Clinical trial NCT00049023: Radiolabeled Octreotide in Treating Children With Advanced or Refractory Solid Tumors
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Brain and Central Nervous System Tumors
Gastrointestinal Carcinoid Tumor
Islet Cell Tumor
Neuroblastoma
Pheochromocytoma
Sarcoma
Unspecified Childhood Solid Tumor, Protocol Specific
Keywords: 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
Lead sponsor: University of Iowa
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-01-27
Enrollment: 27
Sex: ALL
Minimum age (years): 2
Maximum age (years): 25
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Establish the three-cycle maximum-tolerated dose of 90Y-DOTA-tyr3-Octreotide
timeFrame: 6 weeks per cycle
measure: Evaluate the short term and long term safety (mild/moderate/severe/life-threatening adverse events, premature discontinuations and serious adverse events)
timeFrame: short term (6 weeks/cycle); long term (4-6 mos./cycle)
Secondary outcomes:
Other outcomes:
Locations:
city: Iowa City
country: United States
facility: Holden Comprehensive Cancer Center at University of Iowa
state: Iowa
Study officials:
affiliation: Holden Comprehensive Cancer Center
name: M. Sue O'Dorisio, MD, PhD
role: STUDY_CHAIR
References:
citation: 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.