ABT-751 in Treating Children With Neuroblastoma That Has Relapsed or Not Responded to Previous Treatment

• Sponsor: Children's Oncology Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT00436852
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 92
• Locations: 12
• Arms: 2
• Duration (Months): 98.9
• Patients Per Site: 7.7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This phase II trial is studying how well ABT-751 works in treating children with neuroblastoma that has relapsed or not responded to previous treatment. Drugs used in chemotherapy, such as ABT-751, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

Condition or Disease	Intervention/Treatment	Phase
Disseminated Neuroblastoma; Recurrent Neuroblastoma	Drug: ABT-751; Procedure: quality-of-life assessment	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. Compare the time to disease progression in children with refractory or relapsed neuroblastoma treated with ABT-751 vs historical controls.

SECONDARY OBJECTIVES:

1. Determine the objective response rate in patients with measurable disease treatment with this drug.

2. Determine whether ABT-751 improves quality of life of these patients. III. Determine the toxicity of ABT-751. IV. Determine the pharmacokinetic profile of ABT-751 in these patients.

OUTLINE:

Patients receive oral ABT-751 once daily on days 1-7. Treatment repeats every 21 days for 52 courses in the absence of disease progression or unacceptable toxicity.

Blood is collected periodically during course 1 for pharmacokinetic studies. Quality of life is assessed at baseline and prior to each course of treatment.

After completion of study treatment, patients are followed up for up to 5.1 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 92 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of ABT-751, an Orally Bioavailable Tubulin Binding Agent, in Children With Relapsed or Refractory Neuroblastoma
• Study Start Date: Jan 1, 2007
• Actual Primary Completion Date: Sep 1, 2010
• Actual Study Completion Date: Mar 30, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Measurable disease by CT or MRI scan (ABT-751 chemotherapy) Patients receive oral ABT-751 (200 mg/m2) once daily on days 1-7. Treatment repeats every 21 days for 52 courses in the absence of disease progression or unacceptable toxicity. Quality-of-life assessment at baseline and prior to each course of treatment. A pharmacological study (pharmacokinetic profile of ABT-751) will be determined.	Drug: ABT-751; Given orally; Other Names: E7010 ; Procedure: quality-of-life assessment; Ancillary studies; Other Names: quality of life assessment
Experimental: Evaluable by I-MIBG scintigraphy (ABT-751) Patients receive oral ABT-751 (200 mg/m2) once daily on days 1-7. Treatment repeats every 21 days for 52 courses in the absence of disease progression or unacceptable toxicity. Quality-of-life assessment at baseline and prior to each course of treatment. A pharmacological study (pharmacokinetic profile of ABT-751) will be determined.	Drug: ABT-751; Given orally; Other Names: E7010 ; Procedure: quality-of-life assessment; Ancillary studies; Other Names: quality of life assessment

Outcome Measures

Primary Outcome Measures

1. Median Time to Progression as Assessed by Response Evaluation Criteria in Solid Tumors [From time to enrollment to death due to any cause, assessed up to 5.1 years]

   Median time to progression observed on ABT-751, along with 95% confidence intervals.

2. 1-year Progression-free Survival [From the day of enrollment to the date of disease progression/recurrence , or the date of death (all causes of mortality) if disease progression/recurrence is not reached, assessed up to 1 yr. Pts were to be followed for 5 yrs after completion of therapy]

   PFS probabilities calculated using the Kaplan-Meier method, along 95% confidence intervals, separately for each stratum.

Secondary Outcome Measures

1. Objective Response Rate [Duration of protocol therapy, up to 3 years]

   The percentage of patients who are responders will be tabulated, including a 95% confidence interval on the percentage. Responders were defined as patients who achieved a best overall response of complete response (CR) or partial response (PR) at any time on the study including patients who achieved ≥PR and later had progressive disease or relapse. Response in patients with measurable disease will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 or by Curie criteria for measuring response by MIBG scans in patients with evaluable disease by 123I-MIBG scan. Per RECIST: CR= Disappearance of all target lesions; PR= at least 30% decrease in the sum of the longest diameter of target lesions. Per Curie criteria: CR= complete resolution of all MIBG positive lesions; PR= resolution of at least one MIBG positive lesion with persistence of other MIBG positive lesions.

2. Quality of Life Measured by PedsQL™ Generic Core Scale Version 4.0 [At baseline]

   The QOL score will be reverse linearly transformed to a 0-100 percentage point scale (0=100, 1=75, 2=50, 3=25, 4=0), with higher scores indicating better health-related quality of life, and the average of all 23 items will be calculated as the composite score.

3. Percentage of Participants With Grade 3 or Higher Toxicity [From enrollment until 30 days after the end of protocol therapy]

   Percentage of patients with at least one Grade 3 or higher toxicity, as assessed by Common Terminology Criteria for Adverse Events version 3.0, will be tabulated.

4. Pharmacokinetics of ABT-751: Cmax [After the first dose of ABT-751, at 0.5, 1, 2, 3, 5, 8, 10-12, and 24 hours post-dose.]

   Values of the maximum observed concentration (Cmax) will be determined for the first dose.Descriptive statistics for these variables will be provided.

5. Pharmacokinetics of ABT-751: Tmax [After the first dose of ABT-751, at 0.5, 1, 2, 3, 5, 8, 10-12, and 24 hours post-dose.]

   Values of the time to maximum observed concentration (Tmax) will be determined for the first dose.Descriptive statistics for these variables will be provided.

6. Pharmacokinetics of ABT-751: AUC [After the first dose of ABT-751, at 0.5, 1, 2, 3, 5, 8, 10-12, and 24 hours post-dose.]

   Values of the area under concentration time curve [AUC(0-∞)] will be determined for the first dose. Descriptive statistics for these variables will be provided.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A to 21 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Histologically or cytologically confirmed neuroblastoma meeting the following criteria:

• Refractory or relapsed disease

• No curative treatment option and no additional therapy proven to prolong survival with an acceptable quality of life is available

• Evidence of disease progression (enlargement of existing measurable tumors or the appearance of new tumors) during prior treatment OR biopsy-proven viable neuroblastoma if stable disease but refractory to prior treatment

• Previously irradiated soft tissue or bony lesion must meet ≥ 1 of the following criteria:

• Viable neuroblastoma determined by biopsy ≥ 6 weeks after radiation therapy

• Growth in the lesion determined by CT scan or MRI

• Measurable or evaluable disease

• Measurable disease is defined as ≥ 20 mm in ≥ 1 dimension by MRI, CT scan, or x-ray OR ≥ 10 mm in ≥ 1 dimension by spiral CT scan

• Evaluable disease is defined as iodine I 123 metaiodobenzylguanidine (^123I MIBG)-positive lesion at ≥ 1 site

• Must not have measurable disease by CT scan or MRI

• No elevated urinary catecholamines and/or bone marrow evidence of tumor, without measurable or evaluable disease by imaging modalities (CT scan, MRI, or ^123I MIBG)

• Karnofsky performance status (PS) 50-100% (> 16 years of age) OR Lansky PS 50-100% (≤ 16 years of age)

• Life expectancy ≥ 8 weeks

• Hemoglobin ≥ 7.5 g/dL (transfusions allowed)

• Absolute neutrophil count > 250/mm³

• Platelet count > 25,000/mm³ (without platelet transfusion support for ≥ 7 days)

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)

• ALT < 5 times ULN

• Creatinine normal for age and gender as follows: OR creatinine clearance or radioisotope glomerular filtration rate ≥ 60 mL/min

• No greater than 0.4 mg/dL (≤ 5 months)

• No greater than 0.5 mg/dL (6 months-11 months)

• No greater than 0.6 mg/dL (1 year-23 months)

• No greater than 0.8 mg/dL (2 years-5 years)

• No greater than 1.0 mg/dL (6 years-9 years)

• No greater than 1.2 mg/dL (10 years-12 years)

• No greater than 1.4 mg/dL (13 years and over [female])

• No greater than 1.5 mg/dL (13 years to 15 years [male])

• No greater than 1.7 mg/dL (16 years and over [male])

• Shortening fraction ≥ 27% by echocardiogram

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective double-barrier contraception during and for 90 days after completion of study treatment

• Seizure disorder allowed if controlled and receiving anticonvulsants

• Neurologic toxicity from prior therapy or tumor involvement ≤ grade 2

• No evidence of active graft-vs-host disease

• No allergy to sulfa-containing medications

• No known HIV positivity

• No clinically significant unrelated systemic illness (e.g., serious infection) that would limit study compliance

• Concurrent filgrastim (G-CSF) allowed if medically indicated

• Recovered from all prior therapy

• No prior ABT-751

• More than 2 weeks since prior myelosuppressive chemotherapy

• More than 7 days since prior anticancer biologic agents (e.g., retinoids)

• More than 4 weeks since prior palliative radiation therapy (small port) or therapeutic ^123I MIBG

• More than 6 weeks since prior substantial radiation therapy (> 50% pelvis, craniospinal, or total-body radiation)

• More than 4 months since prior allogeneic stem cell transplantation (SCT) (2 months for autologous SCT) and recovered

• Infusion of autologous peripheral blood mononuclear cells without high-dose chemotherapy or preparative regimen is not considered SCT

• More than 30 days since prior investigational drug therapy

• More than 30 days since prior immunotherapy (monoclonal antibody therapy or vaccine therapy)

• More than 1 week since prior growth factor treatment

• No other concurrent anticancer agents, including chemotherapy, immunomodulating agents, or biologic therapy (retinoids)

• No concurrent radiation therapy, including palliative radiation therapy

• No concurrent treatment for graft-vs-host disease

• No concurrent epoetin alfa, sargramostim (GM-CSF), or interleukin-11

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	University of Chicago Comprehensive Cancer Center	Chicago	Illinois	United States	60637-1470
3	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115
4	C S Mott Children's Hospital	Ann Arbor	Michigan	United States	48109
5	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
6	Columbia University Medical Center	New York	New York	United States	10032
7	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229
8	Nationwide Children's Hospital	Columbus	Ohio	United States	43205
9	Oregon Health and Science University	Portland	Oregon	United States	97239
10	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
11	Cook Children's Medical Center	Fort Worth	Texas	United States	76104
12	Hospital for Sick Children	Toronto	Ontario	Canada	M5G 1X8

Sponsors and Collaborators

• Children's Oncology Group
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Elizabeth Fox, MD, Children's Oncology Group

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Children's Oncology Group
• ClinicalTrials.gov Identifier: NCT00436852
• Other Study ID Numbers: ANBL0621; NCI-2009-00402; NCI-07-C-0074; CDR0000529858; NCI-P6554; U10CA098543; COG-ANBL0621
• First Posted: Feb 19, 2007
• Last Update Posted: Jul 17, 2019
• Last Verified: Jul 1, 2019

• Additional relevant MeSH terms: Neuroblastoma

Study Results

Participant Flow

Arm/Group Title	Disease Evaluable by I-MIBG Scintigraphy (ABT-751)	Measurable Disease by CT or MRI Scan (ABT-751)
Arm/Group Description	Patients receive oral ABT-751 (200 mg/m2) once daily on days 1-7. Treatment repeats every 21 days for 52 courses in the absence of disease progression or unacceptable toxicity. Quality-of-life assessment at baseline and prior to each course of treatment. A pharmacological study (pharmacokinetic profile of ABT-751) will be determined.	Patients receive oral ABT-751 (200 mg/m2) once daily on days 1-7. Treatment repeats every 21 days for 52 courses in the absence of disease progression or unacceptable toxicity. Quality-of-life assessment at baseline and prior to each course of treatment. A pharmacological study (pharmacokinetic profile of ABT-751) will be determined.
Period Title: Overall Study
STARTED	45	47
COMPLETED	10	2
NOT COMPLETED	35	45

Baseline Characteristics

Arm/Group Title	Disease Evaluable by I-MIBG Scintigraphy (ABT-751)	Measurable Disease by CT or MRI Scan (ABT-751)	Total
Arm/Group Description	Patients receive oral ABT-751 (200 mg/m2) once daily on days 1-7. Treatment repeats every 21 days for 52 courses in the absence of disease progression or unacceptable toxicity. Quality-of-life assessment at baseline and prior to each course of treatment. A pharmacological study (pharmacokinetic profile of ABT-751) will be determined.	Patients receive oral ABT-751 (200 mg/m2) once daily on days 1-7. Treatment repeats every 21 days for 52 courses in the absence of disease progression or unacceptable toxicity. Quality-of-life assessment at baseline and prior to each course of treatment. A pharmacological study (pharmacokinetic profile of ABT-751) will be determined.	Total of all reporting groups
Overall Participants	45	47	92
Age (Count of Participants)
<=18 years	42 93.3%	45 95.7%	87 94.6%
Between 18 and 65 years	3 6.7%	2 4.3%	5 5.4%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [years]	8.46	7.55	8.00
Sex: Female, Male (Count of Participants)
Female	14 31.1%	21 44.7%	35 38%
Male	31 68.9%	26 55.3%	57 62%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	5 11.1%	4 8.5%	9 9.8%
Not Hispanic or Latino	35 77.8%	41 87.2%	76 82.6%
Unknown or Not Reported	5 11.1%	2 4.3%	7 7.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	2 4.3%	2 2.2%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	8 17.8%	9 19.1%	17 18.5%
White	30 66.7%	30 63.8%	60 65.2%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	7 15.6%	6 12.8%	13 14.1%
Region of Enrollment (participants) [Number]
United States	45 100%	36 76.6%	81 88%
Canada	0 0%	10 21.3%	10 10.9%
Jamaica	0 0%	1 2.1%	1 1.1%

Outcome Measures

1. Primary Outcome

Title	Median Time to Progression as Assessed by Response Evaluation Criteria in Solid Tumors
Description	Median time to progression observed on ABT-751, along with 95% confidence intervals.
Time Frame	From time to enrollment to death due to any cause, assessed up to 5.1 years

Outcome Measure Data

Analysis Population Description

The protocol-specified definition of evaluability was applied. This was not an intention-to-treat analysis because patients who did not receive study drug were excluded (inevaluable).

Arm/Group Title	Disease Evaluable by I-MIBG Scintigraphy (ABT-751)	Measurable Disease by CT or MRI Scan (ABT-751)
Arm/Group Description	Patients who met study eligibility criteria and receive at least one dose of oral ABT-751 were evaluable for the efficacy analysis.	Patients who met study eligibility criteria and receive at least one dose of oral ABT-751 were evaluable for the efficacy analysis.
Measure Participants	44	47
Median (95% Confidence Interval) [days]	45	42

2. Primary Outcome

Title	1-year Progression-free Survival
Description	PFS probabilities calculated using the Kaplan-Meier method, along 95% confidence intervals, separately for each stratum.
Time Frame	From the day of enrollment to the date of disease progression/recurrence , or the date of death (all causes of mortality) if disease progression/recurrence is not reached, assessed up to 1 yr. Pts were to be followed for 5 yrs after completion of therapy

Outcome Measure Data

Analysis Population Description

The protocol-specified definition of evaluability was applied. This was not an intention-to-treat analysis because patients who did not receive study drug were excluded (inevaluable).

Arm/Group Title	Disease Evaluable by I-MIBG Scintigraphy (ABT-751)	Measurable Disease by CT or MRI Scan (ABT-751)
Arm/Group Description	Patients who met study eligibility criteria and receive at least one dose of oral ABT-751 were evaluable for the efficacy analysis.	Patients who met study eligibility criteria and receive at least one dose of oral ABT-751 were evaluable for the efficacy analysis.
Measure Participants	44	47
Number (95% Confidence Interval) [percent probability]	19	7

3. Secondary Outcome

Title	Objective Response Rate
Description	The percentage of patients who are responders will be tabulated, including a 95% confidence interval on the percentage. Responders were defined as patients who achieved a best overall response of complete response (CR) or partial response (PR) at any time on the study including patients who achieved ≥PR and later had progressive disease or relapse. Response in patients with measurable disease will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.0 or by Curie criteria for measuring response by MIBG scans in patients with evaluable disease by 123I-MIBG scan. Per RECIST: CR= Disappearance of all target lesions; PR= at least 30% decrease in the sum of the longest diameter of target lesions. Per Curie criteria: CR= complete resolution of all MIBG positive lesions; PR= resolution of at least one MIBG positive lesion with persistence of other MIBG positive lesions.
Time Frame	Duration of protocol therapy, up to 3 years

Outcome Measure Data

Analysis Population Description

Patients who met study eligibility criteria and received at least one dose of oral ABT-751 were evaluable for the response analysis.

Arm/Group Title	Disease Evaluable by I-MIBG Scintigraphy (ABT-751)	Measurable Disease by CT or MRI Scan (ABT-751)
Arm/Group Description	Patients with evaluable disease by (123)I-MIBG scintigraphy (positive at a minimum of one site) with or without bone marrow metastases but without RECIST (Response Evaluation in Solid Tumors) measureable disease.	Patients with RECIST measurable disease on CT or MRI scan, with or without (123)I-MIBG positive disease, with or without bone marrow metastases.
Measure Participants	43	47
Number (95% Confidence Interval) [Percentage of patients]	12	2

4. Secondary Outcome

Title	Quality of Life Measured by PedsQL™ Generic Core Scale Version 4.0
Description	The QOL score will be reverse linearly transformed to a 0-100 percentage point scale (0=100, 1=75, 2=50, 3=25, 4=0), with higher scores indicating better health-related quality of life, and the average of all 23 items will be calculated as the composite score.
Time Frame	At baseline

Outcome Measure Data

Analysis Population Description

Eligible patients with a QOL evaluation at baseline were included in the analysis.

Arm/Group Title	Disease Evaluable by I-MIBG Scintigraphy (ABT-751)	Measurable Disease by CT or MRI Scan (ABT-751)
Arm/Group Description	Patients with evaluable disease by (123)I-MIBG scintigraphy (positive at a minimum of one site) with or without bone marrow metastases but without RECIST (Response Evaluation in Solid Tumors) measureable disease.	Patients with RECIST measurable disease on CT or MRI scan, with or without (123)I-MIBG positive disease, with or without bone marrow metastases.
Measure Participants	37	34
Median (Full Range) [Scores on a scale]	80	68

5. Secondary Outcome

Title	Percentage of Participants With Grade 3 or Higher Toxicity
Description	Percentage of patients with at least one Grade 3 or higher toxicity, as assessed by Common Terminology Criteria for Adverse Events version 3.0, will be tabulated.
Time Frame	From enrollment until 30 days after the end of protocol therapy

Outcome Measure Data

Analysis Population Description

All eligible patients who received at least 1 dose of ABT-751 were evaluable for toxicity and included in the analysis.

Arm/Group Title	Disease Evaluable by I-MIBG Scintigraphy (ABT-751)	Measurable Disease by CT or MRI Scan (ABT-751)
Arm/Group Description	Patients with evaluable disease by (123)I-MIBG scintigraphy (positive at a minimum of one site) with or without bone marrow metastases but without RECIST (Response Evaluation in Solid Tumors) measureable disease.	Patients with RECIST measurable disease on CT or MRI scan, with or without (123)I-MIBG positive disease, with or without bone marrow metastases.
Measure Participants	44	47
Number [Percentage of patients]	75.0	72.3

6. Secondary Outcome

Title	Pharmacokinetics of ABT-751: Cmax
Description	Values of the maximum observed concentration (Cmax) will be determined for the first dose.Descriptive statistics for these variables will be provided.
Time Frame	After the first dose of ABT-751, at 0.5, 1, 2, 3, 5, 8, 10-12, and 24 hours post-dose.

Outcome Measure Data

Analysis Population Description

All eligible patients from Group 1 (Disease Evaluable by I-MIBG Scintigraphy (ABT-751)) and Group 2 (Measurable Disease by CT or MRI Scan (ABT-751)) who received the first dose of ABT-751 and participated in the pharmacokinetic studies were included in the analysis and are presented as a single Group, as the interest was in both groups combined.

Arm/Group Title	All Eligible Patients
Arm/Group Description	All eligible patients who received the first dose of ABT-751 and participated in the pharmacokinetic studies
Measure Participants	16
Median (Full Range) [mg/ml]	15.3

7. Secondary Outcome

Title	Pharmacokinetics of ABT-751: Tmax
Description	Values of the time to maximum observed concentration (Tmax) will be determined for the first dose.Descriptive statistics for these variables will be provided.
Time Frame	After the first dose of ABT-751, at 0.5, 1, 2, 3, 5, 8, 10-12, and 24 hours post-dose.

Outcome Measure Data

Analysis Population Description

All eligible patients from Group 1 (Disease Evaluable by I-MIBG Scintigraphy (ABT-751)) and Group 2 (Measurable Disease by CT or MRI Scan (ABT-751)) who received the first dose of ABT-751 and participated in the pharmacokinetic studies were included in the analysis and are presented as a single Group, as the interest was in both groups combined.

Arm/Group Title	All Eligible Patients
Arm/Group Description	All eligible patients who received the first dose of ABT-751 and participated in the pharmacokinetic studies
Measure Participants	16
Median (Full Range) [hours]	1

8. Secondary Outcome

Title	Pharmacokinetics of ABT-751: AUC
Description	Values of the area under concentration time curve [AUC(0-∞)] will be determined for the first dose. Descriptive statistics for these variables will be provided.
Time Frame	After the first dose of ABT-751, at 0.5, 1, 2, 3, 5, 8, 10-12, and 24 hours post-dose.

Outcome Measure Data

Analysis Population Description

All eligible patients from Group 1 (Disease Evaluable by I-MIBG Scintigraphy (ABT-751)) and Group 2 (Measurable Disease by CT or MRI Scan (ABT-751)) who received the first dose of ABT-751 and participated in the pharmacokinetic studies were included in the analysis and are presented as a single Group, as the interest was in both groups combined.

Arm/Group Title	All Eligible Patients
Arm/Group Description	All eligible patients who received the first dose of ABT-751 and participated in the pharmacokinetic studies
Measure Participants	16
Median (Full Range) [mg·hours/ml]	77.5

Adverse Events

Arm/Group Title	Disease Evaluable by I-MIBG Scintigraphy (ABT-751)		Measurable Disease by CT or MRI Scan (ABT-751)
Arm/Group Description	Patients who met study eligibility criteria and receive at least one dose of oral ABT-751 were evaluable for the efficacy analysis.		Patients who met study eligibility criteria and receive at least one dose of oral ABT-751 were evaluable for the efficacy analysis.
All Cause Mortality
	Disease Evaluable by I-MIBG Scintigraphy (ABT-751)		Measurable Disease by CT or MRI Scan (ABT-751)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Disease Evaluable by I-MIBG Scintigraphy (ABT-751)		Measurable Disease by CT or MRI Scan (ABT-751)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/44 (6.8%)		4/47 (8.5%)
Blood and lymphatic system disorders
Febrile neutropenia (fever, unk. origin,w/o infection,ANC<1x10e9, fever>=38.5C)	0/44 (0%)		2/47 (4.3%)
Hemoglobin	1/44 (2.3%)		2/47 (4.3%)
Cardiac disorders
Left ventricular diastolic dysfunction	0/44 (0%)		1/47 (2.1%)
Left ventricular systolic dysfunction	1/44 (2.3%)		1/47 (2.1%)
Gastrointestinal disorders
Constipation	2/44 (4.5%)		2/47 (4.3%)
Hemorrhage, GI - Rectum	1/44 (2.3%)		0/47 (0%)
Obstruction, GI - Small bowel NOS	0/44 (0%)		2/47 (4.3%)
Pain - Abdomen NOS	1/44 (2.3%)		0/47 (0%)
Vomiting	1/44 (2.3%)		2/47 (4.3%)
General disorders
Death not associated with CTCAE term - Death NOS	1/44 (2.3%)		0/47 (0%)
Death not associated with CTCAE term - Disease progression NOS	0/44 (0%)		1/47 (2.1%)
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)	1/44 (2.3%)		1/47 (2.1%)
Gait/walking: Extremity-lower (gait/walking)	0/44 (0%)		1/47 (2.1%)
Infections and infestations
Infection (clinical or microbiological Dx) w/ Gr 3-4 neutrophils, ANC<1.0x10e9 - Blood	0/44 (0%)		1/47 (2.1%)
Infection (clinical or microbiological Dx) w/ Gr 3-4 neutrophils, ANC<1.0x10e9 - Paranasal	1/44 (2.3%)		0/47 (0%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Blood	2/44 (4.5%)		0/47 (0%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Bone (osteomyelitis)	0/44 (0%)		1/47 (2.1%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Catheter-related	1/44 (2.3%)		1/47 (2.1%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Sinus	0/44 (0%)		1/47 (2.1%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Skin (cellulitis)	2/44 (4.5%)		0/47 (0%)
Infection with normal ANC or Grade 1 or 2 neutrophils - Upper airway NOS	2/44 (4.5%)		0/47 (0%)
Infection with unknown ANC - Blood	0/44 (0%)		1/47 (2.1%)
Infection with unknown ANC - Middle ear (otitis media)	1/44 (2.3%)		0/47 (0%)
Investigations
Neutrophils/granulocytes (ANC/AGC)	1/44 (2.3%)		0/47 (0%)
Platelets	1/44 (2.3%)		0/47 (0%)
Weight loss	1/44 (2.3%)		0/47 (0%)
Metabolism and nutrition disorders
Anorexia	1/44 (2.3%)		1/47 (2.1%)
Dehydration	1/44 (2.3%)		0/47 (0%)
Hypoglycemia: Glucose, serum-low (hypoglycemia)	0/44 (0%)		1/47 (2.1%)
Hypokalemia: Potassium, serum-low (hypokalemia)	0/44 (0%)		2/47 (4.3%)
Hyponatremia: Sodium, serum-low (hyponatremia)	0/44 (0%)		1/47 (2.1%)
Musculoskeletal and connective tissue disorders
Muscle weakness, generalized or specific area (not due to neuropathy) - Whole body/generalized	1/44 (2.3%)		0/47 (0%)
Pain - Bone	1/44 (2.3%)		0/47 (0%)
Pain - Extremity-limb	3/44 (6.8%)		3/47 (6.4%)
Pain - Muscle	0/44 (0%)		1/47 (2.1%)
Nervous system disorders
Neuropathy: sensory	1/44 (2.3%)		4/47 (8.5%)
Pain - Head/headache	0/44 (0%)		1/47 (2.1%)
Pain - Neuralgia/peripheral nerve	0/44 (0%)		3/47 (6.4%)
Syncope (fainting)	1/44 (2.3%)		0/47 (0%)
Taste alteration (dysgeusia)	0/44 (0%)		1/47 (2.1%)
Psychiatric disorders
Insomnia	0/44 (0%)		1/47 (2.1%)
Mood alteration - Agitation	1/44 (2.3%)		0/47 (0%)
Mood alteration - Anxiety	0/44 (0%)		1/47 (2.1%)
Mood alteration - Depression	0/44 (0%)		1/47 (2.1%)
Personality/behavioral	1/44 (2.3%)		0/47 (0%)
Respiratory, thoracic and mediastinal disorders
" Bronchospasm, wheezing"	1/44 (2.3%)		0/47 (0%)
Dyspnea (shortness of breath)	0/44 (0%)		1/47 (2.1%)
Hypoxia	0/44 (0%)		1/47 (2.1%)
Vascular disorders
Hypertension	0/44 (0%)		1/47 (2.1%)
Hypotension	1/44 (2.3%)		0/47 (0%)
Other (Not Including Serious) Adverse Events
	Disease Evaluable by I-MIBG Scintigraphy (ABT-751)		Measurable Disease by CT or MRI Scan (ABT-751)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/44 (38.6%)		24/47 (51.1%)
Blood and lymphatic system disorders
Hemoglobin	12/44 (27.3%)	12	24/47 (51.1%)	24
Gastrointestinal disorders
Constipation	8/44 (18.2%)	8	12/47 (25.5%)	12
Diarrhea	5/44 (11.4%)	5	8/47 (17%)	8
Nausea	13/44 (29.5%)	13	16/47 (34%)	16
Pain - Abdomen NOS	9/44 (20.5%)	9	11/47 (23.4%)	11
Pain - Stomach	3/44 (6.8%)	3	0/47 (0%)	0
Vomiting	6/44 (13.6%)	6	11/47 (23.4%)	11
General disorders
" Fatigue (asthenia, lethargy, malaise)"	13/44 (29.5%)	13	9/47 (19.1%)	9
" Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)"	6/44 (13.6%)	6	12/47 (25.5%)	12
Infections and infestations
Infection with normal ANC or Grade 1 or 2 neutrophils - Sinus	4/44 (9.1%)	4	0/47 (0%)	0
Investigations
"ALT, SGPT (serum glutamic pyruvic transaminase)"	9/44 (20.5%)	9	14/47 (29.8%)	14
"AST: AST, SGOT(serum glutamic oxaloacetic transaminase)"	7/44 (15.9%)	7	14/47 (29.8%)	14
" Cholesterol: Cholesterol, serum-high (hypercholestremia)"	0/44 (0%)	0	3/47 (6.4%)	3
Creatinine	0/44 (0%)	0	4/47 (8.5%)	4
GGT: GGT (gamma-Glutamyl transpeptidase)	4/44 (9.1%)	4	4/47 (8.5%)	4
Leukocytes (total WBC)	17/44 (38.6%)	17	19/47 (40.4%)	19
Lymphopenia	5/44 (11.4%)	5	10/47 (21.3%)	10
Neutrophils/granulocytes (ANC/AGC)	17/44 (38.6%)	17	14/47 (29.8%)	14
Platelets	13/44 (29.5%)	13	18/47 (38.3%)	18
Weight loss	4/44 (9.1%)	4	4/47 (8.5%)	4
Metabolism and nutrition disorders
Anorexia	7/44 (15.9%)	7	9/47 (19.1%)	9
"Albumin, serum-low (hypoalbuminemia)"	0/44 (0%)	0	12/47 (25.5%)	12
"Bicarbonate, serum-low"	0/44 (0%)	0	4/47 (8.5%)	4
Dehydration	4/44 (9.1%)	4	0/47 (0%)	0
"Hypercalcemia: Calcium, serum-high (hypercalcemia)"	0/44 (0%)	0	4/47 (8.5%)	4
"Hyperglycemia: Glucose, serum-high (hyperglycemia)"	7/44 (15.9%)	7	12/47 (25.5%)	12
"Hypermagnesemia: Magnesium, serum-high (hypermagnesemia)"	0/44 (0%)	0	5/47 (10.6%)	5
"Hypertriglyceridemia: Triglyceride, serum-high (hypertriglyceridemia)"	0/44 (0%)	0	6/47 (12.8%)	6
"Hypocalcemia: Calcium, serum-low (hypocalcemia)"	0/44 (0%)	0	6/47 (12.8%)	6
"Hypoglycemia: Glucose, serum-low (hypoglycemia)"	0/44 (0%)	0	3/47 (6.4%)	3
"Hypokalemia: Potassium, serum-low (hypokalemia)"	4/44 (9.1%)	4	11/47 (23.4%)	11
"Hypomagnesemia: Magnesium, serum-low (hypomagnesemia)"	3/44 (6.8%)	3	5/47 (10.6%)	5
"Hyponatremia: Sodium, serum-low (hyponatremia)"	6/44 (13.6%)	6	14/47 (29.8%)	14
"Hypophosphatemia: Phosphate, serum-low (hypophosphatemia)"	0/44 (0%)	0	8/47 (17%)	8
Musculoskeletal and connective tissue disorders
Pain - Back	3/44 (6.8%)	3	0/47 (0%)	0
Pain - Bone	0/44 (0%)	0	3/47 (6.4%)	3
Pain - Extremity-limb	11/44 (25%)	11	11/47 (23.4%)	11
Pain - Joint	4/44 (9.1%)	4	3/47 (6.4%)	3
Pain - Muscle	0/44 (0%)	0	3/47 (6.4%)	3
Nervous system disorders
Neuropathy: sensory	12/44 (27.3%)	12	10/47 (21.3%)	10
Pain - Head/headache	7/44 (15.9%)	7	9/47 (19.1%)	9
Psychiatric disorders
Insomnia	6/44 (13.6%)	6	3/47 (6.4%)	3
Mood alteration - Agitation	0/44 (0%)	0	3/47 (6.4%)	3
Mood alteration - Anxiety	3/44 (6.8%)	3	0/47 (0%)	0
Mood alteration - Depression	3/44 (6.8%)	3	0/47 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	4/44 (9.1%)	4	4/47 (8.5%)	4
" Hemorrhage, pulmonary/upper respiratory - Nose"	0/44 (0%)	0	3/47 (6.4%)	3
Pain - Throat/pharynx/larynx	3/44 (6.8%)	3	3/47 (6.4%)	3
Skin and subcutaneous tissue disorders
Rash/desquamation	0/44 (0%)	0	3/47 (6.4%)	3
Vascular disorders
Hypertension	0/44 (0%)	0	3/47 (6.4%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT 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.