Radiolabeled Octreotide in Treating Children With Advanced or Refractory Solid Tumors

NCT ID: NCT00049023

Last Updated: 2016-06-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-01-31
• Study Completion Date: 2011-08-31

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.

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.

Conditions

Brain and Central Nervous System Tumors; Gastrointestinal Carcinoid Tumor; Islet Cell Tumor; Neuroblastoma; Pheochromocytoma; Sarcoma; Unspecified Childhood Solid Tumor, Protocol Specific

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

90Y-DOTA-tyr3-OCTREOTIDE

Intervention Type: RADIATION

Interventions

90Y-DOTA-tyr3-OCTREOTIDE

Intervention Type: RADIATION

Eligibility Criteria

Inclusion 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/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

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 25 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

O'Dorisio, M S

OTHER

Sponsor Role: lead

Responsible Party

O'Dorisio, M S

Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

M. Sue O'Dorisio, MD, PhD

Role: STUDY_CHAIR

Holden Comprehensive Cancer Center

Locations

Holden Comprehensive Cancer Center at University of Iowa

Iowa City, Iowa, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 20847174 (View on PubMed)

Other Identifiers

UIHC-200008086

Identifier Type: -

Identifier Source: secondary_id

NCI-V02-1710

Identifier Type: -

Identifier Source: secondary_id

200008086

Identifier Type: -

Identifier Source: org_study_id