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

NCT01177007 | Completed Phase 2 Results DMC

• 2 other identifiers: J09150, NA_00035790J09150
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (7)

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

  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

  12 months

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

  12 months

• Overall Survival (OS)

  Median follow-up time was 11.41 months (CI: 1.5-33.7)

• Overall Survival (OS) Rate at 2 Years

  Up to 2 years

Study Arms (1)

TheraSphere

EXPERIMENTAL

Device: TheraSphere, Yttrium-90 glass Microspheres

Interventions

TheraSphere, Yttrium-90 glass Microspheres DEVICE

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Yale University: lead

Study Sites (1)

Johns Hopkins Hospital

Baltimore, Maryland, 21287-4010, United States

Location

MeSH Terms

Conditions

Liver Neoplasms; 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; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases

Condition Hierarchy (Ancestors)

Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Jean-Francois Geschwind, MD
• Organization: Yale University

jeff.geschwind@yale.edu

203-785-5865

Study Officials

• Jeff Geschwind, M.D.

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Radiology and Oncology

Study Record Dates

• First Submitted: August 2, 2010
• First Posted: August 6, 2010
• Study Start: September 1, 2010
• Primary Completion: August 1, 2014
• Study Completion: August 1, 2014
• Last Updated: August 28, 2017
• Results First Posted: August 28, 2017

Record last verified: 2017-07

Locations

US (1)