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Radiolabeled Octreotide in Treating Children With Advanced or Refractory Solid Tumors

This study has been completed.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
O'Dorisio, M S, University of Iowa
ClinicalTrials.gov Identifier:
NCT00049023
First received: November 12, 2002
Last updated: June 17, 2016
Last verified: June 2016
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by University of Iowa:

Primary Outcome Measures:
  • Establish the three-cycle maximum-tolerated dose of 90Y-DOTA-tyr3-Octreotide [ Time Frame: 6 weeks per cycle ] [ Designated as safety issue: Yes ]
    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) ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 27
Study Start Date: January 2002
Study Completion Date: August 2011
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   2 Years to 25 Years   (Child, Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00049023

Locations
United States, Iowa
Holden Comprehensive Cancer Center at University of Iowa
Iowa City, Iowa, United States, 52242-1002
Sponsors and Collaborators
O'Dorisio, M S
National Cancer Institute (NCI)
Investigators
Study Chair: M. Sue O'Dorisio, MD, PhD Holden Comprehensive Cancer Center
  More Information

Publications:
Responsible Party: O'Dorisio, M S, Professor, University of Iowa
ClinicalTrials.gov Identifier: NCT00049023     History of Changes
Other Study ID Numbers: 200008086  UIHC-200008086  NCI-V02-1710 
Study First Received: November 12, 2002
Last Updated: June 17, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Iowa:
childhood grade III meningioma
disseminated neuroblastoma
localized unresectable neuroblastoma
metastatic pheochromocytoma
metastatic Ewing sarcoma/peripheral primitive neuroectodermal tumor
recurrent childhood brain tumor
recurrent childhood medulloblastoma
recurrent neuroblastoma
recurrent pheochromocytoma
recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor
regional neuroblastoma
regional pheochromocytoma
unspecified childhood solid tumor, protocol specific
recurrent childhood ependymoma
childhood infratentorial ependymoma
childhood supratentorial ependymoma
recurrent islet cell carcinoma
gastrinoma
insulinoma
metastatic gastrointestinal carcinoid tumor
recurrent gastrointestinal carcinoid tumor
regional gastrointestinal carcinoid tumor

Additional relevant MeSH terms:
Neoplasms
Sarcoma
Neuroblastoma
Carcinoid Tumor
Neuroendocrine Tumors
Nervous System Neoplasms
Central Nervous System Neoplasms
Pheochromocytoma
Malignant Carcinoid Syndrome
Gastrointestinal Neoplasms
Adenoma, Islet Cell
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Adenocarcinoma
Carcinoma
Neoplasms by Site
Nervous System Diseases
Paraganglioma
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Adenoma
Pancreatic Neoplasms

ClinicalTrials.gov processed this record on December 02, 2016