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.

Condition	Treatment or Intervention	Phase
Lung Cancer Melanoma Lymphoma Brain Tumor Breast Cancer	Drug: octreotide  Drug: yttrium Y 90 SMT 487	Phase I

Further Study Details: 

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.

PROTOCOL 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.

Ages Eligible for Study:  18 Years and above

Criteria

PROTOCOL ENTRY 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: Brain; Endocrine; Pancreatic; Lymphoma; 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

--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

--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)

Florida
      H. Lee Moffitt Cancer Center and Research Institute, Tampa,  Florida,  33612-9497,  United States

Study chairs or principal investigators

Larry K. Kvols,  Study Chair,  H. Lee Moffitt Cancer Center and Research Institute   

Study ID Numbers:  CDR0000068241; MCC-12275; NCI-G00-1857; MCC-IRB-5473; NOVARTIS-SMT-B151
Record last reviewed:  March 2004
Last Updated:  October 13, 2004
Record first received:  October 4, 2000
ClinicalTrials.gov Identifier:  NCT00006368
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08