
Acute/ late toxicity will be assessed according to the flowchart and performed based on CTCAE V4
Time Frame
up to 24 weeks
Title
Quality of life EORTC QLQ C30
Description
Will be assessed using self-administered questionnaires EORTC QLQ C30
Time Frame
up to 24 weeks
Title
Quality of life EORTC QLQ CR29
Description
Will be assessed using self-administered questionnaire QLQ CR29
Time Frame
up to 24 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female with age ≥18 years and <85 years;
Patient with histologically proven colorectal cancer;
Patient with a curative surgical treatment (R0) of the primary tumor performed;
Oligometastatic disease defined as 1 to 3 liver-only metastases (measurable lesion as per RECIST 1.1);
Patient unfit for surgery or with unresectable metastases;
Maximal diameter of largest metastasis: 30 mm;
Patient naïve of chemotherapy in the metastatic setting or after a first-line of chemotherapy for metastatic disease but not having progressed up to 1 year (i.e. slowly progressing disease);
WHO status 0-1;
Adequate liver function: bilirubin <3 mg/dL, albumin >2.5 g/dL;
Adequate hematological function: absolute neutrophil count (ANC) >1.5 x 10⁹/L; platelets >100 x 10⁹/L, hemoglobin (Hb) >9 g/dL;
Normal PT (>70%) and PTT except if the patient uses anticoagulants;
Liver enzymes <3 times upper limit of normal;
Renal function must be adequate for infusion of iv. contrast agent for CT-scan according to the local policy;
Woman of childbearing potential and male patients must agree to use adequate contraception for the duration of study and up to 3 months following completion of therapy;
Patient who have received the information sheet, dated and signed the informed consent form;
Affiliated to the social security system.
Exclusion Criteria:
Healthy liver volume<700 mL
Life expectancy <3 months;
Patient fit for metastasectomy or hepatectomy;
Extrahepatic metastases;
Cirrhosis with Child Pugh score B or C;
More than one line of chemotherapy in the metastatic setting or rapidly progressing disease;
Previous local treatment of liver metastases;
Treatment with any other investigational agent against cancer;
Malignancies other than mCRC within 5 years prior to randomization, except for adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, and ductal carcinoma in situ treated surgically with curative intent;
Pregnant woman or breast feeding mother;
Patient deprived of liberty or placed under the authority of a tutor. Patient with any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial. Patient unable to understand the purpose of the study (language, etc.).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stéphanie SERVAGI, MD
Organizational Affiliation
INSTITUT JEAN GODINOT, REIMS
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Gilles CREHANGE, MD
Organizational Affiliation
CENTRE GEORGES FRANCOIS LECLERC, DIJON
Official's Role
Principal Investigator
12. IPD Sharing Statement
Learn more about this trial
Oligometastases of the LIVer Treated With Chemotherapy With ou Without Extracranial Stereotactic Body Radiation Therapy in Patients With Colorectal Cancer
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