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Radiolabeled Octreotide in Treating Children With Advanced or Refractory Solid Tumors

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ClinicalTrials.gov Identifier: NCT00049023
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : June 21, 2016
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
O'Dorisio, M S, University of Iowa

Tracking Information
First Submitted Date  ICMJE November 12, 2002
First Posted Date  ICMJE January 27, 2003
Last Update Posted Date June 21, 2016
Study Start Date  ICMJE January 2002
Actual Primary Completion Date August 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 17, 2016)
  • Establish the three-cycle maximum-tolerated dose of 90Y-DOTA-tyr3-Octreotide [ Time Frame: 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) [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00049023 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Radiolabeled Octreotide in Treating Children With Advanced or Refractory Solid Tumors
Official Title  ICMJE 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Brain and Central Nervous System Tumors
  • Gastrointestinal Carcinoid Tumor
  • Islet Cell Tumor
  • Neuroblastoma
  • Pheochromocytoma
  • Sarcoma
  • Unspecified Childhood Solid Tumor, Protocol Specific
Intervention  ICMJE Radiation: 90Y-DOTA-tyr3-OCTREOTIDE
Study Arms  ICMJE 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.
Intervention: Radiation: 90Y-DOTA-tyr3-OCTREOTIDE
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 17, 2016)
27
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE August 2011
Actual Primary Completion Date August 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 2 Years to 25 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00049023
Other Study ID Numbers  ICMJE 200008086
UIHC-200008086
NCI-V02-1710
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party O'Dorisio, M S, University of Iowa
Study Sponsor  ICMJE O'Dorisio, M S
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Study Chair: M. Sue O'Dorisio, MD, PhD Holden Comprehensive Cancer Center
PRS Account University of Iowa
Verification Date June 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP