Radiolabeled Octreotide in Treating Children With Advanced or Refractory Solid Tumors

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

Study Description

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.

Condition or disease	Intervention/treatment	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

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 27 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (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
• Study Start Date: January 2002
• Actual Primary Completion Date: August 2011
• Actual Study Completion Date: August 2011

Arms and Interventions

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 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

Outcome Measures

Primary Outcome Measures :

1. 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.
2. 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.

Eligibility Criteria

• Ages Eligible for Study: 2 Years to 25 Years (Child, Adult)
• Sexes Eligible for Study: All
• 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

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 of Results:

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.

• Responsible Party: O'Dorisio, M S, Professor, University of Iowa
• ClinicalTrials.gov Identifier: NCT00049023
• Other Study ID Numbers: 200008086; UIHC-200008086; NCI-V02-1710
• First Posted: January 27, 2003
• Last Update Posted: June 21, 2016
• Last Verified: June 2016

Keywords provided by O'Dorisio, M S, 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; Nervous System Neoplasms; Central Nervous System Neoplasms; Carcinoid Tumor; 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; Neoplasms by Site; Nervous System Diseases; Neuroendocrine Tumors; Adenocarcinoma; Carcinoma; Paraganglioma; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Adenoma; Pancreatic Neoplasms