Intra-arterial Y-90 TheraSpheres for Hepatic Metastases From Solid Tumors
Condition: Liver Neoplasms
MeSH terms: Neoplasms; Neoplasm Metastasis; Liver Neoplasms
Intervention: TheraSphere, Yttrium-90 glass Microspheres
Intervention description: 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.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 50.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
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

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