Intra-arterial Y-90 TheraSpheres for Hepatic Metastases From Solid Tumors

Study Overview
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Brief Summary
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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.

Official Title
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Intra-arterial Y-90 TheraSpheres for Hepatic Metastases From Solid Tumors

Conditions
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Liver Neoplasms

Intervention / Treatment
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* Device: TheraSphere, Yttrium-90 glass Microspheres


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria 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 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 Exclusion Criteria 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: 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TheraSphere<br> | Device: TheraSphere, Yttrium-90 glass Microspheres<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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. | 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. | 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. | 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. | 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. | 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. | 24 hours | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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, Intestinal Neoplasms, Gastrointestinal Neoplasms, Digestive System Neoplasms, Neoplasms by Site, Digestive System Diseases