Liver NeoplasmsPhase 2NCT01177007
Intra-arterial Y-90 TheraSpheres for Hepatic Metastases From Solid Tumors
A Phase 2 study testing TheraSphere, Yttrium-90 glass Microspheres in people with Liver Neoplasms, run by Yale University at 1 site in United States.
Trial summary
This study is an open label prospective trial of TheraSphere treatment for patients who have liver metastases who have failed or are intolerant to other systemic or liver directed therapies. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Liver Neoplasms
- What is being tested?
- TheraSphere, Yttrium-90 glass Microspheres
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2010to Aug 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- 18 years of age or older,
- Patients with a diagnosis of metastatic disease to the liver who have failed or are intolerant to other systemic or liver directed therapies.
- A patient is considered to have failed to other systemic or liver-directed therapies when, in the opinion of the referring physician, the patient has progression of disease after receiving standard approved therapies. Specifically, if a patient has failed first line chemotherapy (or the standard approved therapies for that particular solid tumor), in the time period designed to assess that particular regimen (at least 30 days), then they may be enrolled into this protocol.
- A patient is intolerant to other systemic or liver-directed therapies when, in the opinion of the referring physician, for example, the patient is unable to tolerate appropriate chemotherapy, when the patient had residual toxicity from previous therapies (e.g. neuropathy from oxaliplatin), or when the patient's performance status is such that treatment with systemic therapies would result in excessive toxicity.
- Liver metastases are unresectable
- Target tumors should be measurable using standard imaging techniques
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- Tumor replacement ≤ 70% of total liver volume based on visual estimation by the Investigator
- Tumors are hypervascular based on visual estimation by the Investigator
- Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0-2
- At least one month has elapsed since most recent prior cancer therapy with the following exceptions
- Patients who are receiving Sandostatin for treatment of Neuroendocrine cancer may be enrolled and continue their Sandostatin treatment.
- Patients receiving anti-oestrogen therapy for breast cancer may continue their treatment if therapy was initiated greater than 30 days prior to TheraSphere treatment.
- Chemotherapy may continue if there is evidence of progression, in the liver, on treatment providing there is no change in the therapy in the 1 month prior to TheraSphere treatment and any immediate chemotherapeutic toxicity that will complicate TheraSphere treatment is resolved. In this case, the chemotherapy may continue because it is continuing to control the extrahepatic disease.
- Patient is willing to participate in the study and has signed the study informed consent
Who cannot join
- At risk of hepatic or renal failure, as indicated by any of the following pre-treatment laboratory and clinical findings within 28 days of treatment:
- Serum creatinine > 2.0 mg/dL, unless on dialysis
- Serum total bilirubin ≥ 2.0 mg/dL
- Albumin < 2.0 g/dL
- Any history of hepatic encephalopathy
- Contraindications to angiography and selective visceral catheterization that may include, but are not limited to, the following:
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- Any bleeding diathesis or coagulopathy that is not correctable by usual therapy or hemostatic agents (e.g., closure device)
- Severe peripheral vascular disease precluding catheterization
- History of severe allergy or intolerance to contrast agents, narcotics, sedatives or atropine that cannot be managed medically.
- Severe liver dysfunction or presentation of pulmonary insufficiency or a clinically evident history of chronic obstructive pulmonary disease
- Cirrhosis or portal hypertension
- Previous external beam radiation treatment to the liver
- Any intervention for, or compromise of the Ampulla of Vater
- Clinically evident ascites. (Note: A radiographic finding of trace ascites on imaging is acceptable).
- Any continuing complications of prior cancer therapy that have not improved or resolved prior to 21 days before the first treatment with TheraSphere (if the investigator determines that the continuing complication will compromise the safety of the patient following treatment with TheraSphere).
- In the judgment of the physician, significant life-threatening extrahepatic disease
- Concurrent enrollment in another clinical study
- Evidence on technetium-99m macroaggregated albumin (99mTc-MAA) scan that demonstrates lung shunting with a potential absorbed dose of radiation to the lungs >30 Gy. The 30 Gy limit is a cumulative limit over all infusions of TheraSphere.
- Evidence on technetium-99m macroaggregated albumin (99mTc-MAA) scan that demonstrates a potential for the deposition of microspheres to the gastrointestinal tract that cannot be corrected by placement of the catheter distal to collateral vessels or using standard angiographic techniques, such as coil embolization.
- A positive serum pregnancy test in women of childbearing potential
- In the Investigator's judgment, any co-morbid disease or condition or event (e.g., recent myocardial infarction) that would place the patient at undue risk, and that would preclude safe use of TheraSphere
Trial locations and contacts
1 site in 1 country.
United States1 site
Johns Hopkins Hospital
Baltimore, Maryland, 21287-4010
About this study
This study is an open label prospective trial of TheraSphere treatment for patients who have liver metastases who have failed or are intolerant to other systemic or liver directed therapies. Patients will be treated with TheraSphere at doses of 120 ± 10% Gy, and then followed for time to progression (TTP), safety, and overall survival.
- Conditions
- Liver Neoplasms
- Being tested
- TheraSphere, Yttrium-90 glass Microspheres
- Keywords
- Gastrointestinal Diseases, Colonic Diseases, Intestinal Diseases, Rectal Diseases, Neoplastic Processes, Pathologic Processes, Neuroendocrine Tumors, Neuroectodermal Tumors, Neoplasms, Germ Cell and Embryonal, Adenocarcinoma, Neoplasms, Nerve Tissue, Liver Diseases, Neoplasms, Carcinoma, Colorectal Neoplasms, Neoplasm Metastasis, Carcinoma, Neuroendocrine, Liver Neoplasms, Neoplasms, Glandular and Epithelial, Neoplasms by Histologic Type
- Medical subject headings
- Liver Neoplasms, Gastrointestinal Diseases, Colonic Diseases, Intestinal Diseases, Rectal Diseases, Neoplastic Processes, Pathologic Processes, Neuroendocrine Tumors
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TheraSphere, Yttrium-90 glass MicrospheresDevice
Patients with unilobar disease will receive 120 ± 10% Gy (dose may be lower if clinically indicated) of TheraSphere to the affected lobe. Patients presenting with bilobar disease will have their liver assessed and the lobe presenting the highest treatment priority will receive the first treatment of TheraSphere. Assigning priority of lobes to receive treatment is based on tumor bulk, associated clinical symptoms attributed to the tumor and technical/angiographic considerations. In patients with bilobar disease where the second lobe does not require immediate treatment, or in unilobar disease where tumors develop in the untreated lobe, additional TheraSphere treatment may be administered at any subsequent time. A treatment may consist of a single 120 ± 10% Gy infusion to a lobe, or, if angiography indicates the need, the 120 ± 10% Gy dose may be split into multiple infusions per lobe to ensure delivery of a total of 120 ± 10% Gy to each treated lobe.
| Study group | Role | What they receive |
|---|---|---|
| TheraSphere | Experimental | Not described Receives: Device: TheraSphere, Yttrium-90 glass Microspheres |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Progression (TTP) of the Treated Lesion(s) According to RECIST Criteria
This outcome was not assessed. Instead, the primary outcome of progression-free survival based on RECIST and EASL criteria was assessed and reported.
Measured: Evaluated 4 weeks following each TheraSpheres procedure, and at 2-3 month intervals thereafter.
Progression-free Survival (PFS) of the Treated Lesion(s) According to RECIST and EASL Criteria
Progression-free survival was defined as the time from the date of Y-90 radioembolization to date of disease progression or latest follow-up. PFS was analyzed via Kaplan-Meier methodology with log-rank test using all 50 patients on study and stratified based on disease type. RECIST and EASL criteria were used to assess progression with kappa value for intermethod agreement of treatment responses of 0.9.
Measured: 2 years
Secondary outcomes (7)
Time to Progression (TTP) of the Treated Lesion(s) According to EASL Criteria
This outcome was not assessed. Instead, the primary outcome of progression-free survival based on RECIST and EASL criteria was assessed and reported.
Measured: Evaluated 4 weeks following each TheraSpheres procedure, and at 2-3 month intervals thereafter.
Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST) v1.0
Efficacy as assessed by radiographic tumor response using RECIST criteria at baseline, at 4 weeks post treatment, and subsequent 3 month intervals.
Complete Response (CR): Disappearance of all lesions targeted by Y90 Partial Response (PR): At least 30% decrease in the sum of longest diameter (LD) of lesions targeted by Y90 Progressive Disease (PD): At least 20% increase in sum of LD of lesions targeted by Y90 Stable Disease (SD): Neither sufficient shrinkage for PR nor sufficient increase for PD.
Measured: 12 months
Tumor Response by the European Association for the Study of the Liver (EASL) Criteria
Efficacy as assessed by radiographic tumor response using EASL criteria at baseline up to 12 months post treatment.
Complete Response (CR): Achieving 100% tumor necrosis of targeted lesions Partial Response (PR): Demonstrating greater than 50% tumor necrosis in targeted lesions Progressive Disease (PD): Reappearance of or increased tumor enhancement greater than 25% in targeted lesions Stable Disease (SD): Not meeting requirements for CR or PR and not demonstrating evidence of progression in targeted lesions.
Measured: 12 months
Overall Survival (OS)
Measured from the date corresponding to initiation of therapy until the date of death due to any cause. At the time of registration, the outcome measure was entered in clinicaltrials.gov as "open-ended". Overall survival was analyzed via Kaplan-Meier methodology with log-rank test using all 50 patients on study and stratified based on disease type.
Measured: Median follow-up time was 11.41 months (CI: 1.5-33.7)
Overall Survival (OS) Rate at 2 Years
Measured from the date corresponding to initiation of therapy until the date of death due to any cause. At the time of registration, the outcome measure was entered in clinicaltrials.gov as "open-ended". At the time of results reporting, this outcome was presented as "Up to 2 years". Overall survival was analyzed via Kaplan-Meier methodology with log-rank test using all 50 patients on study and stratified based on disease type. 2-year OS rates were also stratified based on tumor burden.
Measured: Up to 2 years
Safety as Graded by CTCAE Version 3.0
Clinical and biochemical toxicity that were assessed as at least possibly related to treatment were recorded from the day of treatment until protocol exit or death. Toxicities were graded by the Common Terminology Criteria for Adverse Events (CTCAE) v3.0.
Measured: 12 months
Mean Radiation Dose Delivered to Total Liver
Therasphere dose calculation was performed using positron emission tomography-computed tomography (PET/CT) and single-photon emission computed tomography (SPECT) imaging post-procedure to estimate the actual delivered dose of Theraspheres to the liver.
Measured: 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Aug 2010 (estimated)
- Study startSep 2010
- Primary completionAug 2014
- Study completionAug 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Liver NeoplasmsStudies of the same condition, open and under way.
- More trials run by Yale UniversityThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Yale University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jeff Geschwind, Yale University
- Investigators
- Jeff Geschwind, M.D., Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01177007
- Sponsor's protocol ID
- J09150, NA_00035790
- Other IDs
- J09150
- Status last verified
- Jul 2017
- First submitted
- 2 Aug 2010
- Last updated
- 28 Aug 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intra-arterial Y-90 TheraSpheres for Hepatic Metastases From Solid Tumors
- ClinicalTrials.gov ID
- NCT01177007
- Acronym / sponsor ID
- J09150, NA_00035790
- Conditions
- Liver Neoplasms
- Keywords
- Gastrointestinal Diseases, Colonic Diseases, Intestinal Diseases, Rectal Diseases, Neoplastic Processes, Pathologic Processes, Neuroendocrine Tumors, Neuroectodermal Tumors
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Yale UniversityUniversity, hospital or other
- Study start
- Sep 2010
- Primary completion
- Aug 2014 (actual)
- Study completion
- Aug 2014 (actual)
- First posted
- 6 Aug 2010 (estimated)
- Results
- Posted 28 Aug 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is an open label prospective trial of TheraSphere treatment for patients who have liver metastases who have failed or are intolerant to other systemic or liver directed therapies. Patients will be treated with TheraSphere at doses of 120 ± 10% Gy, and then followed for time to progression (TTP), safety, and overall survival.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| TheraSphere | Experimental | Device: TheraSphere, Yttrium-90 glass Microspheres |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 18 years of age or older,
- Patients with a diagnosis of metastatic disease to the liver who have failed or are intolerant to other systemic or liver directed therapies.
- A patient is considered to have failed to other systemic or liver-directed therapies when, in the opinion of the referring physician, the patient has progression of disease after receiving standard approved therapies. Specifically, if a patient has failed first line chemotherapy (or the standard approved therapies for that particular solid tumor), in the time period designed to assess that particular regimen (at least 30 days), then they may be enrolled into this protocol.
- A patient is intolerant to other systemic or liver-directed therapies when, in the opinion of the referring physician, for example, the patient is unable to tolerate appropriate chemotherapy, when the patient had residual toxicity from previous therapies (e.g. neuropathy from oxaliplatin), or when the patient's performance status is such that treatment with systemic therapies would result in excessive toxicity.
- Liver metastases are unresectable
Key exclusion criteria (21 listed)
- At risk of hepatic or renal failure, as indicated by any of the following pre-treatment laboratory and clinical findings within 28 days of treatment:
- Contraindications to angiography and selective visceral catheterization that may include, but are not limited to, the following:
- Severe liver dysfunction or presentation of pulmonary insufficiency or a clinically evident history of chronic obstructive pulmonary disease
- Cirrhosis or portal hypertension
- Previous external beam radiation treatment to the liver
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 |
|---|---|---|
| TheraSphere, Yttrium-90 glass MicrospheresPatients with unilobar disease will receive 120 ± 10% Gy (dose may be lower if clinically indicated) of TheraSphere to the affected lobe. Patients presenting with bilobar disease will have their liver assessed and the lobe presenting the highest treatment priority will receive the first treatment of TheraSphere. Assigning priority of lobes to receive treatment is based on tumor bulk, associated clinical symptoms attributed to the tumor and technical/angiographic considerations. In patients with bilobar disease where the second lobe does not require immediate treatment, or in unilobar disease where tumors develop in the untreated lobe, additional TheraSphere treatment may be administered at any subsequent time. A treatment may consist of a single 120 ± 10% Gy infusion to a lobe, or, if angiography indicates the need, the 120 ± 10% Gy dose may be split into multiple infusions per lobe to ensure delivery of a total of 120 ± 10% Gy to each treated lobe. | Device | TheraSphere |
Primary outcome
Time to Progression (TTP) of the Treated Lesion(s) According to RECIST Criteria
Time frame: Evaluated 4 weeks following each TheraSpheres procedure, and at 2-3 month intervals thereafter.
This outcome was not assessed. Instead, the primary outcome of progression-free survival based on RECIST and EASL criteria was assessed and reported.
Progression-free Survival (PFS) of the Treated Lesion(s) According to RECIST and EASL Criteria
Time frame: 2 years
Progression-free survival was defined as the time from the date of Y-90 radioembolization to date of disease progression or latest follow-up. PFS was analyzed via Kaplan-Meier methodology with log-rank test using all 50 patients on study and stratified based on disease type. RECIST and EASL criteria were used to assess progression with kappa value for intermethod agreement of treatment responses of 0.9.
7 secondary outcomes
Time to Progression (TTP) of the Treated Lesion(s) According to EASL Criteria
Time frame: Evaluated 4 weeks following each TheraSpheres procedure, and at 2-3 month intervals thereafter.
Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST) v1.0
Time frame: 12 months
Tumor Response by the European Association for the Study of the Liver (EASL) Criteria
Time frame: 12 months
Overall Survival (OS)
Time frame: Median follow-up time was 11.41 months (CI: 1.5-33.7)
Overall Survival (OS) Rate at 2 Years
Time frame: Up to 2 years
Safety as Graded by CTCAE Version 3.0
Time frame: 12 months
Mean Radiation Dose Delivered to Total Liver
Time frame: 24 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Jeff Geschwind, M.D. principal investigator
Johns Hopkins University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing TheraSphere, Yttrium-90 glass Microspheres in people with Liver Neoplasms, run by Yale University 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 14 inclusion and 21 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: finished, as of the sponsor's last update on 28 Aug 2017. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Aug 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Time to Progression (TTP) of the Treated Lesion(s) According to RECIST Criteria (time frame: Evaluated 4 weeks following each TheraSpheres procedure, and at 2-3 month intervals thereafter.). The study lists 2 primary outcomes in all. 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 28 Aug 2017.