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

Primary Purpose

Neuroblastoma

Status

Completed

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

DFMO

Etoposide

About this trial

This is an interventional treatment trial for Neuroblastoma focused on measuring Refractory Neuroblastoma, Relapsed neuroblastoma

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Children's Hospital of Orange County
Connecticut Children's Hospital
Arnold Palmer Hospital for Children- MD Anderson
Helen DeVos Children's Hospital
Children's Mercy Hospitals and Clinics
Levine Children's Hospital
UVM/FAHC

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

DFMO and Etoposide

Arm Description

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

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.

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

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

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

Full Information

NCT ID

NCT01059071

First Posted

January 26, 2010

Last Updated

September 26, 2023

Sponsor

Giselle Sholler

Collaborators

Cancer Prevention Pharmaceuticals, Inc., University of Arizona, University of Hawaii

1. Study Identification

Unique Protocol Identification Number

NCT01059071

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Completed

Study Start Date

February 2010 (undefined)

Primary Completion Date

October 2014 (Actual)

Study Completion Date

May 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Giselle Sholler

Collaborators

Cancer Prevention Pharmaceuticals, Inc., University of Arizona, University of Hawaii

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Neuroblastoma

Keywords

Refractory Neuroblastoma, Relapsed neuroblastoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

21 (Actual)

8. Arms, Groups, and Interventions

Arm Title

DFMO and Etoposide

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

DFMO

Other Intervention Name(s)

Difluoromethylornithine

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Etoposide

Other Intervention Name(s)

Eposin, Etopophos, Vepesid, VP-16

Intervention Description

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.

Primary Outcome Measure Information:

Title

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

Description

Time Frame

length of study plus 30 days

Secondary Outcome Measure Information:

Title

Progression Free Survival (PFS)

Description

Time Frame

2 years

Title

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

Description

Time Frame

1 year

Title

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

Time Frame

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

Title

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

Time Frame

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

Title

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

Time Frame

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

10. Eligibility

Sex

All

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Giselle Sholler, MD

Organizational Affiliation

Beat Childhood Cancer at Atrium Health

Official's Role

Study Chair

Facility Information:

Facility Name

Children's Hospital of Orange County

City

Orange

State/Province

California

ZIP/Postal Code

92868

Country

United States

Facility Name

Connecticut Children's Hospital

City

Hartford

State/Province

Connecticut

ZIP/Postal Code

06106

Country

United States

Facility Name

Arnold Palmer Hospital for Children- MD Anderson

City

Orlando

State/Province

Florida

ZIP/Postal Code

32806

Country

United States

Facility Name

Helen DeVos Children's Hospital

City

Grand Rapids

State/Province

Michigan

ZIP/Postal Code

49503

Country

United States

Facility Name

Children's Mercy Hospitals and Clinics

City

Kansas City

State/Province

Missouri

ZIP/Postal Code

64108

Country

United States

Facility Name

Levine Children's Hospital

City

Charlotte

State/Province

North Carolina

ZIP/Postal Code

28204

Country

United States

Facility Name

UVM/FAHC

City

Burlington

State/Province

Vermont

ZIP/Postal Code

05401

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

26018967

Citation

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.

Results Reference

derived

Links:

URL

http://www.beatcc.org

Description

Beat Childhood Cancer Consortium website

Learn more about this trial

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

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