Radiolabeled Octreotide In Treating Children With Advanced Or Refractory Solid Tumors

Study Overview

Radiolabeled Octreotide in Treating Children With Advanced or Refractory Solid Tumors

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.

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.

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

200008086
UIHC-200008086
NCI-V02-1710

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2002-11-12	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2016-06-17
First Submitted that Met QC Criteria 2003-01-26	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ESTIMATED) 2016-06-21
First Posted (ESTIMATED) 2003-01-27	Results First Posted N/A	Last Verified 2016-06

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/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 escalat	RADIATION: 90Y-DOTA-tyr3-OCTREOTIDE

Participant Group/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 escalat

RADIATION: 90Y-DOTA-tyr3-OCTREOTIDE

Primary Outcome Measures	Measure Description	Time Frame
Establish the three-cycle maximum-tolerated dose of 90Y-DOTA-tyr3-Octreotide	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.	6 weeks per cycle
Evaluate the short term and long term safety (mild/moderate/severe/life-threatening adverse events, premature discontinuations and serious adverse events)	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.	short term (6 weeks/cycle); long term (4-6 mos./cycle)

Secondary Outcome Measures	Measure Description	Time Frame

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
2 Years

Accepts Healthy Volunteers:

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

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 participation

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 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

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 bisphosphonates
No concurrent combination antiretroviral therapy for HIV-positive patients

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

National Cancer Institute (NCI)

Investigators

STUDY_CHAIR: M. Sue O'Dorisio, MD, PhD, Holden Comprehensive Cancer Center

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Menda Y, O'Dorisio MS, Kao S, Khanna G, Michael S, Connolly M, Babich J, O'Dorisio T, Bushnell D, Madsen M. Phase I trial of 90Y-DOTATOC therapy in children and young adults with refractory solid tumors that express somatostatin receptors. J Nucl Med. 2010 Oct;51(10):1524-31. doi: 10.2967/jnumed.110.075226. Epub 2010 Sep 16.

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