Safety Study for Refractory or Relapsed Neuroblastoma With DFMO Alone and in Combination With Etoposide

NCT01059071 | Completed Phase 1 Results DMC

• 1 other identifier: NMTRC 002
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 7

Brief Summary

The purpose of this research study is to evaluate a new investigational drug to treat neuroblastoma. This study drug is called DFMO. The objectives of this study will be to monitor for safety and to find a maximum tolerated dose in this population. A secondary objective will be to look at efficacy of DFMO. The safety of the proposed dosing regimen in this trial will be tested by an on-going risk/benefit assessment during the study. A patient benefiting from treatment, not progressing on therapy, and in the absence of any safety issues associated with DFMO and/or etoposide may continue on treatment with the expectation that there will be an overall clinical benefit. The procedures involved in this study include Medical history, Physical exam, Vital signs (blood pressure, pulse, temperature), Blood tests, Urine tests, MRI or CT scan of the tumor(s), MIBG scans, and Bone marrow aspirations. All of these tests and procedures are considered standard of care for this population. Drug administration is also part of this protocol, including an investigational new drug called DFMO, and later combined with an already approved drug, etoposide. The proposed dosing regimen is an oral dose of DFMO two times a day for each day while on study. There will be 5 cycles. Each cycle will be 21 days in length. The first cycle will be DFMO alone. In the second cycle etoposide will be added in and will be given orally once a day for the first 14 days of each cycle (cycles 2-5).

Conditions

Neuroblastoma

Keywords

Refractory Neuroblastoma; Relapsed neuroblastoma

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Adverse Events as a Measure of Safety and Tolerability

  To determine the safety, tolerability and maximum tolerated dose (MTD) of DFMO as a single agent and in combination with etoposide in pediatric and young adult patients with refractory or recurrent neuroblastoma

  length of study plus 30 days

Secondary Outcomes (5)

• Progression Free Survival (PFS)

  2 years

• Number of Patients With an Overall Response Rate (ORR) of PR or CR

  1 year

• Tmax of DFMO in Pediatrics Using Pharmacokinetic (PK) Testing.

  Cycle 1 Day 8 at hour 0 (pre-dose), 30 minutes, 1 hour, 3 hours, and 6 hours

• Cmax of DFMO in Pediatrics Using Pharmacokinetic (PK) Testing.

  Cycle 1 Day 8 at hour 0 (pre-dose), 30 minutes, 1 hour, 3 hours, and 6 hours

• AUC of DFMO in Pediatrics Using Pharmacokinetic (PK) Testing.

  Cycle 1 Day 8 at hour 0 (pre-dose), 30 minutes, 1 hour, 3 hours, and 6 hours

Study Arms (1)

DFMO and Etoposide

EXPERIMENTAL

Drug: DFMO; Drug: Etoposide

Interventions

DFMO DRUG

Escalating doses of DFMO in a 3 +3 cohort design. DFMO at current cohort Dose Level orally each day for 21 day cycles Dose level 1: 500 mg/m2 PO BID Dose level 2: 750 mg/m2 PO BID Dose level 3:1000 mg/m2 PO BID Dose level 4:1500 mg/m2 PO BID

Also known as: Difluoromethylornithine

DFMO and Etoposide

Etoposide DRUG

Starting with Cycle 2, etoposide will be given at 50mg/m2/dose PO daily for the first 14 days of each 21 day cycle. Capsules will be rounded to closest 50 mg.

Also known as: Eposin, Etopophos, Vepesid, VP-16

DFMO and Etoposide

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age: 0-21 years at the time of diagnosis.
• Diagnosis: Histologic verification at either the time of original diagnosis or relapse of neuroblastoma.
• Disease Status: Refractory or relapsed neuroblastoma
• Measurable disease, including at least one of the following:
• Measurable tumor \>10mm by CT or MRI A positive MIBG and abnormal urinary catecholamine levels Positive bone marrow biopsy/aspirate.
• Current disease state must be one for which there is currently no known curative therapy.
• A negative urine pregnancy test is required for female subjects of child bearing potential (onset of menses or ≥13 years of age).
• Patients without bone marrow metastases must have an ANC \> 500/μl and platelet count \>50,000/μl
• Organ Function Requirements Subjects must have adequate liver function as defined by AST or ALT \<10x normal Serum bilirubin must be ≤ 2.0 mg/dl Serum creatinine must be ≥ 1.5 mg/dl
• Informed Consent: All subjects and/or legal guardians must sign informed written consent. Assent, when appropriate, will be obtained according to institutional guidelines

You may not qualify if:

• Life expectancy \<2 months or Lansky score \<30%
• Investigational Drugs: Subjects who are currently receiving another investigational drug are excluded from participation.
• Anti-cancer Agents: Subjects who are currently receiving other anticancer agents are not eligible. Subjects must have fully recovered from the effects of prior chemotherapy (hematological and bone marrow suppression effects)
• Infection: Subjects who have an uncontrolled infection are not eligible until the infection is judged to be well controlled in the opinion of the investigator.
• Subjects who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study, or in whom compliance is likely to be suboptimal, should be excluded.

Sponsors & Collaborators

• Giselle Sholler: lead
• Cancer Prevention Pharmaceuticals, Inc.: collaborator
• University of Arizona: collaborator
• University of Hawaii: collaborator

Study Sites (7)

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

Connecticut Children's Hospital

Hartford, Connecticut, 06106, United States

Location

Arnold Palmer Hospital for Children- MD Anderson

Orlando, Florida, 32806, United States

Location

Helen DeVos Children's Hospital

Grand Rapids, Michigan, 49503, United States

Location

Children's Mercy Hospitals and Clinics

Kansas City, Missouri, 64108, United States

Location

Levine Children's Hospital

Charlotte, North Carolina, 28204, United States

Location

UVM/FAHC

Burlington, Vermont, 05401, United States

Location

Related Publications (1)

• Saulnier Sholler GL, Gerner EW, Bergendahl G, MacArthur RB, VanderWerff A, Ashikaga T, Bond JP, Ferguson W, Roberts W, Wada RK, Eslin D, Kraveka JM, Kaplan J, Mitchell D, Parikh NS, Neville K, Sender L, Higgins T, Kawakita M, Hiramatsu K, Moriya SS, Bachmann AS. A Phase I Trial of DFMO Targeting Polyamine Addiction in Patients with Relapsed/Refractory Neuroblastoma. PLoS One. 2015 May 27;10(5):e0127246. doi: 10.1371/journal.pone.0127246. eCollection 2015.

  PMID: 26018967 DERIVED

Related Links

• Beat Childhood Cancer Consortium website

MeSH Terms

Conditions

Neuroblastoma

Interventions

Eflornithine; Etoposide; etoposide phosphate

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)

Ornithine; Amino Acids, Basic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Diamino; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Results Point of Contact

• Title: Giselle Sholler, MD
• Organization: NMTRC

giselle.sholler@helendevoschildrens.org

6162670335

Study Officials

• Giselle Sholler, MD

  Beat Childhood Cancer at Atrium Health

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Beat Childhood Cancer Chair

Study Record Dates

• First Submitted: January 26, 2010
• First Posted: January 29, 2010
• Study Start: February 1, 2010
• Primary Completion: October 1, 2014
• Study Completion: May 1, 2015
• Last Updated: August 6, 2024
• Results First Posted: June 20, 2016

Record last verified: 2024-08

Locations

US (7)