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

Neuroblastoma Clinical Trial

Official title:

A Phase I Trial for Refractory or Relapsed Neuroblastoma With DFMO Alone and in Combination With Etoposide

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01059071
• Other study ID #: NMTRC 002
• Status: Completed
• Phase: Phase 1
• Start date: February 2010
• Est. completion date: May 2015

Study information

• Verified date: April 2024
• Source: Milton S. Hershey Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: May 2015
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Neuroblastoma

Intervention

Drug:
• DFMO
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
• Etoposide
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.

Locations

Country	Name	City	State
United States	UVM/FAHC	Burlington	Vermont
United States	Levine Children's Hospital	Charlotte	North Carolina
United States	Helen DeVos Children's Hospital	Grand Rapids	Michigan
United States	Connecticut Children's Hospital	Hartford	Connecticut
United States	Children's Mercy Hospitals and Clinics	Kansas City	Missouri
United States	Children's Hospital of Orange County	Orange	California
United States	Arnold Palmer Hospital for Children- MD Anderson	Orlando	Florida

Sponsors (4)

Lead Sponsor	Collaborator
Giselle Sholler	Cancer Prevention Pharmaceuticals, Inc., University of Arizona, University of Hawaii

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Progression Free Survival (PFS)	Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions	2 years
Secondary	Number of Patients With an Overall Response Rate (ORR) of PR or CR	Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.	1 year
Secondary	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
Secondary	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
Secondary	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

External Links

•   Beat Childhood Cancer Consortium website