90Y DOTA/Retinoic Acid for Neuroblastoma and Neuroendocrine Tumor (NET)

NCT01048086 | Withdrawn Phase 2 DMC

• 1 other identifier: 200904707
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This study is for patients with neuroblastoma or a neuroendocrine tumor who have not been able to have standard therapy or have failed the first-line therapy. The purpose of this study is to assess the safety and effectiveness of the combination of retinoic acid and Onalta (Y-90-DOTA-tyr3-Octreotide) in treating neuroblastoma and neuroendocrine tumors.

Conditions

Neuroblastoma; Neuroendocrine Tumor

Keywords

neuroblastoma; neuroendocrine tumor; NET; retinoic acid

Outcome Measures

Primary Outcomes (1)

• Evaluate tumor response to 90Y-DOTA-tyr3-Octreotide alone and in combination with 13-cis retinoic acid for the treatment of children and young adults with recurrent, somatostatin-receptor positive tumors

  6 weeks after last treatment

Secondary Outcomes (1)

• Estimate and compare time to tumor progression and overall survival in the patients treated with 90Y-DOTA-tyr3-Octreotide alone and in combination with 13-cis retinoic acid.

  up to 5 years

Study Arms (2)

Retinoic Acid

EXPERIMENTAL

Drug: Retinoic Acid

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Retinoic Acid DRUG

160 mg, given orally, divided BID on Days 1-4 of each cycle for 4 cycles. Each cycle will be six weeks in duration. Dose will be adjusted to 5.33 mg/kg/day divided BID for children \<12 kg.

Also known as: 13-cis retinoic acid

Retinoic Acid

Placebo DRUG

Placebo will be given in the same manner as retinoic acid in capsules that look identical.

Placebo

Eligibility Criteria

• Age: 6 Months - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Disease Criteria
• A pathologically confirmed (histology or cytology) malignant neoplasm that is determined to be neuroblastoma or neuroendocrine tumor. The subject's neoplastic disease must have been (positively) imaged by OctreoScan® or 111In-DOTA-tyr3-Octreotide within 4 weeks prior to ordering study drug.
• b) Disease not amenable to standard treatment (disease present after surgery and/or Sandostatin treatment) or subject has failed existing first line therapy (surgery and chemotherapy/radiation therapy).
• c) Upon baseline disease assessment, all subjects must have at least 1 measurable, evaluable, site of disease that either has never been irradiated or has been previously irradiated and has since demonstrated progression based on COG response criteria. Children's Oncology Group response criteria include: 1) Complete response (CR) is defined as no measureable disease; 2) partial response (PR) as \>50% decrease in longest X widest perpendicular diameter of target lesions with no increase in any lesions and no new lesions; 3) minor response (MR) as \>25%\<50% decrease in target lesions with no increase in any lesion and no new lesions; 4) stable disease as \<25% increase or decrease in any target lesion and no new lesions; 5) Progressive disease (PD) as an increase \>25% in any measureable lesion or the presence of any new lesion was considered progressive disease (PD). Response will be assessed based on intent to treat for all subjects who receive at least one dose of 90Y-DOTA-tyr3-Octreotide.
• Each subject must have at least one measurable somatostatin receptor positive lesion that has not had local irradiation via external beam, conformal or stereotactic radiation treatments within 4 weeks prior to study drug administration and no full craniospinal radiation within 3 months prior to study drug administration.
• Bone marrow with \>/= 40% cellularity or with 1 million CD34+ stem cells/kg stored.
• Life expectancy \> 2 months and \< 12 months.
• Biopsy of at least one lesion or bone marrow that has been identified as progressive malignancy within four weeks prior to the first dose of Onalta® is encouraged but not required. If no biopsy can be performed for clinical reasons, available tissue from a previous biopsy will be required.
• Age 6 months-30 years.
• COG performance status /= 60% or Lansky Play Scale \>/= 60%).
• Patients must have normal organ and marrow function as defined below:
• absolute neutrophil count \>1000/mm3
• platelets \>100,000/mm3
• total bilirubin \<1.5 x nl for age and weight
• AST(SGOT) \& ALT(SGPT) \<2.5 X institutional upper limit of normal for age

You may not qualify if:

• Age less than 6 months or greater than 30 years.
• Pregnancy or breast feeding.
• Surgery, radiation or chemotherapy within 4 weeks of study drug administration.
• Another investigational drug within 4 weeks of study drug administration.
• More than one, concurrent, malignant disease.
• History of congestive heart failure, unless cardiac ejection fraction ≥ 40%.
• Another significant medical, psychiatric, or surgical condition which is currently uncontrolled by treatment and which would likely affect the subject's ability to complete this protocol.
• Any subject for whom, in the opinion of their physician, a 24-hour discontinuation of somatostatin analogue therapy represents a health risk. Also subjects who have received long-acting somatostatin analogue in the past 21 days are excluded.
• Bone marrow cellularity \<40% without \>/= 1 million CD34+ stem cells/kg stored.
• External beam radiation to both kidneys (scatter doses of \< 500 cGy to a single kidney or radiation to \< 50% of a single kidney is acceptable).
• Antibodies to 90Y-DOTA-tyr3-Octreotide or Octreotide.
• Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) of study drug administration or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
• Patients may not be receiving any other investigational agents.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to 90YDOTA-tyr3-Octreotide.
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

Sponsors & Collaborators

• University of Iowa: lead
• Molecular Insight Pharmaceuticals, Inc.: collaborator

Study Sites (1)

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

MeSH Terms

Conditions

Neuroblastoma; Neuroendocrine Tumors

Interventions

Tretinoin; Isotretinoin

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Vitamin A; Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Diterpenes; Pigments, Biological; Biological Factors

Study Officials

• M Sue O'Dorisio, MD, PhD

  University of Iowa

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 11, 2010
• First Posted: January 13, 2010
• Study Start: June 1, 2009
• Primary Completion: November 1, 2013
• Study Completion: November 1, 2013
• Last Updated: June 21, 2016

Record last verified: 2016-06

Locations

US (1)