Neoplasms

All Conditions

Digestive System Diseases

Symptoms and General Pathology

Rare Diseases

Carcinoma

Carcinoma, Neuroendocrine

Colorectal Neoplasms

Adenocarcinoma

Intestinal Diseases

Colonic Diseases

Neoplasm Metastasis

Liver Diseases

Liver Neoplasms

Gastrointestinal Diseases

Neuroendocrine Tumors

Gastrointestinal Neoplasms

Intestinal Neoplasms

Neoplasms, Germ Cell and Embryonal

Digestive System Neoplasms

Rectal Diseases

Neoplasms, Nerve Tissue

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplastic Processes

Neuroendocrine Tumor

Neuroepithelioma

Hematinics

All Drugs and Chemicals

Herbal and Botanical

Liver Extracts

Cola

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.

TheraSphere, Yttrium-90 glass Microspheres

Jeff Geschwind, M.D.

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.

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

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 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.

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.

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 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 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.

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.

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.

Yale University

Professor of Radiology and Oncology

TheraSphere, Yttrium-90 glass Microspheres: 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

TheraSphere

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Jean-Francois Geschwind, MD

TheraSphere, Yttrium-90 glass Microspheres: Patients with unilobar disease will receive 120 ± 10% Gy (dose may be lower if clinically indicated) of TheraSphere to the affected lobe. Patients 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 tre

These data were not collected. See outcome measure #2.

Time to Progression (TTP) of the Treated Lesion(s) According to RECIST Criteria

Median PFS for all disease types

Median PFS for CRC

Median PFS for NE

Median PFS for non-CRC/non-NE

Median PFS for all subjects and stratified based on disease type.

Progression-free Survival (PFS) of the Treated Lesion(s) According to RECIST and EASL Criteria

TheraSphere, Yttrium-90 glass Microspheres: 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 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 lob

Analysis for TTP was not performed. In lieu of TTP, the PFS based on RECIST and EASL criteria was analyzed.

Time to Progression (TTP) of the Treated Lesion(s) According to EASL Criteria

All disease types

Colorectal cancer only

Neuroendocrine only

Non-CRC/Non-NE

RECIST for all applicable patients (n=43) were analyzed and also stratified based on disease type: CRC (n=9); NE (n=22); and non-CRC/non-NE (n=12).

Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST) v1.0

RECIST for all applicable patients (n=43) were analyzed and also stratified based on disease type: CRC (n=9); NE (n=22); and non-CRC/non-NE (n=12). 7 out of the 50 patients were not analyzed due to lack of follow-up imaging.

Tumor Response by the European Association for the Study of the Liver (EASL) Criteria

Median OS for all disease types

Median OS for CRC

Median OS for NE

Median OS for non-CRC/non-NE

Median OS for all patients (n=50) were analyzed and also stratified based on disease type: CRC (n=12); NE (n=26); and non-CRC/non-NE (n=12).

Overall Survival (OS)

OS rate for all patients

OS rate for tumor burden greater than 25%

OS rate for tumor burden 25% or less

2-year OS rate for all patients (n=50) were analyzed and also stratified based on tumor burden: Patients with tumor burden of 25% or less (n=34) and patients with tumor burden greater than 25% (n=16).

Overall Survival (OS) Rate at 2 Years

Elevated alkaline phosphatase

Elevated ALT

Elevated AST

Lymphocyte depression (asymptomatic)

Fatigue

Fever

Nausea

Heartburn

Vomiting

Pain

Decreased albumin

Elevated bilirubin

Anorexia

Weight loss

Constipation

Muscle pain

Cholecystitis

Death (disease progression)

Allergic reaction (contrast media)

Thrombosis/embolism (vascular access)

Liver failure

50 participants were assessed for adverse events, with a total of 207 adverse events reported. Two patients had grade 5 toxicities (grade 5 cholecystitis and death), which were attributed to disease progression and were not device-related.

Safety as Graded by CTCAE Version 3.0

Mean radiation dose for all patients

Mean dosing for CRC

Mean dosing for NE

Mean dosing for non-CRC/non-NE

Mean radiation doses were calculated for the total cohort of participants and also stratified according to disease type - colorectal cancer, neuroendocrine, and non-CRC/non-NE.

Mean Radiation Dose Delivered to Total Liver

Overall Study

Spots Global Cancer Trial Database for Intra-arterial Y-90 TheraSpheres for Hepatic Metastases From Solid Tumors

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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