Clinical trial NCT00006368: Yttrium Y 90 SMT 487 in Treating Patients With Refractory or Recurrent Cancer
Official title: A Phase I, Open-Label, Maximum Tolerated Single-Cycle and Four-Cycle Dose-Finding Study to Evaluation the Safety and Tolerability of 90Y-SMT 487 Administered by Intravenous Infusion to Subjects With Refractory Somatostatin-Receptor Positive Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Brain and Central Nervous System Tumors
Breast Cancer
Gastrointestinal Carcinoid Tumor
Islet Cell Tumor
Lung Cancer
Lymphoma
Melanoma (Skin)
Neoplastic Syndrome
Keywords: stage IV adult Hodgkin lymphoma
stage IV breast cancer
recurrent breast cancer
recurrent non-small cell lung cancer
recurrent adult Hodgkin lymphoma
extensive stage small cell lung cancer
recurrent small cell lung cancer
metastatic gastrointestinal carcinoid tumor
recurrent gastrointestinal carcinoid tumor
gastrinoma
recurrent adult brain tumor
insulinoma
recurrent islet cell carcinoma
ACTH-producing pituitary tumor
prolactin-producing pituitary tumor
growth hormone-producing pituitary tumor
recurrent pituitary tumor
TSH producing pituitary tumor
nonfunctioning pituitary tumor
adult brain stem glioma
adult craniopharyngioma
adult medulloblastoma
adult meningioma
adult glioblastoma
stage IV melanoma
recurrent melanoma
stage IV non-small cell lung cancer
WDHA syndrome
somatostatinoma
pancreatic polypeptide tumor
glucagonoma
pulmonary carcinoid tumor
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage IV grade 3 follicular lymphoma
stage IV adult diffuse small cleaved cell lymphoma
stage IV adult diffuse mixed cell lymphoma
stage IV adult diffuse large cell lymphoma
stage IV adult immunoblastic large cell lymphoma
stage IV adult lymphoblastic lymphoma
stage IV adult Burkitt lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent adult Burkitt lymphoma
adult anaplastic astrocytoma
adult myxopapillary ependymoma
adult anaplastic ependymoma
adult anaplastic oligodendroglioma
adult central nervous system germ cell tumor
adult pilocytic astrocytoma
adult subependymoma
adult ependymoblastoma
adult pineocytoma
adult pineoblastoma
adult meningeal hemangiopericytoma
stage IV mantle cell lymphoma
recurrent mantle cell lymphoma
adult choroid plexus tumor
recurrent marginal zone lymphoma
recurrent small lymphocytic lymphoma
stage IV small lymphocytic lymphoma
stage IV marginal zone lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
splenic marginal zone lymphoma
adult grade III meningioma
adult giant cell glioblastoma
adult gliosarcoma
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2004-04-02
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: Radiolabeled drugs such as yttrium Y 90 SMT 487 can locate tumor cells and deliver tumor-killing substances to them without harming normal cells.

PURPOSE: Phase I trial to study the effectiveness of yttrium Y 90 SMT 487 in treating patients who have refractory or recurrent cancer.

Detailed description: OBJECTIVES: I. Determine the maximum tolerated dose of yttrium Y 90-SMT 487 in patients with recurrent malignant neoplasms that prove positive for somatostatin receptors. II. Determine the safety and lifetime serious adverse event profile of this regimen in these patients. II. Determine the antitumor effect and the effect of repeated administrations on the renal excretion pharmacokinetics of this regimen in these patients.

OUTLINE: This is a dose escalation, multicenter study. Patients undergo octreotide scintigraphy to determine the location of somatostatin receptors. Patients then receive yttrium Y 90-SMT 487 IV over 15 minutes on day 1. Treatment continues every 6 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients each are entered on course I (vertical dose escalation) and courses II, III, and IV (horizontal dose escalation). Cohorts receive escalating doses of yttrium Y 90-SMT 487 until the maximum tolerated dose (MTD) is determined. MTDs are determined for a single course and for 4 courses. The MTD is defined as the dose preceding that at which no more than 2 of 6 patients experience dose limiting toxicities. Results of course I determine the dosage of subsequent courses. Patients are evaluated on days 2 and 7, and at weeks 4 and 6, following each injection of yttrium Y 90-SMT 487. Patients are followed at 12 and 18 months and then annually thereafter.

PROJECTED ACCRUAL: Approximately 20 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS: Histologically or cytologically confirmed, progressive malignant neoplasm Clinical diagnosis of multiple endocrine neoplasia (MEN) types I and II allowed Tumors positive for somatostatin receptors by octreotide scintigraphy, such as: Pituitary Brain Endocrine pancreatic Lymphoma Carcinoid Melanoma Small cell lung Breast Disease not amenable to standard treatment OR Failed existing first and second line therapies (failed at least 1 regimen in the case of small cell lung cancer) Bone disease (no diffuse bone marrow involvement), pleural effusions, and ascites allowed

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Course I: Karnofsky 50-100% Courses II-IV: Karnofsky 30-100% Life expectancy: At least 6 months and no greater than 2.5 years (for course I only) Hematopoietic: Course I: Hemoglobin at least 8 g/dL WBC at least 3,500/mm3 Platelet count at least 100,000/mm3 Courses II-IV: WBC at least 3,000/mm3 Platelet count at least 75,000/mm3 Hepatic: Not specified Renal: Creatinine no greater than 1.7 mg/dL OR Creatinine clearance at least 40 mL/min Cardiovascular: No history of congestive heart failure unless ejection fraction at least 40% Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 6 months after study No other concurrent malignancy except MEN I or II or squamous cell skin cancer No concurrent significant, uncontrolled, medical, psychiatric, or surgical condition that would preclude study (course 1)

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy Greater than 4 weeks since prior chemotherapy Endocrine therapy: At least 4 months since prior long acting somatostatin analogue Concurrent hormonal therapy (except somatostatin analogues) allowed if started at least 2 months previously Radiotherapy: Greater than 4 weeks since prior radiotherapy No prior radiotherapy to at least 25% of bone marrow Surgery: Greater than 4 weeks since prior surgery Other: Greater than 4 weeks since prior investigational drugs No other concurrent investigational drug therapy No other concurrent antineoplastic therapy Concurrent bisphosphonates allowed

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
Study officials:
affiliation: H. Lee Moffitt Cancer Center and Research Institute
name: Larry K. Kvols, MD
role: STUDY_CHAIR
References: