Colorectal CancerPhase 3NCT01895257
Comparing HAI-90Y (SIR-spheres)+Chemotx LV5FU2 Versus Chemotx LV5FU2 Alone to Treat Colorectal Cancer
A Phase 3 study testing HAI-90Y radioembolization (SIR-spheres injection) and systemic chemotherapy LV5FU2 in people with Colorectal Cancer, run by Universiteit Antwerpen at 10 sites in Belgium.
Trial summary
The investigators propose to conduct a randomised phase III trial evaluating a maintenance strategy comparing hepatic arterial injection of Yttrium-90 resin microspheres plus continuing simplified chemotherapy with/without targeted therapy versus continuing simplified chemotherapy with/without targeted therapy alone… Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- HAI-90Y radioembolization (SIR-spheres injection) and systemic chemotherapy LV5FU2
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 162 participants
- Where
- 10 sitesBelgium
- Study dates
- Aug 2013to Dec 2018
- Phase
- Phase 3
- 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 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Willing and able to provide written informed consent
- Histologically confirmed adenocarcinoma of the colon or rectum, with or without primary tumour in situ. Unequivocal and measurable (RECIST 1.1) CT evidence of liver metastases which are not treatable by surgical resection and/or local ablation with curative intent at the time of trial entry.
- Partial response or stable disease (RECIST 1.1 criteria, controlled metastatic disease) after chemotherapy induction with oxaliplatin and/or irinotecan based induction chemotherapy (doublet or triplet combinations) +/- targeted therapies during 3 to 6 months.
- Trial inclusion must be performed between 3 and 6 months since the date of the first course of chemotherapy (induction) administration.
- Limited extra-hepatic metastases in the lung and/or lymph nodes are permitted. Metastases in the lung must either be not more than five nodules in number with no individual nodule more than 1 cm in diameter or 1 single lesion of up to 1.7 cm in diameter. Involvement of lymph nodes in 1 single anatomic region (pelvis, abdomen or chest) are permitted provided their longest diameter measures less than 2 cm.
- All imaging evidence used as part of the screening process must be within 28 days prior to the time of randomisation.
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- Suitable for either treatment regimen as determined by clinical assessment undertaken by the Investigator.
- Patients may have received adjuvant chemotherapy or (neo-) adjuvant chemo-radiotherapy to the pelvis, provided the last dose of chemotherapy was administered at least 6 months prior to begin chemotherapy induction. Previous radiotherapy to the pelvis is not an exclusion criterion.
- WHO performance status 0 - 1
- Adequate hematological, renal and hepatic function as follows:
- Hematological Neutrophils > 1.5 x 109/L Platelets > 100 x 109/L Renal Creatinine < 1.5 x ULN (Upper Limit Normal) Hepatic Bilirubin ≤ 1.0 X ULN Albumin ≥ 30g/L ALT ≤ 5.0 x ULN AST ≤ 5.0 x ULN LDH ≤ 2.5 x ULN The date of blood tests must be within 28 days prior to the time of randomisation.
- Age 18 years or older.
- Female patients must either be postmenopausal, sterile (surgically or radiation- or chemically-induced), or if sexually active using an acceptable method of contraception.
- Male patients must be surgically sterile or if sexually active and having a pre-menopausal partner must be using an acceptable method of contraception.
- Life expectancy of at least 3 months without any active treatment.
Who cannot join
- Evidence of ascites, cirrhosis, portal hypertension, main portal venous tumour involvement or thrombosis as determined by clinical or radiological assessment.
- More than 6 months since last chemotherapy administration before trial inclusion.
- Previous radiotherapy delivered to the upper abdomen.
- Non-malignant disease that would render the patient unsuitable for treatment according to this protocol.
- Prior major liver resection: remnant liver < 50% of the initial liver volume. Patient with a biliary stent can be included.
- Liver tumor involvement > 80% before study inclusion (not at diagnosis but when trial inclusion for the patient is planned).
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- Resectable metastatic disease at trial inclusion.
- Progressive disease during first-line metastatic chemotherapy. Adjuvant chemotherapy for colorectal cancer is not an exclusion criterion provided that it was completed more than 6 months prior to start of 1st line chemotherapy.
- No oxaliplatin or irinotecan use during the first 3 to 6 months induction chemotherapy.
- Pregnant or breast feeding.
- Concurrent or prior history of cancer other than adequately treated non melanoma skin cancer or carcinoma in situ of the cervix.
- Severe allergy to non-ionic contrast agents which would prevent contrast media use during the study.
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
Belgium10 sites, 7 recruiting
- Active, not recruiting
ASZ Aalst
Aalst, 9300
- Active, not recruiting
Institut Jules Bordet
Brussels, 1000
- Active, not recruiting
CUB Hôpital Erasme
Brussels, 1070
- Recruiting
University of St-Luc
Brussels, 1200
Marc Van den Eynde
- Recruiting
Grand Hôpital de Charleroi
Charleroi, 6000
Javier Carrasco, MD
- Recruiting
University of Antwerp
Edegem, Antwerp, 2650
Marc Peeters, MD, PhD
- Recruiting
ZOL Genk
Genk, 3600
Jaarke Vannoote, MD
- Not yet recruiting
AZ St-Lucas Gent
Ghent, 9000
Monique Troch, MD
- Recruiting
AZ Groeninge
Kortrijk, 8500
Philippe Vergauwe, MD
- Recruiting
CHU de Liège
Liège, 4000
Marc Polus, MD
About this study
Official title: A Randomised Phase III Trial Comparing Hepatic Arterial Injection of Yttrium-90 Resin Microspheres (SIR-spheres) Plus Systemic Maintenance Therapy Versus Systemic Maintenance Therapy Alone for Patients With Unresectable Liver Metastases From Colorectal Cancer Which Are Controlled After Induction Systemic Therapy
The investigators propose to conduct a randomised phase III trial evaluating a maintenance strategy comparing hepatic arterial injection of Yttrium-90 resin microspheres plus continuing simplified chemotherapy with/without targeted therapy versus continuing simplified chemotherapy with/without targeted therapy alone for patient with dominant or exclusive and unresectable liver mCRC controlled after 3-6 months of chemotherapy induction.
Read the detailed description
The aim of the study is to investigate whether an intensified maintenance treatment of SIRT + simplified maintenance chemotherapy has a benefit in terms of time to progression (TTP) compared to simplified chemotherapy maintenance alone, in patients with stable disease after 3-6 months induction therapy. We would like to demonstrate the feasibility and safety of this approach and to investigate if this strategy has the potential to increase the outcome of the patient.
Primary end-point:
- Time to first progression (TTP1 overall)
Secondary end-points:
- Time to global progression (TTP1 + TTP2), Time to second progression (TTP2), TTP1 liver only
- Progression Free Survival (PFS)
- Overall Survival (OS)
- Safety
- Ro resection rate
- Quality of Life
Exploratory analysis:
- Prediction and evaluation of SIR-spheres treatment response (only for Belgian centres)
- Conditions
- Colorectal Cancer
- Being tested
- HAI-90Y radioembolization (SIR-spheres injection), systemic chemotherapy LV5FU2
- Keywords
- TTP1, TTP2, PFS, Safety, R0 resection rate, Quality of life, Overall Survival
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HAI-90Y radioembolization (SIR-spheres injection)Device
Also called Sir-spheres microspheres, SIRT
Patients randomised to receive the combination of SIR-Spheres microspheres plus systemic chemotherapy LV5FU2 need to be assessed in order to determine their suitability for SIRT.
- Hepatic Angiogram
- Liver-Lung Break-Through Nuclear Scan
systemic chemotherapy LV5FU2Drug
Also called Leucovorin L, Levoleucovorin, 5-FU, 5-Fluoro-Uracil
Systemic chemotherapy with modified LV5FU2 will be administered according to the following regimen.
Cycle 1 onwards:
Day 1 Hour 0: Leucovorin L (levoleucovorin) 200 mg/m2 (or folinic acid 400 mg/m²) in 250 ml glucose 5%, 2-hour IV infusion Hour + 2: 5-FU bolus 400 mg/m2, IV bolus Hour + 2: 5-FU continuous infusion 2400 mg/m2, 46-hour cont. IV infusion Day 14 End of cycle. To be repeated every 14 days until evidence of treatment failure.
| Study group | Role | What they receive |
|---|---|---|
| A: systemic chemotherapy LV5FU2 alone | Active comparator | Modified LV5FU2 as described in protocol (6.2.1) D1-2 +/- bevacizumab or cetuximab or panitumumab (according its previous use) every 2 weeks Receives: Drug: systemic chemotherapy LV5FU2 |
| B:SIR-spheres+systemic chemotherapy LV5FU2 | Active comparator | ARM B: (Hepatic Arterial Infusion) HAI-90Y radioembolization (SIR-spheres injection) + modified LV5FU2 +/- bevacizumab or cetuximab or panitumumab according its previous use (refer to protocol). Receives: Device: HAI-90Y radioembolization (SIR-spheres injection) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to progression (TTP1 overall)
Time to first progression (TTP1 overall)
Measured: Up to 36 months
Secondary outcomes (6)
Time to global progression (TTP1 + TTP2)
- Time to global progression (TTP1 + TTP2), Time to second progression (TTP2), TTP1 liver only
Measured: Up to 42 months
PFS
Progression free survival
Measured: Up to 42 months
Safety
Measured: Up to 42 months
R0 resection rate
Measured: Up to 42 months
Quality of life
Using
- EORTC QLQ C30
- EQ-5D
Measured: Up to 42 months
Overall Survival (OS)
Measured: Up to 42 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jul 2013 (estimated)
- Study startAug 2013
- Primary completionDec 2017 (estimated)
- Study completionDec 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 162 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Universiteit Antwerpen
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Prof. Marc Peeters, Universiteit Antwerpen
- Investigators
- Marc Peeters, Study chair, Universiteit AntwerpenMarc Van den Eynde, Study chair, University of St-Luc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01895257
- Sponsor's protocol ID
- The SIR-step trial
- Other IDs
- 2012-000508-14
- Status last verified
- Jul 2017
- First submitted
- 6 Jun 2013
- Last updated
- 7 Jul 2017
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 7 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomised Phase III Trial Comparing Hepatic Arterial Injection of Yttrium-90 Resin Microspheres (SIR-spheres) Plus Systemic Maintenance Therapy Versus Systemic Maintenance Therapy Alone for Patients With Unresectable Liver Metastases From Colorectal Cancer Which Are Controlled After Induction Systemic Therapy
- ClinicalTrials.gov ID
- NCT01895257
- Acronym / sponsor ID
- The SIR-step trial
- Conditions
- Colorectal Cancer
- Keywords
- TTP1, TTP2, PFS, Safety, R0 resection rate, Quality of life, Overall Survival
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 162 participants (estimated)
- Lead sponsor
- Universiteit AntwerpenUniversity, hospital or other
- Study start
- Aug 2013
- Primary completion
- Dec 2017 (estimated)
- Study completion
- Dec 2018 (estimated)
- First posted
- 10 Jul 2013 (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.
The investigators propose to conduct a randomised phase III trial evaluating a maintenance strategy comparing hepatic arterial injection of Yttrium-90 resin microspheres plus continuing simplified chemotherapy with/without targeted therapy versus continuing simplified chemotherapy with/without targeted therapy alone for patient with dominant or exclusive and unresectable liver mCRC controlled after 3-6 months of chemotherapy induction.
Detailed description
The aim of the study is to investigate whether an intensified maintenance treatment of SIRT + simplified maintenance chemotherapy has a benefit in terms of time to progression (TTP) compared to simplified chemotherapy maintenance alone, in patients with stable disease after 3-6 months induction therapy. We would like to demonstrate the feasibility and safety of this approach and to investigate if this strategy has the potential to increase the outcome of the patient.
Primary end-point:
- Time to first progression (TTP1 overall)
Secondary end-points:
- Time to global progression (TTP1 + TTP2), Time to second progression (TTP2), TTP1 liver only
- Progression Free Survival (PFS)
- Overall Survival (OS)
- Safety
- Ro resection rate
- Quality of Life
Exploratory analysis:
- Prediction and evaluation of SIR-spheres treatment response (only for Belgian centres)
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| A: systemic chemotherapy LV5FU2 alone | Active comparator | Drug: systemic chemotherapy LV5FU2Modified LV5FU2 as described in protocol (6.2.1) D1-2 +/- bevacizumab or cetuximab or panitumumab (according its previous use) every 2 weeks |
| B:SIR-spheres+systemic chemotherapy LV5FU2 | Active comparator | Device: HAI-90Y radioembolization (SIR-spheres injection)ARM B: (Hepatic Arterial Infusion) HAI-90Y radioembolization (SIR-spheres injection) + modified LV5FU2 +/- bevacizumab or cetuximab or panitumumab according its previous use (refer to protocol). |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Willing and able to provide written informed consent
- Histologically confirmed adenocarcinoma of the colon or rectum, with or without primary tumour in situ. Unequivocal and measurable (RECIST 1.1) CT evidence of liver metastases which are not treatable by surgical resection and/or local ablation with curative intent at the time of trial entry.
- Partial response or stable disease (RECIST 1.1 criteria, controlled metastatic disease) after chemotherapy induction with oxaliplatin and/or irinotecan based induction chemotherapy (doublet or triplet combinations) +/- targeted therapies during 3 to 6 months.
- Trial inclusion must be performed between 3 and 6 months since the date of the first course of chemotherapy (induction) administration.
- Limited extra-hepatic metastases in the lung and/or lymph nodes are permitted. Metastases in the lung must either be not more than five nodules in number with no individual nodule more than 1 cm in diameter or 1 single lesion of up to 1.7 cm in diameter. Involvement of lymph nodes in 1 single anatomic region (pelvis, abdomen or chest) are permitted provided their longest diameter measures less than 2 cm.
Key exclusion criteria (12 listed)
- Evidence of ascites, cirrhosis, portal hypertension, main portal venous tumour involvement or thrombosis as determined by clinical or radiological assessment.
- More than 6 months since last chemotherapy administration before trial inclusion.
- Previous radiotherapy delivered to the upper abdomen.
- Non-malignant disease that would render the patient unsuitable for treatment according to this protocol.
- Prior major liver resection: remnant liver < 50% of the initial liver volume. Patient with a biliary stent can be included.
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 |
|---|---|---|
| HAI-90Y radioembolization (SIR-spheres injection)Also: Sir-spheres microspheres, SIRTPatients randomised to receive the combination of SIR-Spheres microspheres plus systemic chemotherapy LV5FU2 need to be assessed in order to determine their suitability for SIRT. 1. Hepatic Angiogram 2. Liver-Lung Break-Through Nuclear Scan | Device | B:SIR-spheres+systemic chemotherapy LV5FU2 |
| systemic chemotherapy LV5FU2Also: Leucovorin L, Levoleucovorin, 5-FU, 5-Fluoro-UracilSystemic chemotherapy with modified LV5FU2 will be administered according to the following regimen. Cycle 1 onwards: Day 1 Hour 0: Leucovorin L (levoleucovorin) 200 mg/m2 (or folinic acid 400 mg/m²) in 250 ml glucose 5%, 2-hour IV infusion Hour + 2: 5-FU bolus 400 mg/m2, IV bolus Hour + 2: 5-FU continuous infusion 2400 mg/m2, 46-hour cont. IV infusion Day 14 End of cycle. To be repeated every 14 days until evidence of treatment failure. | Drug | A: systemic chemotherapy LV5FU2 alone |
Primary outcome
Time to progression (TTP1 overall)
Time frame: Up to 36 months
Time to first progression (TTP1 overall)
6 secondary outcomes
Time to global progression (TTP1 + TTP2)
Time frame: Up to 42 months
PFS
Time frame: Up to 42 months
Safety
Time frame: Up to 42 months
R0 resection rate
Time frame: Up to 42 months
Quality of life
Time frame: Up to 42 months
Overall Survival (OS)
Time frame: Up to 42 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jul 2017.
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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.
Marc Peeters study chair
Universiteit Antwerpen
Marc Van den Eynde study chair
University of St-Luc
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing HAI-90Y radioembolization (SIR-spheres injection) and systemic chemotherapy LV5FU2 in people with Colorectal Cancer, run by Universiteit Antwerpen at 10 sites in Belgium.
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 15 inclusion and 12 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: status not confirmed, as of the sponsor's last update on 7 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Belgium. 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 phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Micheline Stempin (+32474074584, clinicaltrials@bgdo.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to progression (TTP1 overall) (time frame: Up to 36 months). 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 7 Jul 2017.