Metastatic Colorectal CancerPhase 1LASERNCT02611661
Local Ablative Strategies After Endovascular Radioembolization
A Phase 1 study testing PET/MRI, Percutaneous ablation and Stereotactic body radiotherapy in people with Metastatic Colorectal Cancer, run by Washington University School of Medicine at 1 site in United States.
Trial summary
The rationale for this design is initial utilization of a standard-of-care therapy for mCRC (radioembolization) with a dose-calculation algorithm that has been verified as predictive for treatment response. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Colorectal Cancer
- What is being tested?
- PET/MRI, Percutaneous ablation and Stereotactic body radiotherapy
- Type of treatment
- Medical device, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Jan 2016to 13 Feb 2018
- Phase
- Phase 1
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of colorectal carcinoma with intrahepatic metastases; limited extrahepatic metastasis is allowed as long as the overall metastatic burden is hepatic dominant.
- Local surgical resection is not possible due to tumor or patient factors.
- Prior locoregional therapy is allowed if completed at least 2 weeks prior to enrollment.
- Prior chemotherapy is allowed if stopped/completed at least 2 weeks prior to enrollment.
- At least 18 years old.
- ECOG performance status ≤ 1.
- Scheduled to undergo radioembolization for treatment of intrahepatic metastases.
- Able to understand and willing to sign an IRB-approved written informed consent document.
Who cannot join
- Child-Pugh score 8 or greater.
- ALT or AST ≥ 6 x ULN.
- Prior history of abdominal irradiation. Patients who have received prior pelvic radiation for colorectal cancer are eligible; however, prior radiation treatment plans must be reviewed prior to enrollment.
- Presence of any contraindications to MRI scanning.
- GFR < 30 ml/min/1.73m2 (if receiving contrast for MRI).
- Currently on dialysis (if receiving contrast for MRI).
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- Prior allergic reaction to gadolinium-based contrast agents (if receiving contrast for MRI).
- Pregnant or nursing. Women of childbearing potential must have a negative pregnancy test within 14 days of study entry.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: Local Ablative Strategies After Endovascular Radioembolization (LASER)
The rationale for this design is initial utilization of a standard-of-care therapy for mCRC (radioembolization) with a dose-calculation algorithm that has been verified as predictive for treatment response. Prediction of treatment failure will enable the proposed subsequent locoregional therapies which were selected based on safety profiles and feasibility. While the goal of this study is assessing feasibility and safety of this approach, the end goal of improving overall patient outcomes by improved hepatic tumor control.
Read the detailed description
As the median time to radiographic response ranges from 3-8 months in published data, utilization of post-treatment PET/MRI dosimetry offers a powerful mechanism for immediate (within 36 hours) prediction of lesions that are likely to fail radioembolization. This early prediction enables a window for subsequent locoregional therapy prior to re-initiation of systemic chemotherapy. The investigators propose to evaluate patients who are undergoing radioembolization for mCRC using PET/MRI derived dosimetry obtained within 36 hours of the radioembolization procedure. Patients with four tumors or fewer receiving an average dose (Davg) less than 30 Gy will be candidates for subsequent locoregional therapy (stereotactic body radiotherapy (SBRT) or microwave ablation). This strategy will ideally increase the therapeutic index of locoregional therapies, particularly in the patient population who has exhausted their options for systemic therapy.
After radioembolization, patients will be divided into 5 strata as per the protocol schema. Patients who receive a Davg greater than 30 Gy in all hepatic lesions will be placed in Stratum 1 and will not undergo subsequent therapy. Patients with four or fewer lesions receiving a Davg less than 30 Gy will be placed in Strata 2, 3, or 4 based on distribution of the underdosed lesions. Stratum 2 will be comprised of patients with four or fewer underdosed lesions less than 3 cm which do not touch vasculature greater than 4 mm in size. Patients in this stratum will receive percutaneous microwave ablation to the underdosed lesions. Stratum 3 will be composed of patients with 4 or fewer underdosed lesions that are not amenable to microwave ablation by virtue of either size (greater than 3 cm) or proximity to hepatic vasculature greater than 4 mm in diameter. These patients will be treated with SBRT to the underdosed lesions. Patients with a combination of lesions some of which are amenable to microwave ablation and some of which are not (due to either size or proximity to vasculature) will be treated in Stratum 4 with a combined approach - microwave ablation to all lesions which are amenable and SBRT to any remaining underdosed lesions. Finally, Stratum 5 will consist of patients with more than 4 underdosed lesions or with disease progression; these patients will be referred for further systemic therapy and are not candidates for further locoregional therapy on study.
- Conditions
- Metastatic Colorectal Cancer
- Being tested
- PET/MRI, Percutaneous ablation, Stereotactic body radiotherapy
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PET/MRIDevice
Percutaneous ablationRadiation
Stereotactic body radiotherapyRadiation
Also called SBRT
| Study group | Role | What they receive |
|---|---|---|
| Stratum 1: Observe | Other | * PET/MRI within 36 hours of standard of care hepatic radioembolization received off study
* No further treatment just observation Receives: Device: PET/MRI |
| Stratum 2: Percutaneous ablation | Experimental | * PET/MRI within 36 hours of standard of care hepatic radioembolization received off study
* Percutaneous ablation can be radiofrequency ablation (RFA), microwave ablation (MWA), cryoablation, and irreversible electroporation Receives: Device: PET/MRI; Radiation: Percutaneous ablation |
| Stratum 3: SBRT | Experimental | * PET/MRI within 36 hours of standard of care hepatic radioembolization received off study
* The planned SBRT dose will be 30 Gy in 5 fractions of 6 Gy each. It is recommended that each fraction be separated by a minimum of 12 hours and a maximum of 8 days. Receives: Device: PET/MRI; Radiation: Stereotactic body radiotherapy |
| Stratum 4: SBRT + Percutaneous Ablation | Experimental | * PET/MRI within 36 hours of standard of care hepatic radioembolization received off study
* Percutaneous ablation can be radiofrequency ablation (RFA), microwave ablation (MWA), cryoablation, and irreversible electroporation
* The planned SBRT dose will be 30 Gy in 5 fractions of 6 Gy each. It is recommended that each fraction be separated by a minimum of 12 hours and a maximum of 8 days. Receives: Device: PET/MRI; Radiation: Percutaneous ablation; Radiation: Stereotactic body radiotherapy |
| Stratum 5: Referral for systemic therapy | No intervention | * PET/MRI within 36 hours of standard of care hepatic radioembolization received off study * Referred for further systemic therapy and are not candidates for further locoregional therapy on study. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and tolerability of administering hepatic locoregional therapy following radioembolization as measured by occurrences of grade 3 or higher toxicities of interest
- Strata 2, 3, and 4 only
- The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting.
Measured: 30 days after completion of therapy (approximately 6 weeks)
Secondary outcomes (4)
Late toxicity associated with radioembolization followed by dosimetry-guided subsequent hepatic locoregional therapy
-The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting.
Measured: Up to 6 months
Local recurrence rates associated with radioembolization followed by dosimetry-guided subsequent hepatic locoregional therapy
Measured: Up to 2 years
Overall survival rates associated with radioembolization followed by dosimetry-guided subsequent hepatic locoregional therapy
Measured: Up to 2 years
Response rates associated with radioembolization followed by dosimetry-guided subsequent hepatic locoregional therapy
- Complete Response (CR): Disappearance of all target lesions and non-target lesions. Normalization of tumor marker level.
- Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
- Progressive Disease (PD): At least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).
- Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Measured: Up to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Nov 2015 (estimated)
- Study start19 Jan 2016
- Primary completion13 Feb 2018
- Study completion13 Feb 2018
Why it stopped: Principal Investigator left the university.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Colorectal CancerStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Parag Parikh, M.D., Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02611661
- Sponsor's protocol ID
- 201511087
- Acronym
- LASER
- Status last verified
- Aug 2018
- First submitted
- 18 Nov 2015
- Last updated
- 16 Aug 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Local Ablative Strategies After Endovascular Radioembolization (LASER)
- ClinicalTrials.gov ID
- NCT02611661
- Acronym / sponsor ID
- LASER / 201511087
- Conditions
- Metastatic Colorectal Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Principal Investigator left the university.
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Study start
- 19 Jan 2016 (actual)
- Primary completion
- 13 Feb 2018 (actual)
- Study completion
- 13 Feb 2018 (actual)
- First posted
- 23 Nov 2015 (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 rationale for this design is initial utilization of a standard-of-care therapy for mCRC (radioembolization) with a dose-calculation algorithm that has been verified as predictive for treatment response. Prediction of treatment failure will enable the proposed subsequent locoregional therapies which were selected based on safety profiles and feasibility. While the goal of this study is assessing feasibility and safety of this approach, the end goal of improving overall patient outcomes by improved hepatic tumor control.
Detailed description
As the median time to radiographic response ranges from 3-8 months in published data, utilization of post-treatment PET/MRI dosimetry offers a powerful mechanism for immediate (within 36 hours) prediction of lesions that are likely to fail radioembolization. This early prediction enables a window for subsequent locoregional therapy prior to re-initiation of systemic chemotherapy. The investigators propose to evaluate patients who are undergoing radioembolization for mCRC using PET/MRI derived dosimetry obtained within 36 hours of the radioembolization procedure. Patients with four tumors or fewer receiving an average dose (Davg) less than 30 Gy will be candidates for subsequent locoregional therapy (stereotactic body radiotherapy (SBRT) or microwave ablation). This strategy will ideally increase the therapeutic index of locoregional therapies, particularly in the patient population who has exhausted their options for systemic therapy.
After radioembolization, patients will be divided into 5 strata as per the protocol schema. Patients who receive a Davg greater than 30 Gy in all hepatic lesions will be placed in Stratum 1 and will not undergo subsequent therapy. Patients with four or fewer lesions receiving a Davg less than 30 Gy will be placed in Strata 2, 3, or 4 based on distribution of the underdosed lesions. Stratum 2 will be comprised of patients with four or fewer underdosed lesions less than 3 cm which do not touch vasculature greater than 4 mm in size. Patients in this stratum will receive percutaneous microwave ablation to the underdosed lesions. Stratum 3 will be composed of patients with 4 or fewer underdosed lesions that are not amenable to microwave ablation by virtue of either size (greater than 3 cm) or proximity to hepatic vasculature greater than 4 mm in diameter. These patients will be treated with SBRT to the underdosed lesions. Patients with a combination of lesions some of which are amenable to microwave ablation and some of which are not (due to either size or proximity to vasculature) will be treated in Stratum 4 with a combined approach - microwave ablation to all lesions which are amenable and SBRT to any remaining underdosed lesions. Finally, Stratum 5 will consist of patients with more than 4 underdosed lesions or with disease progression; these patients will be referred for further systemic therapy and are not candidates for further locoregional therapy on study.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Stratum 1: Observe | Other | Device: PET/MRI* PET/MRI within 36 hours of standard of care hepatic radioembolization received off study * No further treatment just observation |
| Stratum 2: Percutaneous ablation | Experimental | Device: PET/MRI, Radiation: Percutaneous ablation* PET/MRI within 36 hours of standard of care hepatic radioembolization received off study * Percutaneous ablation can be radiofrequency ablation (RFA), microwave ablation (MWA), cryoablation, and irreversible electroporation |
| Stratum 3: SBRT | Experimental | Device: PET/MRI, Radiation: Stereotactic body radiotherapy* PET/MRI within 36 hours of standard of care hepatic radioembolization received off study * The planned SBRT dose will be 30 Gy in 5 fractions of 6 Gy each. It is recommended that each fraction be separated by a minimum of 12 hours and a maximum of 8 days. |
| Stratum 4: SBRT + Percutaneous Ablation | Experimental | Device: PET/MRI, Radiation: Percutaneous ablation, Radiation: Stereotactic body radiotherapy* PET/MRI within 36 hours of standard of care hepatic radioembolization received off study * Percutaneous ablation can be radiofrequency ablation (RFA), microwave ablation (MWA), cryoablation, and irreversible electroporation * The planned SBRT dose will be 30 Gy in 5 fractions of 6 Gy each. It is recommended that each fraction be separated by a minimum of 12 hours and a maximum of 8 days. |
| Stratum 5: Referral for systemic therapy | No intervention | –* PET/MRI within 36 hours of standard of care hepatic radioembolization received off study * Referred for further systemic therapy and are not candidates for further locoregional therapy on study. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Diagnosis of colorectal carcinoma with intrahepatic metastases; limited extrahepatic metastasis is allowed as long as the overall metastatic burden is hepatic dominant.
- Local surgical resection is not possible due to tumor or patient factors.
- Prior locoregional therapy is allowed if completed at least 2 weeks prior to enrollment.
- Prior chemotherapy is allowed if stopped/completed at least 2 weeks prior to enrollment.
- At least 18 years old.
Key exclusion criteria (9 listed)
- Child-Pugh score 8 or greater.
- ALT or AST ≥ 6 x ULN.
- Prior history of abdominal irradiation. Patients who have received prior pelvic radiation for colorectal cancer are eligible; however, prior radiation treatment plans must be reviewed prior to enrollment.
- Presence of any contraindications to MRI scanning.
- GFR < 30 ml/min/1.73m2 (if receiving contrast for MRI).
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 |
|---|---|---|
| PET/MRI | Device | Stratum 1: Observe, Stratum 2: Percutaneous ablation, Stratum 3: SBRT, Stratum 4: SBRT + Percutaneous Ablation |
| Percutaneous ablation | Radiation | Stratum 2: Percutaneous ablation, Stratum 4: SBRT + Percutaneous Ablation |
| Stereotactic body radiotherapyAlso: SBRT | Radiation | Stratum 3: SBRT, Stratum 4: SBRT + Percutaneous Ablation |
Primary outcome
Safety and tolerability of administering hepatic locoregional therapy following radioembolization as measured by occurrences of grade 3 or higher toxicities of interest
Time frame: 30 days after completion of therapy (approximately 6 weeks)
* Strata 2, 3, and 4 only * The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for all toxicity reporting.
4 secondary outcomes
Late toxicity associated with radioembolization followed by dosimetry-guided subsequent hepatic locoregional therapy
Time frame: Up to 6 months
Local recurrence rates associated with radioembolization followed by dosimetry-guided subsequent hepatic locoregional therapy
Time frame: Up to 2 years
Overall survival rates associated with radioembolization followed by dosimetry-guided subsequent hepatic locoregional therapy
Time frame: Up to 2 years
Response rates associated with radioembolization followed by dosimetry-guided subsequent hepatic locoregional therapy
Time frame: Up to 6 months
Results and safety
The study was stopped early (reason given: Principal Investigator left the university.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Aug 2018.
- Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of MedicineLink provided by the sponsor.
- Individual participant dataSharing planned: No
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CRC
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.
Parag Parikh, M.D. principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing PET/MRI, Percutaneous ablation and Stereotactic body radiotherapy in people with Metastatic Colorectal Cancer, run by Washington University School of Medicine at 1 site in United States.
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 8 inclusion and 9 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: stopped early, as of the sponsor's last update on 16 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Principal Investigator left the university.). Results are not available in the source record.
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?
Safety and tolerability of administering hepatic locoregional therapy following radioembolization as measured by occurrences of grade 3 or higher toxicities of interest (time frame: 30 days after completion of therapy (approximately 6 weeks)). 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 16 Aug 2018.