Trial Outcomes & Findings for Irinotecan and Temozolomide in Treating Young Patients With Recurrent Neuroblastoma (NCT NCT00311584)

Last Updated: 2014-09-30

Results Overview

The patient's best overall response obtained during Reporting Periods 1 and 2 will be scored as "best response". Patients enrolled on Stratum 1 with bone marrow disease, a responder has no tumor cells detectable by routine morphology on 2 subsequent bilateral bone marrow aspirates and biopsies done at least 3 weeks apart. For patients enrolled on stratum 1 with MIBG only disease, response will be assessed using the Curie scale. Patients who have complete resolution of all MIBG positive lesions (CR) or resolution of at least one MIBG positive lesion with persistence of other lesions (PR) will be considered responders. For Stratum 2 a responder is defined to be a patient who achieves a best overall response of CR, VGPR or PR from CT/MRI scans from central review using (RECIST) Response Evaluation Criteria in Solid Tumor. A responder is defined to be a patient who achieves a best overall response of CR (Complete Response), VGPR (Very Good Partial Response) or PR (Partial Response).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

59 participants

Primary outcome timeframe

up to 6 courses of therapy, or about 6 months

Results posted on

2014-09-30

Participant Flow

Participant milestones

Participant milestones
Measure	Disease Eval by Bone Marrow or MIBG (Irinotecan/Temozolomide) Evaluation by bone marrow or MIBG scan (metaiodobenzylguanidine scan, a radiopharmaceutical). Patients receive irinotecan hydrochloride IV (10 mg/m2/dose) over 1 hour on days 1-5 and 8-12 and oral temozolomide (100 mg/m2/dose) on days 1-5. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. irinotecan hydrochloride : Given IV temozolomide : Given IV	Disease Measurable by CT or MRI Scan (Irinotecan/Temozolomide) Measurable by CT scan (Computed Tomography) or MRI scan (Magnetic Resonance Imaging). Patients receive irinotecan hydrochloride (10 mg/m2/dose) over 1 hour on days 1-5 and 8-12 and oral temozolomide (100 mg/m2/dose) on days 1-5. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. irinotecan hydrochloride : Given IV temozolomide : Given IV
Overall Study STARTED	29	30
Overall Study COMPLETED	9	7
Overall Study NOT COMPLETED	20	23

Reasons for withdrawal

Reasons for withdrawal
Measure	Disease Eval by Bone Marrow or MIBG (Irinotecan/Temozolomide) Evaluation by bone marrow or MIBG scan (metaiodobenzylguanidine scan, a radiopharmaceutical). Patients receive irinotecan hydrochloride IV (10 mg/m2/dose) over 1 hour on days 1-5 and 8-12 and oral temozolomide (100 mg/m2/dose) on days 1-5. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. irinotecan hydrochloride : Given IV temozolomide : Given IV	Disease Measurable by CT or MRI Scan (Irinotecan/Temozolomide) Measurable by CT scan (Computed Tomography) or MRI scan (Magnetic Resonance Imaging). Patients receive irinotecan hydrochloride (10 mg/m2/dose) over 1 hour on days 1-5 and 8-12 and oral temozolomide (100 mg/m2/dose) on days 1-5. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. irinotecan hydrochloride : Given IV temozolomide : Given IV
Overall Study Death	1	0
Overall Study Lack of Efficacy	12	15
Overall Study Physician Decision	4	5
Overall Study Withdrawal by Subject	1	1
Overall Study ineligible	2	2

Baseline Characteristics

Irinotecan and Temozolomide in Treating Young Patients With Recurrent Neuroblastoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Disease Eval by Bone Marrow or MIBG (Irinotecan/Temozolomide) n=29 Participants Evaluation by bone marrow or MIBG scan (metaiodobenzylguanidine scan, a radiopharmaceutical). Patients receive irinotecan hydrochloride (10 mg/m2/dose) over 1 hour on days 1-5 and 8-12 and oral temozolomide (100 mg/m2/dose) on days 1-5. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. irinotecan hydrochloride : Given IV temozolomide : Given IV	Disease Measurable by CT or MRI Scan (Irinotecan/Temozolomide) n=30 Participants Measurable by CT scan (Computed Tomography) or MRI scan (Magnetic Resonance Imaging). Patients receive irinotecan hydrochloride (10 mg/m2/dose) over 1 hour on days 1-5 and 8-12 and oral temozolomide (100 mg/m2/dose) on days 1-5. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. irinotecan hydrochloride : Given IV temozolomide : Given IV	Total n=59 Participants Total of all reporting groups
Age, Categorical <=18 years	28 Participants n=5 Participants	30 Participants n=7 Participants	58 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	1922 days n=5 Participants	1562 days n=7 Participants	1742 days n=5 Participants
Sex: Female, Male Female	15 Participants n=5 Participants	11 Participants n=7 Participants	26 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants	19 Participants n=7 Participants	33 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	26 Participants n=5 Participants	22 Participants n=7 Participants	48 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) White	20 Participants n=5 Participants	21 Participants n=7 Participants	41 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Region of Enrollment United States	26 participants n=5 Participants	28 participants n=7 Participants	54 participants n=5 Participants
Region of Enrollment Canada	2 participants n=5 Participants	2 participants n=7 Participants	4 participants n=5 Participants
Region of Enrollment Australia	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants

PRIMARY outcome

Timeframe: up to 6 courses of therapy, or about 6 months

Population: Patients were evaluable for inclusion in the analysis of response if eligible, had an event (relapse, PD, death or secondary malignancy) any time after enrollment, or completed at least 2 courses of Irinotecan/Temozolomide therapy. Patients off therapy before completion of 2 courses by choice or toxicity were not evaluable for response analysis.

Outcome measures

Outcome measures
Measure	Disease Eval by Bone Marrow or MIBG (Irinotecan/Temozolomide) n=27 Participants Evaluation by bone marrow or MIBG scan (metaiodobenzylguanidine scan, a radiopharmaceutical). Patients receive irinotecan hydrochloride (10 mg/m2/dose) over 1 hour on days 1-5 and 8-12 and oral temozolomide (100 mg/m2/dose) on days 1-5. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. irinotecan hydrochloride : Given IV temozolomide : Given IV	Disease Measurable by CT or MRI Scan (Irinotecan/Temozolomide) n=28 Participants Measurable by CT scan (Computed Tomography) or MRI scan (Magnetic Resonance Imaging). Patients receive irinotecan hydrochloride (10 mg/m2/dose) over 1 hour on days 1-5 and 8-12 and oral temozolomide (100 mg/m2/dose) on days 1-5. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. irinotecan hydrochloride : Given IV temozolomide : Given IV
Overall Response - Complete Response (CR), Very Good Partial Response (VGPR) and Partial Response (PR)	5 participants	3 participants

Adverse Events

Disease Eval by Bone Marrow or MIBG (Irinotecan/Temozolomide)

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Disease Measurable by CT or MRI Scan (Irinotecan/Temozolomide)

Serious events: 1 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Disease Eval by Bone Marrow or MIBG (Irinotecan/Temozolomide) n=27 participants at risk Evaluation by bone marrow or MIBG scan (metaiodobenzylguanidine scan, a radiopharmaceutical). Patients receive irinotecan hydrochloride (10 mg/m2/dose) over 1 hour on days 1-5 and 8-12 and oral temozolomide (100 mg/m2/dose) on days 1-5. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. irinotecan hydrochloride : Given IV temozolomide : Given IV	Disease Measurable by CT or MRI Scan (Irinotecan/Temozolomide) n=28 participants at risk Measurable by CT scan (Computed Tomography) or MRI scan (Magnetic Resonance Imaging). Patients receive irinotecan hydrochloride (10 mg/m2/dose) over 1 hour on days 1-5 and 8-12 and oral temozolomide (100 mg/m2/dose) on days 1-5. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. irinotecan hydrochloride : Given IV temozolomide : Given IV
General disorders Death not associated with CTCAE term - Disease progression NOS	0.00% 0/27 • Duration of protocol therapy, which could be up to about 1 year Only eligible patients that received at least one dose of protocol therapy are included for Adverse event reporting (there were 2 ineligible patients on Stratum 1 (27 at risk) and 2 ineligible patients on Stratum 2 (28 at risk).	3.6% 1/28 • Duration of protocol therapy, which could be up to about 1 year Only eligible patients that received at least one dose of protocol therapy are included for Adverse event reporting (there were 2 ineligible patients on Stratum 1 (27 at risk) and 2 ineligible patients on Stratum 2 (28 at risk).

Other adverse events

Additional Information

Results Reporting Coordinator

Children's Oncology Group

Phone: 626-447-0064

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Must obtain prior Sponsor approval.
Publication restrictions are in place

Restriction type: OTHER

Measure	Disease Eval by Bone Marrow or MIBG (Irinotecan/Temozolomide) n=27 participants at risk Evaluation by bone marrow or MIBG scan (metaiodobenzylguanidine scan, a radiopharmaceutical). Patients receive irinotecan hydrochloride (10 mg/m2/dose) over 1 hour on days 1-5 and 8-12 and oral temozolomide (100 mg/m2/dose) on days 1-5. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. irinotecan hydrochloride : Given IV temozolomide : Given IV	Disease Measurable by CT or MRI Scan (Irinotecan/Temozolomide) n=28 participants at risk Measurable by CT scan (Computed Tomography) or MRI scan (Magnetic Resonance Imaging). Patients receive irinotecan hydrochloride (10 mg/m2/dose) over 1 hour on days 1-5 and 8-12 and oral temozolomide (100 mg/m2/dose) on days 1-5. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. irinotecan hydrochloride : Given IV temozolomide : Given IV
Investigations ALT, SGPT (serum glutamic pyruvic transaminase)	11.1% 3/27 • Duration of protocol therapy, which could be up to about 1 year Only eligible patients that received at least one dose of protocol therapy are included for Adverse event reporting (there were 2 ineligible patients on Stratum 1 (27 at risk) and 2 ineligible patients on Stratum 2 (28 at risk).	10.7% 3/28 • Duration of protocol therapy, which could be up to about 1 year Only eligible patients that received at least one dose of protocol therapy are included for Adverse event reporting (there were 2 ineligible patients on Stratum 1 (27 at risk) and 2 ineligible patients on Stratum 2 (28 at risk).
Investigations AST: AST, SGOT(serum glutamic oxaloacetic transaminase)	14.8% 4/27 • Duration of protocol therapy, which could be up to about 1 year Only eligible patients that received at least one dose of protocol therapy are included for Adverse event reporting (there were 2 ineligible patients on Stratum 1 (27 at risk) and 2 ineligible patients on Stratum 2 (28 at risk).	7.1% 2/28 • Duration of protocol therapy, which could be up to about 1 year Only eligible patients that received at least one dose of protocol therapy are included for Adverse event reporting (there were 2 ineligible patients on Stratum 1 (27 at risk) and 2 ineligible patients on Stratum 2 (28 at risk).
Investigations Alkaline phosphatase	0.00% 0/27 • Duration of protocol therapy, which could be up to about 1 year Only eligible patients that received at least one dose of protocol therapy are included for Adverse event reporting (there were 2 ineligible patients on Stratum 1 (27 at risk) and 2 ineligible patients on Stratum 2 (28 at risk).	7.1% 2/28 • Duration of protocol therapy, which could be up to about 1 year Only eligible patients that received at least one dose of protocol therapy are included for Adverse event reporting (there were 2 ineligible patients on Stratum 1 (27 at risk) and 2 ineligible patients on Stratum 2 (28 at risk).
Gastrointestinal disorders Constipation	0.00% 0/27 • Duration of protocol therapy, which could be up to about 1 year Only eligible patients that received at least one dose of protocol therapy are included for Adverse event reporting (there were 2 ineligible patients on Stratum 1 (27 at risk) and 2 ineligible patients on Stratum 2 (28 at risk).	7.1% 2/28 • Duration of protocol therapy, which could be up to about 1 year Only eligible patients that received at least one dose of protocol therapy are included for Adverse event reporting (there were 2 ineligible patients on Stratum 1 (27 at risk) and 2 ineligible patients on Stratum 2 (28 at risk).
General disorders Fatigue (asthenia, lethargy, malaise)	7.4% 2/27 • Duration of protocol therapy, which could be up to about 1 year Only eligible patients that received at least one dose of protocol therapy are included for Adverse event reporting (there were 2 ineligible patients on Stratum 1 (27 at risk) and 2 ineligible patients on Stratum 2 (28 at risk).	0.00% 0/28 • Duration of protocol therapy, which could be up to about 1 year Only eligible patients that received at least one dose of protocol therapy are included for Adverse event reporting (there were 2 ineligible patients on Stratum 1 (27 at risk) and 2 ineligible patients on Stratum 2 (28 at risk).
General disorders Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0 x 10e9/L)	11.1% 3/27 • Duration of protocol therapy, which could be up to about 1 year Only eligible patients that received at least one dose of protocol therapy are included for Adverse event reporting (there were 2 ineligible patients on Stratum 1 (27 at risk) and 2 ineligible patients on Stratum 2 (28 at risk).	10.7% 3/28 • Duration of protocol therapy, which could be up to about 1 year Only eligible patients that received at least one dose of protocol therapy are included for Adverse event reporting (there were 2 ineligible patients on Stratum 1 (27 at risk) and 2 ineligible patients on Stratum 2 (28 at risk).
Blood and lymphatic system disorders Hemoglobin	25.9% 7/27 • Duration of protocol therapy, which could be up to about 1 year Only eligible patients that received at least one dose of protocol therapy are included for Adverse event reporting (there were 2 ineligible patients on Stratum 1 (27 at risk) and 2 ineligible patients on Stratum 2 (28 at risk).	25.0% 7/28 • Duration of protocol therapy, which could be up to about 1 year Only eligible patients that received at least one dose of protocol therapy are included for Adverse event reporting (there were 2 ineligible patients on Stratum 1 (27 at risk) and 2 ineligible patients on Stratum 2 (28 at risk).
Metabolism and nutrition disorders Hyperglycemia: Glucose, serum-high (hyperglycemia)	22.2% 6/27 • Duration of protocol therapy, which could be up to about 1 year Only eligible patients that received at least one dose of protocol therapy are included for Adverse event reporting (there were 2 ineligible patients on Stratum 1 (27 at risk) and 2 ineligible patients on Stratum 2 (28 at risk).	7.1% 2/28 • Duration of protocol therapy, which could be up to about 1 year Only eligible patients that received at least one dose of protocol therapy are included for Adverse event reporting (there were 2 ineligible patients on Stratum 1 (27 at risk) and 2 ineligible patients on Stratum 2 (28 at risk).
Metabolism and nutrition disorders Hypokalemia: Potassium, serum-low (hypokalemia)	14.8% 4/27 • Duration of protocol therapy, which could be up to about 1 year Only eligible patients that received at least one dose of protocol therapy are included for Adverse event reporting (there were 2 ineligible patients on Stratum 1 (27 at risk) and 2 ineligible patients on Stratum 2 (28 at risk).	7.1% 2/28 • Duration of protocol therapy, which could be up to about 1 year Only eligible patients that received at least one dose of protocol therapy are included for Adverse event reporting (there were 2 ineligible patients on Stratum 1 (27 at risk) and 2 ineligible patients on Stratum 2 (28 at risk).
Metabolism and nutrition disorders Hyponatremia: Sodium, serum-low (hyponatremia)	11.1% 3/27 • Duration of protocol therapy, which could be up to about 1 year Only eligible patients that received at least one dose of protocol therapy are included for Adverse event reporting (there were 2 ineligible patients on Stratum 1 (27 at risk) and 2 ineligible patients on Stratum 2 (28 at risk).	14.3% 4/28 • Duration of protocol therapy, which could be up to about 1 year Only eligible patients that received at least one dose of protocol therapy are included for Adverse event reporting (there were 2 ineligible patients on Stratum 1 (27 at risk) and 2 ineligible patients on Stratum 2 (28 at risk).
Investigations Leukocytes (total WBC)	37.0% 10/27 • Duration of protocol therapy, which could be up to about 1 year Only eligible patients that received at least one dose of protocol therapy are included for Adverse event reporting (there were 2 ineligible patients on Stratum 1 (27 at risk) and 2 ineligible patients on Stratum 2 (28 at risk).	25.0% 7/28 • Duration of protocol therapy, which could be up to about 1 year Only eligible patients that received at least one dose of protocol therapy are included for Adverse event reporting (there were 2 ineligible patients on Stratum 1 (27 at risk) and 2 ineligible patients on Stratum 2 (28 at risk).
Investigations Lymphopenia	14.8% 4/27 • Duration of protocol therapy, which could be up to about 1 year Only eligible patients that received at least one dose of protocol therapy are included for Adverse event reporting (there were 2 ineligible patients on Stratum 1 (27 at risk) and 2 ineligible patients on Stratum 2 (28 at risk).	10.7% 3/28 • Duration of protocol therapy, which could be up to about 1 year Only eligible patients that received at least one dose of protocol therapy are included for Adverse event reporting (there were 2 ineligible patients on Stratum 1 (27 at risk) and 2 ineligible patients on Stratum 2 (28 at risk).
Gastrointestinal disorders Nausea	0.00% 0/27 • Duration of protocol therapy, which could be up to about 1 year Only eligible patients that received at least one dose of protocol therapy are included for Adverse event reporting (there were 2 ineligible patients on Stratum 1 (27 at risk) and 2 ineligible patients on Stratum 2 (28 at risk).	10.7% 3/28 • Duration of protocol therapy, which could be up to about 1 year Only eligible patients that received at least one dose of protocol therapy are included for Adverse event reporting (there were 2 ineligible patients on Stratum 1 (27 at risk) and 2 ineligible patients on Stratum 2 (28 at risk).
Investigations Neutrophils/granulocytes (ANC/AGC)	48.1% 13/27 • Duration of protocol therapy, which could be up to about 1 year Only eligible patients that received at least one dose of protocol therapy are included for Adverse event reporting (there were 2 ineligible patients on Stratum 1 (27 at risk) and 2 ineligible patients on Stratum 2 (28 at risk).	28.6% 8/28 • Duration of protocol therapy, which could be up to about 1 year Only eligible patients that received at least one dose of protocol therapy are included for Adverse event reporting (there were 2 ineligible patients on Stratum 1 (27 at risk) and 2 ineligible patients on Stratum 2 (28 at risk).
Gastrointestinal disorders Pain - Abdomen NOS	7.4% 2/27 • Duration of protocol therapy, which could be up to about 1 year Only eligible patients that received at least one dose of protocol therapy are included for Adverse event reporting (there were 2 ineligible patients on Stratum 1 (27 at risk) and 2 ineligible patients on Stratum 2 (28 at risk).	7.1% 2/28 • Duration of protocol therapy, which could be up to about 1 year Only eligible patients that received at least one dose of protocol therapy are included for Adverse event reporting (there were 2 ineligible patients on Stratum 1 (27 at risk) and 2 ineligible patients on Stratum 2 (28 at risk).
Musculoskeletal and connective tissue disorders Pain - Extremity-limb	14.8% 4/27 • Duration of protocol therapy, which could be up to about 1 year Only eligible patients that received at least one dose of protocol therapy are included for Adverse event reporting (there were 2 ineligible patients on Stratum 1 (27 at risk) and 2 ineligible patients on Stratum 2 (28 at risk).	7.1% 2/28 • Duration of protocol therapy, which could be up to about 1 year Only eligible patients that received at least one dose of protocol therapy are included for Adverse event reporting (there were 2 ineligible patients on Stratum 1 (27 at risk) and 2 ineligible patients on Stratum 2 (28 at risk).
Nervous system disorders Pain - Head/headache	7.4% 2/27 • Duration of protocol therapy, which could be up to about 1 year Only eligible patients that received at least one dose of protocol therapy are included for Adverse event reporting (there were 2 ineligible patients on Stratum 1 (27 at risk) and 2 ineligible patients on Stratum 2 (28 at risk).	0.00% 0/28 • Duration of protocol therapy, which could be up to about 1 year Only eligible patients that received at least one dose of protocol therapy are included for Adverse event reporting (there were 2 ineligible patients on Stratum 1 (27 at risk) and 2 ineligible patients on Stratum 2 (28 at risk).
Investigations Platelets	25.9% 7/27 • Duration of protocol therapy, which could be up to about 1 year Only eligible patients that received at least one dose of protocol therapy are included for Adverse event reporting (there were 2 ineligible patients on Stratum 1 (27 at risk) and 2 ineligible patients on Stratum 2 (28 at risk).	10.7% 3/28 • Duration of protocol therapy, which could be up to about 1 year Only eligible patients that received at least one dose of protocol therapy are included for Adverse event reporting (there were 2 ineligible patients on Stratum 1 (27 at risk) and 2 ineligible patients on Stratum 2 (28 at risk).
Gastrointestinal disorders Vomiting	0.00% 0/27 • Duration of protocol therapy, which could be up to about 1 year Only eligible patients that received at least one dose of protocol therapy are included for Adverse event reporting (there were 2 ineligible patients on Stratum 1 (27 at risk) and 2 ineligible patients on Stratum 2 (28 at risk).	10.7% 3/28 • Duration of protocol therapy, which could be up to about 1 year Only eligible patients that received at least one dose of protocol therapy are included for Adverse event reporting (there were 2 ineligible patients on Stratum 1 (27 at risk) and 2 ineligible patients on Stratum 2 (28 at risk).