Radiolabeled Octreotide in Treating Children With Advanced or Refractory Solid Tumors

Sponsor

O'Dorisio, M S (Other)

Overall Status

Completed

CT.gov ID

NCT00049023

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Location

Arm

115

Duration (Months)

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 to study the safety and effectiveness of radiolabeled octreotide in treating children who have advanced or refractory solid tumors.

Condition or Disease	Intervention/Treatment	Phase
Brain and Central Nervous System Tumors Gastrointestinal Carcinoid Tumor Islet Cell Tumor Neuroblastoma Pheochromocytoma Sarcoma Unspecified Childhood Solid Tumor, Protocol Specific	Radiation: 90Y-DOTA-tyr3-OCTREOTIDE	Phase 1

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

27 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I, Open Label, Maximum Tolerated Dose-Finding Study to Evaluate the Safety and Tolerability of 90Y-DOTA-tyr3-Octreotide Administered by Intravenous Infusion to Children With Refractory Somatostatin-Receptor Positive Tumors

Study Start Date :

Jan 1, 2002

Actual Primary Completion Date :

Aug 1, 2011

Actual Study Completion Date :

Aug 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 90Y-DOTA-tyr3-OCTREOTIDE Dose escalation will proceed so that the single-cycle and three-cycle maximum tolerated doses of 90Y-DOTA-tyr3-Octreotide can be determined. The initial dose of 90Y-DOTA-tyr3-Octreotide to be administered is 30 mCi/m2 in each of three cycles. Dose escalation will proceed in 10 mCi/m2 intervals and will be permitted for the next cohort of subjects pending completion of Cycle 3 by 2 members of the previous cohort with no DLTs. A DLT is defined as a Grade 3 renal toxicity, Grade 4 bone marrow toxicity, or any other Grade 3 toxicity whether or not related to study drug and regardless of duration. Lymphopenia will not be used to define a DLT.	Radiation: 90Y-DOTA-tyr3-OCTREOTIDE

Arm

Intervention/Treatment

Experimental: 90Y-DOTA-tyr3-OCTREOTIDE

Dose escalation will proceed so that the single-cycle and three-cycle maximum tolerated doses of 90Y-DOTA-tyr3-Octreotide can be determined. The initial dose of 90Y-DOTA-tyr3-Octreotide to be administered is 30 mCi/m2 in each of three cycles. Dose escalation will proceed in 10 mCi/m2 intervals and will be permitted for the next cohort of subjects pending completion of Cycle 3 by 2 members of the previous cohort with no DLTs. A DLT is defined as a Grade 3 renal toxicity, Grade 4 bone marrow toxicity, or any other Grade 3 toxicity whether or not related to study drug and regardless of duration. Lymphopenia will not be used to define a DLT.

Radiation: 90Y-DOTA-tyr3-OCTREOTIDE

Outcome Measures

Primary Outcome Measures

Establish the three-cycle maximum-tolerated dose of 90Y-DOTA-tyr3-Octreotide [6 weeks per cycle]
Establish the three-cycle maximum-tolerated dose of 90Y-DOTA-tyr3-Octreotide administered by intravenous infusion to children with refractory somatostatin-receptor positive tumors based upon the 6 week/cycle dose-limiting-toxicity profile.
Evaluate the short term and long term safety (mild/moderate/severe/life-threatening adverse events, premature discontinuations and serious adverse events) [short term (6 weeks/cycle); long term (4-6 mos./cycle)]
2. Evaluate the short-term (6 weeks/cycle) and long term (4-6 months) safety (mild/moderate/severe/life-threatening adverse events, premature discontinuations and serious adverse events) serious adverse event profile of three-cycles of 90Y-DOTA-tyr3-Octreotide administered by intravenous infusion to children with refractory somatostatin-receptor positive tumors.

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Years to 25 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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/m^2

Cardiovascular

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

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 28 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