Radiolabeled Octreotide in Treating Children With Advanced or Refractory Solid Tumors

Sarcoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00049023
• Other study ID #: 200008086
• Secondary ID: UIHC-200008086NC
• Status: Completed
• Phase: Phase 1
• First received: November 12, 2002
• Last updated: June 17, 2016
• Start date: January 2002
• Est. completion date: August 2011

Study information

• Verified date: June 2016
• Source: University of Iowa
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: August 2011
• Est. primary completion date: August 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years to 25 Years

Eligibility

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

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain and Central Nervous System Tumors
• Carcinoid Tumor
• Central Nervous System Neoplasms
• Gastrointestinal Carcinoid Tumor
• Gastrointestinal Neoplasms
• Islet Cell Tumor
• Malignant Carcinoid Syndrome
• Neoplasms
• Nervous System Neoplasms
• Neuroblastoma
• Neuroendocrine Tumors
• Pheochromocytoma
• Sarcoma
• Unspecified Childhood Solid Tumor, Protocol Specific

Intervention

Radiation:
• 90Y-DOTA-tyr3-OCTREOTIDE

Locations

Country	Name	City	State
United States	Holden Comprehensive Cancer Center at University of Iowa	Iowa City	Iowa

Sponsors (2)

Lead Sponsor	Collaborator
O'Dorisio, M S	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. 201 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Primary	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)	Yes