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.
- 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.
- Histologically or cytologically confirmed malignant neoplasm
- Not amenable to standard therapy or has failed existing first- and second-line
- 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
- 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
- 2 to 25
- COG 0-2 OR
- Karnofsky 60-100% OR
- Lansky 60-100%
- 2-12 months
- See Disease Characteristics
- Absolute neutrophil count at least 1,000/mm^3
- Platelet count at least 100,000/mm^3
- Bilirubin less than 1.5 times normal
- AST and ALT less than 2.5 times upper limit of normal
- 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/m^2
- Shortening fraction at least 28% 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
- 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
PRIOR CONCURRENT THERAPY:
- Not specified
- At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
- More than 28 days since prior long-acting somatostatin analogues
- No concurrent somatostatin analogues 12 hours before or 12 hours after study drug
- Concurrent hormonal therapy (other than somatostatin analogue) allowed provided
patient received hormonal therapy for at least 2 months and has stable disease or
- 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)
- At least 4 weeks since prior surgery
- Recovered from prior therapy
- At least 4 weeks since prior investigational drugs
- No other concurrent approved or investigational anti-neoplastic therapies except for
- No concurrent combination antiretroviral therapy for HIV-positive patients