Liver MetastasesOLIVERNCT03532204
Oligometastases of the LIVer Treated With Chemotherapy With ou Without Extracranial Stereotactic Body Radiation Therapy in Patients With Colorectal Cancer
A study testing SBRT and Chemotherapy in people with Liver Metastases and Colorectal Cancer, run by UNICANCER.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Liver Metastases, Colorectal Cancer
- What is being tested?
- SBRT and Chemotherapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 15 Apr 2019to 15 Aug 2023
- Phase
- Interventional
- 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 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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;
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- 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.
Who cannot join
- 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;
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- 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.).
About this study
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.
Read more
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
- Conditions
- Liver Metastases, Colorectal Cancer
- Being tested
- SBRT, Chemotherapy
- Keywords
- Oligometastatis, SBRT
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SBRTRadiation
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
ChemotherapyDrug
At investigator's discretion
| Study group | Role | What they receive |
|---|---|---|
| Chemotherapy + SBRT | Experimental | 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 Receives: Radiation: SBRT; Drug: Chemotherapy |
| Chemotherapy | Active comparator | Patients will receive chemotherapy as initially scheduled Receives: Drug: Chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival
To evaluate the impact of SBRT on Progression-Free Survival (PFS) at 1 year according to RECIST 1.1
Measured: 1 year
Secondary outcomes (6)
Local Control rate
Defined as the time from the date of randomization to the date of a documented loco-regional event
Measured: 1 and 3 years
Overall survival
Defined as the time from the date of randomization to the date of documented death of any cause
Measured: 3 years
Cancer specific survival
Defined as the time from the date of randomization to the date of documented death from cancer or complication from treatment
Measured: 3 years
CTCAE Toxicity Assessment
Acute/ late toxicity will be assessed according to the flowchart and performed based on CTCAE V4
Measured: up to 24 weeks
Quality of life EORTC QLQ C30
Will be assessed using self-administered questionnaires EORTC QLQ C30
Measured: up to 24 weeks
Quality of life EORTC QLQ CR29
Will be assessed using self-administered questionnaire QLQ CR29
Measured: up to 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 May 2018
- Study start15 Apr 2019 (estimated)
- Primary completion15 Dec 2021 (estimated)
- Study completion15 Aug 2023 (estimated)
Why it stopped: no participants enrolled
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Liver MetastasesStudies of the same condition, open and under way.
- More trials run by UNICANCERThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- UNICANCER
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Stéphanie SERVAGI, MD, Principal investigator, INSTITUT JEAN GODINOT, REIMSGilles CREHANGE, MD, Principal investigator, CENTRE GEORGES FRANCOIS LECLERC, DIJON
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03532204
- Sponsor's protocol ID
- UC-0107/1602
- Acronym
- OLIVER
- Status last verified
- May 2019
- First submitted
- 25 Jan 2018
- Last updated
- 22 May 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Oligometastases of the LIVer Treated With Chemotherapy With ou Without Extracranial Stereotactic Body Radiation Therapy in Patients With Colorectal Cancer
- ClinicalTrials.gov ID
- NCT03532204
- Acronym / sponsor ID
- OLIVER / UC-0107/1602
- Conditions
- Liver Metastases, Colorectal Cancer
- Keywords
- Oligometastatis, SBRT
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: no participants enrolled
- Enrolment
- 0 participants (actual)
- Lead sponsor
- UNICANCERUniversity, hospital or other
- Study start
- 15 Apr 2019 (estimated)
- Primary completion
- 15 Dec 2021 (estimated)
- Study completion
- 15 Aug 2023 (estimated)
- First posted
- 22 May 2018 (actual)
- 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.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Chemotherapy + SBRT | Experimental | Radiation: SBRT, Drug: ChemotherapyPatients 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 |
| Chemotherapy | Active comparator | Drug: ChemotherapyPatients will receive chemotherapy as initially scheduled |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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;
Key exclusion criteria (11 listed)
- 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;
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 |
|---|---|---|
| SBRTPatients 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 | Radiation | Chemotherapy + SBRT |
| ChemotherapyAt investigator's discretion | Drug | Chemotherapy, Chemotherapy + SBRT |
Primary outcome
Progression Free Survival
Time frame: 1 year
To evaluate the impact of SBRT on Progression-Free Survival (PFS) at 1 year according to RECIST 1.1
6 secondary outcomes
Local Control rate
Time frame: 1 and 3 years
Overall survival
Time frame: 3 years
Cancer specific survival
Time frame: 3 years
CTCAE Toxicity Assessment
Time frame: up to 24 weeks
Quality of life EORTC QLQ C30
Time frame: up to 24 weeks
Quality of life EORTC QLQ CR29
Time frame: up to 24 weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2019.
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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.
Stéphanie SERVAGI, MD principal investigator
INSTITUT JEAN GODINOT, REIMS
Gilles CREHANGE, MD principal investigator
CENTRE GEORGES FRANCOIS LECLERC, DIJON
Questions about this trial
What is this clinical trial studying?
A study testing SBRT and Chemotherapy in people with Liver Metastases and Colorectal Cancer, run by UNICANCER.
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 16 inclusion and 11 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: withdrawn, as of the sponsor's last update on 22 May 2019. Status can change between updates, so confirm with the study contact before making plans.
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.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Progression Free Survival (time frame: 1 year). 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 22 May 2019.