Clinical trial NCT01177007: Intra-arterial Y-90 TheraSpheres for Hepatic Metastases From Solid Tumors
Official title: Intra-arterial Y-90 TheraSpheres for Hepatic Metastases From Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Liver Neoplasms
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
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Lead sponsor: Yale University
Sponsor class: OTHER
First posted: 2010-08-06
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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. Patients will be treated with TheraSphere at doses of 120 ± 10% Gy, and then followed for time to progression (TTP), safety, and overall survival.


Eligibility criteria: 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

Primary outcomes:
measure: Time to Progression (TTP) of the Treated Lesion(s) According to RECIST Criteria
timeFrame: Evaluated 4 weeks following each TheraSpheres procedure, and at 2-3 month intervals thereafter.
measure: Progression-free Survival (PFS) of the Treated Lesion(s) According to RECIST and EASL Criteria
timeFrame: 2 years
Secondary outcomes:
measure: Time to Progression (TTP) of the Treated Lesion(s) According to EASL Criteria
timeFrame: Evaluated 4 weeks following each TheraSpheres procedure, and at 2-3 month intervals thereafter.
measure: Tumor Response by Response Evaluation Criteria in Solid Tumors (RECIST) v1.0
timeFrame: 12 months
measure: Tumor Response by the European Association for the Study of the Liver (EASL) Criteria
timeFrame: 12 months
measure: Overall Survival (OS)
timeFrame: Median follow-up time was 11.41 months (CI: 1.5-33.7)
measure: Overall Survival (OS) Rate at 2 Years
timeFrame: Up to 2 years
measure: Safety as Graded by CTCAE Version 3.0
timeFrame: 12 months
measure: Mean Radiation Dose Delivered to Total Liver
timeFrame: 24 hours
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
Study officials:
affiliation: Johns Hopkins University
name: Jeff Geschwind, M.D.
role: PRINCIPAL_INVESTIGATOR
References: