Carcinoma, Neuroendocrine, Colorectal Cancer, Neoplasm Metastasis
Conditions
Keywords
TheraSphere, radioactive microspheres, Yttrium-90, Yttrium glass microspheres
Brief summary
This study will evaluate Liver Progression Free Survival (PFS) and safety of TheraSphere treatment at doses of 120 Gy +/1 10% in patients at least 18 years of age diagnosed with metastatic disease to the liver that cannot be treated or is progressing following treatment with systemic or other liver-directed therapies.
Interventions
DEVICEYttrium 90 glass microspheres
120 Gy unilobar or bilobar infusion with the second infusion occurring 3-7 weeks following treatment of the first lobe
Sponsors
BTG International Inc.
Boston Scientific Corporation
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 18 years of age or older * diagnosis of metastatic disease to the liver that is refractory to, or inappropriate for, other systemic or liver-directed therapies * unresectable liver metastases * target tumors measurable using standard imaging techniques * tumor replacement \< or = 50% of total liver volume (visual estimation by investigator) * Hypervascular tumors (visual estimation by investigator) * Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2 * minimum one month since most recent prior cancer therapy with the exception of patients receiving Sandostatin for neuroendocrine cancer * patient informed consent
Exclusion criteria
* At risk of hepatic or renal failure within 21 days of treatment (serum creatinine \> 2.0 mg/dL unless on dialysis; serum bilirubin ≥ 2.0 mg/dL; albumin \< 2.0 mg/dL or any history of hepatic encephalopathy) * contraindications to angiography and selective visceral catheterization including any non-correctable bleeding diathesis or coagulopathy, severe peripheral vascular disease or history of non-management allergy or intolerance to contrast, narcotics, sedatives or atropine * severe liver dysfunction or presentation of pulmonary insufficiency or clinically evident history of chronic obstructive pulmonary disease * cirrhosis or portal hypertension * prior external beam radiation treatment to the liver * prior TheraSphere treatment to the liver * any intervention for, or compromise of the Ampulla of Vater * clinically evident ascites (trace ascites on imaging is acceptable) * any continuing complications of prior cancer therapy that have not improved or resolved prior to 21 days before first TheraSphere treatment * significant life-threatening extrahepatic disease in judgment of physician * concurrent enrollment in another study * alternative available therapies in judgement of physician * evidence on technetium-99m macroaggregated albumin scan that shows lung shunting \> 30 Gy cumulative limit * evidence on technetium-99m macroaggregated albumin scan showing potential for deposition of microspheres to the gastrointestinal tract that cannot be eliminated by catheter placement or corrective action using standard angiographic techniques * positive serum pregnancy test in women of childbearing potential * co-morbid disease or condition that puts the patient at undue risk or precludes use of TheraSphere in judgment of physician
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hepatic Progression-free Survival According to Response Evaluation Criterian in Solid Tumors (RECIST) | From the date of first treatment until date of first documented progression; median patient follow-up 30 months | Progression per RECIST v 1.0 is defined as at least 20% increase in the sum of the longest diameter of target lesions, taking as the reference the smallest sum of longest diameters recorded since treatment started, or unequivocal progression of existing non-target lesion or appearance of new lesions. A maximum of 5 target lesions per organ are assessed. To assess the impact of a non-systemic local therapy on progression, for the purposes of this trial, hepatic progression was defined as at least a 20% increase in the sum of the longest diameter of target hepatic lesions. Hepatic progression-free survival is the time from the day of first treatment with TheraSphere to determination of hepatic progression. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival | Time from first TheraSphere treatment to death; median follow up 30 months | Duration of survival from date of first TheraSphere treatment to date of death or censored to last known date alive. |
Countries
United States
Participant flow
Recruitment details
151 patients recruited from January 19, 2007 to October 7, 2009
Pre-assignment details
Patients were assigned to groups on the basis of type of primary cancer - colorectal cancer; neuroendocrine cancer or non-colorectal/non-neuroendocrine. Subjects who unable to receive TheraSphere (target dose 120 Gy) due to vascular shunting to the lungs or GI tract were not enrolled in the study and did not receive yttrium 90 glass microspheres.
Participants by arm
| Arm | Count |
|---|---|
| Colorectal Cancer colorectal cancer patients with liver metastatic disease, refractory to standard of care therapy | 61 |
| Neuroendocrine Cancer neuroendocrine cancer patients with liver metastatic disease, refractory to standard of care therapy | 43 |
| Non-Colorectal/Non-neuroendocrine patients with liver metastatic disease not arising from colorectal cancer or neuroendocrine cancer, refractory to standard of care therapy | 47 |
| Total | 151 |
Baseline characteristics
| Characteristic | Neuroendocrine Cancer | Non-Colorectal/Non-neuroendocrine | Colorectal Cancer | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 21 Participants | 27 Participants | 32 Participants | 80 Participants |
| Age, Categorical Between 18 and 65 years | 22 Participants | 20 Participants | 29 Participants | 71 Participants |
| Age, Continuous | 61.8 years STANDARD_DEVIATION 13.71 | 66.1 years STANDARD_DEVIATION 8.52 | 63.2 years STANDARD_DEVIATION 10.92 | 63.7 years STANDARD_DEVIATION 11.21 |
| Region of Enrollment United States | 43 participants | 47 participants | 61 participants | 151 participants |
| Sex: Female, Male Female | 19 Participants | 23 Participants | 25 Participants | 67 Participants |
| Sex: Female, Male Male | 24 Participants | 24 Participants | 36 Participants | 84 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 139 / 151 |
| serious Total, serious adverse events | 21 / 151 |
Outcome results
Primary
Hepatic Progression-free Survival According to Response Evaluation Criterian in Solid Tumors (RECIST)
Progression per RECIST v 1.0 is defined as at least 20% increase in the sum of the longest diameter of target lesions, taking as the reference the smallest sum of longest diameters recorded since treatment started, or unequivocal progression of existing non-target lesion or appearance of new lesions. A maximum of 5 target lesions per organ are assessed. To assess the impact of a non-systemic local therapy on progression, for the purposes of this trial, hepatic progression was defined as at least a 20% increase in the sum of the longest diameter of target hepatic lesions. Hepatic progression-free survival is the time from the day of first treatment with TheraSphere to determination of hepatic progression.
Time frame: From the date of first treatment until date of first documented progression; median patient follow-up 30 months
Population: Patients receiving at least one TheraSphere treatment with images evaluable by RECIST
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Colorectal Cancer | Hepatic Progression-free Survival According to Response Evaluation Criterian in Solid Tumors (RECIST) | 3.0 Months |
| Neuroendocrine Cancer | Hepatic Progression-free Survival According to Response Evaluation Criterian in Solid Tumors (RECIST) | 17.9 Months |
| Non-Colorectal/Non-neuroendocrine | Hepatic Progression-free Survival According to Response Evaluation Criterian in Solid Tumors (RECIST) | 2.9 Months |
| All Patients | Hepatic Progression-free Survival According to Response Evaluation Criterian in Solid Tumors (RECIST) | 3.4 Months |
Secondary
Overall Survival
Duration of survival from date of first TheraSphere treatment to date of death or censored to last known date alive.
Time frame: Time from first TheraSphere treatment to death; median follow up 30 months
Population: In the neuroendocrine group, a median overall survival was not achieved so a post-hoc analysis of 2 year survival was performed in Outcome Measure 3.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Colorectal Cancer | Overall Survival | 8.8 Months |
| Neuroendocrine Cancer | Overall Survival | 10.4 Months |
| Non-Colorectal/Non-neuroendocrine | Overall Survival | 13.6 Months |
Post Hoc
2 Year Survival
The percentage of patients in the neuroendocrine group alive at 2 years
Time frame: 24 months from treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Colorectal Cancer | 2 Year Survival | 79.1 percentage of treated subjects |