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Trial record 17 of 531 for:    "Neuroblastoma"

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

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ClinicalTrials.gov Identifier: NCT01059071
Recruitment Status : Completed
First Posted : January 29, 2010
Results First Posted : June 20, 2016
Last Update Posted : October 2, 2018
Sponsor:
Collaborators:
Cancer Prevention Pharmaceuticals, Inc.
University of Arizona
University of Hawaii
Information provided by (Responsible Party):
Giselle Sholler, Spectrum Health Hospitals

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Neuroblastoma
Interventions Drug: DFMO
Drug: Etoposide
Enrollment 21

Recruitment Details  
Pre-assignment Details  
Arm/Group Title 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
Hide Arm/Group Description

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

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.

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 2: 750 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.

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 3:1000 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.

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 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.

Period Title: Overall Study
Started 4 5 3 9
Completed 2 1 1 3
Not Completed 2 4 2 6
Reason Not Completed
Lack of Efficacy             1             4             2             3
Withdrawal by Subject             1             0             0             2
Physician Decision             0             0             0             1
Arm/Group Title DFMO and Etoposide
Hide Arm/Group Description

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.

Overall Number of Baseline Participants 21
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 21 participants
8.75
(1 to 17)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 21 participants
Female
7
  33.3%
Male
14
  66.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 21 participants
Hispanic or Latino
3
  14.3%
Not Hispanic or Latino
16
  76.2%
Unknown or Not Reported
2
   9.5%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 21 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
2
   9.5%
White
17
  81.0%
More than one race
0
   0.0%
Unknown or Not Reported
2
   9.5%
1.Primary Outcome
Title Number of Participants With Adverse Events as a Measure of Safety and Tolerability
Hide Description 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
Time Frame length of study plus 30 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Received at least one dose of DFMO
Arm/Group Title 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
Hide Arm/Group Description:

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

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.

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 2: 750 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.

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 3:1000 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.

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 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.

Overall Number of Participants Analyzed 4 5 3 9
Measure Type: Number
Unit of Measure: participants
2 4 0 5
2.Secondary Outcome
Title Progression Free Survival (PFS)
Hide Description 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
Time Frame 2 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
18 subjects out of the 21 enrolled were evaluable. 3 subjects did not make it to an evaluable time point.
Arm/Group Title DFMO and Etoposide
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 18
Median (95% Confidence Interval)
Unit of Measure: Days
85
(62 to 418)
3.Secondary Outcome
Title Number of Patients With an Overall Response Rate (ORR) of PR or CR
Hide Description 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.
Time Frame 1 year
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
18 subjects out of the 21 enrolled were evaluable. 3 subjects did not make it to an evaluable time point.
Arm/Group Title DFMO and Etoposide
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 18
Measure Type: Number
Unit of Measure: participants
4
4.Secondary Outcome
Title Tmax of DFMO in Pediatrics Using Pharmacokinetic (PK) Testing.
Hide Description [Not Specified]
Time Frame Cycle 1 Day 8 at hour 0 (pre-dose), 30 minutes, 1 hour, 3 hours, and 6 hours
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Cohort at max dose of 1500mg/m2 BID
Arm/Group Title DFMO and Etoposide
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 9
Mean (Standard Deviation)
Unit of Measure: hours
2.88  (1.45)
5.Secondary Outcome
Title Cmax of DFMO in Pediatrics Using Pharmacokinetic (PK) Testing.
Hide Description [Not Specified]
Time Frame Cycle 1 Day 8 at hour 0 (pre-dose), 30 minutes, 1 hour, 3 hours, and 6 hours
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Cohort at max dose of 1500mg/m2 BID
Arm/Group Title DFMO and Etoposide
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 9
Mean (Standard Deviation)
Unit of Measure: mcg/ml
28.89  (14.96)
6.Secondary Outcome
Title AUC of DFMO in Pediatrics Using Pharmacokinetic (PK) Testing.
Hide Description [Not Specified]
Time Frame Cycle 1 Day 8 at hour 0 (pre-dose), 30 minutes, 1 hour, 3 hours, and 6 hours
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Cohort at max dose of 1500mg/m2 BID
Arm/Group Title DFMO and Etoposide
Hide Arm/Group Description:

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.

Overall Number of Participants Analyzed 9
Mean (Standard Deviation)
Unit of Measure: (mcg/ml) * hr
108.38  (53.23)
Time Frame New adverse events collected from first dose of study drug to 30 days past last dose of study drug. Related adverse events followed until resolution.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title DFMO and Etoposide
Hide Arm/Group Description

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.

All-Cause Mortality
DFMO and Etoposide
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
DFMO and Etoposide
Affected / at Risk (%) # Events
Total   3/21 (14.29%)    
Musculoskeletal and connective tissue disorders   
Pain * 1 [1]  1/21 (4.76%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Progression of Disease resulting in death * 1  2/21 (9.52%)  2
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, CTCAE (3.0)
[1]
Back Pain unrelated to study drug.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
DFMO and Etoposide
Affected / at Risk (%) # Events
Total   11/21 (52.38%)    
Blood and lymphatic system disorders   
Anemia * 1  4/21 (19.05%)  8
Neutorpenia * 1  5/21 (23.81%)  9
Thrombocytopenia * 1  1/21 (4.76%)  5
Leukopenia * 1  1/21 (4.76%)  1
GGT elevation * 1  1/21 (4.76%)  1
Hypoalbuminemia * 1  1/21 (4.76%)  1
Hypophosphatemia * 1  1/21 (4.76%)  1
Eye disorders   
Conjunctivitis * 1  1/21 (4.76%)  1
Gastrointestinal disorders   
Constipation * 1  2/21 (9.52%)  2
Diarrhea * 1  1/21 (4.76%)  1
Mouth pain * 1  1/21 (4.76%)  1
Nausea * 1  1/21 (4.76%)  1
vomiting * 1  1/21 (4.76%)  1
General disorders   
Anorexia * 1  1/21 (4.76%)  1
Pain * 1  1/21 (4.76%)  1
Sleep disturbance * 1  1/21 (4.76%)  1
Hepatobiliary disorders   
ALT elevation * 1  2/21 (9.52%)  2
AST elevation * 1  3/21 (14.29%)  3
Nervous system disorders   
Neuropathy * 1  1/21 (4.76%)  1
Renal and urinary disorders   
urinary retention * 1  1/21 (4.76%)  1
Respiratory, thoracic and mediastinal disorders   
Infection, sinus * 1  1/21 (4.76%)  1
Skin and subcutaneous tissue disorders   
Rash * 1  1/21 (4.76%)  1
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, CTCAE (3.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Giselle Sholler, MD
Organization: NMTRC
Phone: 6162670335
Responsible Party: Giselle Sholler, Spectrum Health Hospitals
ClinicalTrials.gov Identifier: NCT01059071     History of Changes
Other Study ID Numbers: NMTRC 002
First Submitted: January 26, 2010
First Posted: January 29, 2010
Results First Submitted: May 11, 2016
Results First Posted: June 20, 2016
Last Update Posted: October 2, 2018