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NeuroblastomaPhase 2NCT01048086

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

A Phase 2 study testing Retinoic Acid in people with Neuroblastoma and Neuroendocrine Tumor, run by University of Iowa at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 6 months to 30 years
Conditions the study is for
Neuroblastoma, Neuroendocrine Tumor
What is being tested?
Retinoic Acid
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
0 participants
Where
1 siteUnited States
Study dates
Jun 2009to Nov 2013
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 6 months to 30 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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.
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  • 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
  • creatinine <1.0 for children <5 years of age; <1.2 for children 5-10 years of age; <1.7 for >10 years AND
  • GFR >80 mL/min/1.73 m2
  • urinalysis with no greater than 1+ hematuria or proteinuria
  • Cardiac function must be adequate
  • shortening fraction of > 28% by echo
  • ejection fraction > 50% by bi-plane method of echo
  • The effects of 90Y-DOTA-tyr3-Octreotide on the developing human fetus are unknown. Retinoic acid is known to be harmful to the developing human fetus. For these reasons and because Class C agents are known to be teratogenic, women and men of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
  • Ability to understand and the willingness to sign a written informed consent document.
  • Serum triglycerides <300 mg/dL.
  • Concomitant Therapy - The subject may not receive any other approved or investigational anti-neoplastic therapies for the treatment of the refractory somatostatin-receptor positive tumor during the course of the study, excluding somatostatin analogues and bisphosphonates. However, all subjects on somatostatin analogue therapy will discontinue therapy from 12 hours prior to a) injection with OctreoScan® or 111In-DOTA-tyr3-Octreotide, and b) infusion with 90Y-DOTA-tyr3-Octreotide until 12 hours post administration. Subjects who have been on hormonal therapy (other than somatostatin analogues) for > 2 months with SD or PD may continue to receive hormonal therapy during this study. Subjects who initiate another tumor-specific therapy will be discontinued from further treatment with 90YDOTA-tyr3-Octreotide. Disease progression alone does not mandate discontinuation of a subject from treatment.
  • All subjects who have received at least one dose of 90Y-DOTA-tyr3-Octreotide must continue into the Long-Term Follow-up Study Period at the point of treatment discontinuation. This is necessary to determine any long-term effects of treatment with 90Y-DOTA-tyr3-Octreotide. Subjects may receive, at the discretion of the investigator, appropriate medical treatment for medical problems that arise while on study.
  • Exclusion Criteria for enrollment and Cycle One study period:
  • 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.
  • Pregnant women are excluded from this study because 90Y-DOTA-tyr3-Octreotide is a Class C agent with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with 90Y-DOTA-tyr3-Octreotide, breastfeeding should be discontinued if the mother is treated with 90Y-DOTA-tyr3-Octreotide.
  • Because patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with 90Y-DOTA-tyr3-Octreotide. Appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated.

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Iowa Hospitals and Clinics

    Iowa City, Iowa, 52242

Other trials in United States

About this study

Official title: 90Y-DOTA-tyr3-Octreotide With or Without Retinoic Acid for the Treatment of Neuroblastoma and Neuroendocrine Tumors in Children and Young Adults. A Randomized, Placebo Controlled Phase II Trial With Dosimetry Guided Dosing

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.

Read the detailed description

This study builds on the promising results of the Phase I trial of 90Y-DOTA-tyr3-Octreotide in childhood solid tumors and the history of cis-Retinoic Acid (cis-RA) use in children with neuroblastoma. This study will combine these two agents in a randomized Phase II trial. The safety and feasibility of using individual dosimetry measurements to maximize the 90Y-DOTA-tyr3-Octreotide radiation dose to tumor while limiting the renal radiation dose to 23 Gy will be rigorously tested.

Fixed dosing will allow each subject to receive three cycles of 90Y-DOTA-tyr3-Octreotide at 50 mCi/m2. Dosimetry will be performed at each of these cycles; the combined dosimetry measurements will be utilized to determine whether or not a fourth cycle will be administered and, if so, what that dose will be. The administration of this additional cycle is conditional upon a) a subject not experiencing a dose-limiting toxicity during any previous cycle and b) meeting all criteria required at study initiation prior to the fourth dose.

Being tested
Retinoic Acid, Placebo
Keywords
neuroblastoma, neuroendocrine tumor, NET, retinoic acid
Medical subject headings
Neuroblastoma, Neuroendocrine Tumors

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Retinoic AcidDrug

    Also called 13-cis retinoic acid

    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.

  • PlaceboDrug

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

Study groups in NCT01048086
Study groupRoleWhat they receive
Retinoic AcidExperimentalNot described
Receives: Drug: Retinoic Acid
PlaceboPlacebo comparatorNot described
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 6 weeks after last treatment

Secondary outcomes (1)

  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.

    Measured: up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Jan 2010 (estimated)
  2. Study startJun 2009
  3. Primary completionNov 2013
  4. Study completionNov 2013

Why it stopped: No patients were enrolled because the company that pledged the drug does not yet have it available.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01048086
Sponsor's protocol ID
200904707
Status last verified
Jun 2016
First submitted
11 Jan 2010
Last updated
21 Jun 2016
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Retinoic Acid in people with Neuroblastoma and Neuroendocrine Tumor, run by University of Iowa at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 44 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 21 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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 (time frame: 6 weeks after last treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01048086.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Jun 2016.

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