RATIONALE: Radiolabeled octreotide can locate tumor cells and deliver radioactive tumor-killing substances to them without harming normal cells.

PURPOSE: This phase I trial is studying the effectiveness of radiolabeled octreotide in treating children who have advanced or refractory solid tumors.

Condition	Treatment or Intervention	Phase
Ewing's family of tumors adult solid tumor childhood brain tumor childhood solid tumor Gastrointestinal Cancer Neuroblastoma	Drug: yttrium Y 90-DOTA-tyr3-octreotide  Procedure: endocrine therapy  Procedure: hormone therapy  Procedure: somatostatin analogue therapy	Phase I

Further Study Details: 

OBJECTIVES:

• Determine the maximum tolerated dose of yttrium Y 90-DOTA-tyr3-octreotide in children with advanced or refractory somatostatin receptor-positive tumors.
• Determine the short-term and long-term safety and the serious adverse-event profiles of this drug in these patients.
• Determine any potential antitumor effect of this drug in these patients.
• Correlate level of somatostatin receptor type 2 expression with response in patients treated with this drug.

OUTLINE: This is a dose-escalation study.

Patients receive yttrium Y 90-DOTA-tyr3-octreotide IV over 5-10 minutes on day 1. Treatment repeats every 6 weeks for up to 3 courses in the absence of unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of yttrium Y 90-DOTA-tyr3-octreotide until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 6 patients experience dose-limiting toxicity.

Patients are followed weekly after each treatment course, 6 weeks after the last course, and then every 6 months thereafter for life.

PROJECTED ACCRUAL: Approximately 25-35 patients will be accrued for this study.

Ages Eligible for Study:  2 Years   -   25 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically or cytologically confirmed malignant neoplasm
• Not amenable to standard therapy or has failed existing first- and second-line therapies
• Tumor positive for somatostatin receptors by OctreoScan within the past 4 weeks
• At least 1 measurable lesion
• Lesions that have been previously irradiated must demonstrate progression since radiation
• At least 1 measurable somatostatin receptor-positive lesion that has not been irradiated within the past 4 weeks AND has not had full craniospinal radiation within the past 3 months
• Bone marrow with at least 40% cellularity OR at least 20% cellularity with one million CD34+ stem cells/kg stored
• No diffuse bone marrow involvement by OctreoScan scintigraphy

PATIENT CHARACTERISTICS: Age

• 2 to 25

Performance status

• COG 0-2 OR
• Karnofsky 60-100% OR
• Lansky 60-100%

Life expectancy

• 2-12 months

Hematopoietic

• See Disease Characteristics
• Absolute neutrophil count at least 1,000/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• Bilirubin less than 1.5 times normal
• AST and ALT less than 2.5 times upper limit of normal

Renal

• Creatinine no greater than 1 mg/dL (children less than 5 years of age)
• Creatinine less than 1.2 mg/dL (children 5 to 10 years of age)
• Creatinine less than 1.7 mg/dL (children over 10 years of age) AND
• Glomerular filtration rate at least 80 mL/min

Cardiovascular

• Shortening fraction at least 24% by echocardiogram
• Ejection fraction at least 50% by bi-plane method of echocardiogram
• No prior congestive heart failure unless ejection fraction at least 40%
• No unstable angina pectoris
• No cardiac arrhythmia
• No symptomatic congestive heart failure

Other

• No other concurrent malignancy
• No other significant uncontrolled medical, psychiatric, or surgical condition that would preclude study compliance
• No antibodies to yttrium Y 90-DOTA-tyr3-octreotide or octreotide
• No prior allergic reactions to compounds of similar chemical or biologic composition to yttrium Y 90-DOTA-tyr3-octreotide
• No ongoing or active infection
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception during and for 6 months after study participation

PRIOR CONCURRENT THERAPY: Biologic therapy

• Not specified

Chemotherapy

• At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)

Endocrine therapy

• More than 42 days since prior long-acting somatostatin analogues
• No concurrent somatostatin analogues 12 hours before or 12 hours after study drug administration
• Concurrent hormonal therapy (other than somatostatin analogue) allowed provided patient received hormonal therapy for at least 2 months and has stable disease or progressive disease

Radiotherapy

• See Disease Characteristics
• At least 4 weeks since prior radiotherapy
• No prior radiotherapy to 25% or more of bone marrow
• No prior external beam radiotherapy to both kidneys (scatter doses of less than 500 cGy to a single kidney or radiation to less than 50% of a single kidney is allowed)

Surgery

• At least 4 weeks since prior surgery

Other

• Recovered from prior therapy
• At least 4 weeks since prior investigational drugs
• No other concurrent approved or investigational anti-neoplastic therapies except for bisphosphonates
• No concurrent combination antiretroviral therapy for HIV-positive patients

Iowa
      Holden Comprehensive Cancer Center at University of Iowa, Iowa City,  Iowa,  52242-1009,  United States; Recruiting

Study chairs or principal investigators

M. Sue O'Dorisio, MD, PhD,  Study Chair,  Holden Comprehensive Cancer Center   

Study ID Numbers:  CDR0000257582; UIHC-200008086; NCI-V02-1710; NCT00049023
Record last reviewed:  December 2004
Last Updated:  January 7, 2005
Record first received:  November 12, 2002
ClinicalTrials.gov Identifier:  NCT00049023
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08