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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


Phase 1
2 Years
25 Years
Open (Enrolling)
Both
Brain and Central Nervous System Tumors, Gastrointestinal Carcinoid Tumor, Islet Cell Tumor, Neuroblastoma, Pheochromocytoma, Sarcoma, Unspecified Childhood Solid Tumor, Protocol Specific

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Trial Information

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


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.

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

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Principal Investigator

M. Sue O'Dorisio, MD, PhD

Investigator Role:

Study Chair

Investigator Affiliation:

Holden Comprehensive Cancer Center

Authority:

Unspecified

Study ID:

CDR0000257582

NCT ID:

NCT00049023

Start Date:

January 2002

Completion Date:

Related Keywords:

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

Name

Location

Holden Comprehensive Cancer Center at University of IowaIowa City, Iowa  52242-1002