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ch14.18 Pharmacokinetic Study in High-risk Neuroblastoma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
United Therapeutics
ClinicalTrials.gov Identifier:
NCT01592045
First received: April 30, 2012
Last updated: August 20, 2015
Last verified: August 2015
Results First Received: June 3, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Pharmacokinetics Study;   Intervention Model: Crossover Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Neuroblastoma
Interventions: Biological: ch14.18 -NCI
Biological: ch14.18-UTC
Biological: Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF)
Biological: Aldesleukin (IL-2)
Drug: Isotretinoin

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Sequence 1

UTC ch14.18 for two courses followed by NCI ch14.18 for three courses

ch14.18 -NCI: 25 mg/m^2/day IV for four consecutive days

ch14.18-UTC: 17.5 mg/m^2/day IV for four consecutive days

Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF): GM-CSF will be administered SC at a dose of 250 mcg/m^2/day for 14 days during Courses 1, 3, and 5.

Aldesleukin (IL-2): Aldesleukin (IL-2) will be administered IV at a dose of 3 MIU/m^2/day for the first week and at a dose of 4.5 MIU/m^2/day for the second week during Courses 2 and 4.

Isotretinoin: Isotretinoin (13-cis-retinoic acid; ISOT) will be administered by mouth over six courses as follows:

If weight > 12 kg: 80 mg/m^2/dose twice daily (total daily dose is 160 mg/m^2/day, divided twice daily).

If weight ≤ 12 kg: 2.67 mg/kg/dose twice daily (total daily dose is 5.33 mg/kg/day, divided twice daily).

Sequence 2

NCI ch14.18 for two courses followed by UTC ch14.18 for three courses

ch14.18 -NCI: 25 mg/m^2/day IV for four consecutive days

ch14.18-UTC: 17.5 mg/m^2/day IV for four consecutive days

Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF): GM-CSF will be administered SC at a dose of 250 mcg/m^2/day for 14 days during Courses 1, 3, and 5.

Aldesleukin (IL-2): Aldesleukin (IL-2) will be administered IV at a dose of 3 MIU/m^2/day for the first week and at a dose of 4.5 MIU/m^2/day for the second week during Courses 2 and 4.

Isotretinoin: Isotretinoin (13-cis-retinoic acid; ISOT) will be administered by mouth over six courses as follows:

If weight > 12 kg: 80 mg/m^2/dose twice daily (total daily dose is 160 mg/m^2/day, divided twice daily).

If weight ≤ 12 kg: 2.67 mg/kg/dose twice daily (total daily dose is 5.33 mg/kg/day, divided twice daily).


Participant Flow:   Overall Study
    Sequence 1   Sequence 2
STARTED   14   14 
Completed Course 1   13   14 
Completed Course 2   13   13 
Completed Course 3   11   13 
Completed Course 4   11   12 
Completed Course 5   9   12 
COMPLETED   9   12 
NOT COMPLETED   5   2 
Disease Progression                1                1 
Adverse Event                1                1 
Withdrawal by Subject                1                0 
Moved out of country                2                0 



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Twenty-eight subjects were enrolled in this study with all subjects receiving at least one dose of study therapy.

Reporting Groups
  Description
Sequence 1

UTC ch14.18 for two courses followed by NCI ch14.18 for three courses

ch14.18 -NCI: 25 mg/m^2/day IV for four consecutive days

ch14.18-UTC: 17.5 mg/m^2/day IV for four consecutive days

Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF): GM-CSF will be administered SC at a dose of 250 mcg/m^2/day for 14 days during Courses 1, 3, and 5.

Aldesleukin (IL-2): Aldesleukin (IL-2) will be administered IV at a dose of 3 MIU/m^2/day for the first week and at a dose of 4.5 MIU/m^2/day for the second week during Courses 2 and 4.

Isotretinoin: Isotretinoin (13-cis-retinoic acid; ISOT) will be administered by mouth over six courses as follows:

If weight > 12 kg: 80 mg/m^2/dose twice daily (total daily dose is 160 mg/m^2/day, divided twice daily).

If weight ≤ 12 kg: 2.67 mg/kg/dose twice daily (total daily dose is 5.33 mg/kg/day, divided twice daily).

Sequence 2

NCI ch14.18 for two courses followed by UTC ch14.18 for three courses

ch14.18 -NCI: 25 mg/m^2/day IV for four consecutive days

ch14.18-UTC: 17.5 mg/m^2/day IV for four consecutive days

Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF): GM-CSF will be administered SC at a dose of 250 mcg/m^2/day for 14 days during Courses 1, 3, and 5.

Aldesleukin (IL-2): Aldesleukin (IL-2) will be administered IV at a dose of 3 MIU/m^2/day for the first week and at a dose of 4.5 MIU/m^2/day for the second week during Courses 2 and 4.

Isotretinoin: Isotretinoin (13-cis-retinoic acid; ISOT) will be administered by mouth over six courses as follows:

If weight > 12 kg: 80 mg/m^2/dose twice daily (total daily dose is 160 mg/m^2/day, divided twice daily).

If weight ≤ 12 kg: 2.67 mg/kg/dose twice daily (total daily dose is 5.33 mg/kg/day, divided twice daily).

Total Total of all reporting groups

Baseline Measures
   Sequence 1   Sequence 2   Total 
Overall Participants Analyzed 
[Units: Participants]
 14   14   28 
Age 
[Units: Years]
Mean (Full Range)
 4 
 (2 to 7) 
 4 
 (1 to 9) 
 4 
 (1 to 9) 
Gender 
[Units: Participants]
     
Female   6   6   12 
Male   8   8   16 
Ethnicity (NIH/OMB) 
[Units: Participants]
     
Hispanic or Latino   4   2   6 
Not Hispanic or Latino   10   12   22 
Unknown or Not Reported   0   0   0 
Race (NIH/OMB) 
[Units: Participants]
     
American Indian or Alaska Native   0   0   0 
Asian   0   1   1 
Native Hawaiian or Other Pacific Islander   0   0   0 
Black or African American   2   1   3 
White   12   11   23 
More than one race   0   0   0 
Unknown or Not Reported   0   1   1 
Region of Enrollment 
[Units: Participants]
     
United States   14   14   28 
Pre-ASCT Response [1] 
[Units: Participants]
     
Complete Response (CR)   5   3   8 
Very Good Partial Response (VGPR)   5   4   9 
Partial Response (PR)   4   7   11 
[1] At pre-ASCT evaluation, subjects must have met the International Neuroblastoma Response Criteria (INRC) for complete response (CR), very good partial response (VGPR) or partial response (PR) for primary site, soft tissue metastases, and bone metastases. Subjects who met those criteria were also required to meet the protocol specified criteria for bone marrow response.


  Outcome Measures
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1.  Primary:   Area Under the Plasma Concentration Curve (AUC)   [ Time Frame: PK samples obtained during Courses 1 and 3: Days 0, 3, 4, 5, 6, 7, 9, 10, 11, 14, 15, 16, 17; PK samples obtained during Courses 2 and 4: Days 0, 7, 10; End of Treatment ]

2.  Primary:   Peak Plasma Concentration (Cmax)   [ Time Frame: PK samples obtained during Courses 1 and 3: Days 0, 3, 4, 5, 6, 7, 9, 10, 11, 14, 15, 16, 17; PK samples obtained during Courses 2 and 4: Days 0, 7, 10; End of Treatment ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Allison Lim
Organization: United Therapeutics Corporation
phone: 919-425-8799
e-mail: alim@unither.com



Responsible Party: United Therapeutics
ClinicalTrials.gov Identifier: NCT01592045     History of Changes
Other Study ID Numbers: DIV-NB-201
Study First Received: April 30, 2012
Results First Received: June 3, 2015
Last Updated: August 20, 2015
Health Authority: United States: Food and Drug Administration