A Phase 2 interventional study of irinotecan hydrochloride and temozolomide in Neuroblastoma, sponsored by Children's Oncology Group. Completed at 128 sites in 3 countries. Open to participants aged Up to 21 Years. Per ClinicalTrials.gov, last updated 2014-09-30.
Sponsored by Children's Oncology Group · Phase 2, Interventional, and Treatment
RATIONALE: Drugs used in chemotherapy, such as irinotecan and temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving irinotecan together with temozolomide works in treating young patients with recurrent neuroblastoma.
OBJECTIVES:
Primary
Secondary
OUTLINE: This is a multicenter study.
Patients are stratified according to disease status (measurable disease [measured by conventional CT scan and/or MRI] vs evaluable disease [tumor detected by conventional morphologic analysis of bone marrow aspirate/biopsy AND/OR abnormal uptake at ≥ 1 site on MIBG scan]).
Patients receive irinotecan hydrochloride IV over 1 hour on days 1-5 and 8-12 and oral temozolomide on days 1-5. Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed periodically for up to 10 years.
PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.
625 studies on the registry are indexed under Neuroblastoma; 122 are open to participants now.
This study's enrollment of 59 is above the median of 32 across 475 interventional studies indexed under Neuroblastoma.
Browse Neuroblastoma studies →Children's Oncology Group is the lead sponsor of 436 studies on the registry; 34 are open to participants now.
Of its 12 completed or terminated interventional studies of FDA-regulated products, 11 (92%) have results posted.
Counted across the registry records on this site, refreshed daily.
DISEASE CHARACTERISTICS:
Histologically confirmed neuroblastoma AND/OR demonstration of tumor cells in the bone marrow with increased urinary catecholamines at initial diagnosis
Meets 1 of the following criteria:
Must meet 1 of the following criteria for documentation of disease:
Unidimensionally measurable tumor ≥ 20 mm by MRI (Magnetic Resonance Imaging), CT scan (Computed Tomography), or x-ray OR ≥ 10 mm by spiral CT scan within 4 weeks prior to study entry
MIBG scan (metaiodobenzylguanidine scan, a radiopharmaceutical) with positive uptake at ≥ 1 site within 4 weeks prior to study entry
PATIENT CHARACTERISTICS:
Creatinine adjusted according to age as follows:
PRIOR CONCURRENT THERAPY:
At least 1 week since prior and no concurrent enzyme-inducing anticonvulsants (EIAC), including phenytoin, phenobarbital, valproic acid, or carbamazepine
No prior allogeneic stem cell transplantation (SCT)
No concurrent immunomodulating agents
Measurable by CT scan (Computed Tomography) or MRI scan (Magnetic Resonance Imaging). 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.
Drug: irinotecan hydrochloride · Drug: 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.
Drug: irinotecan hydrochloride · Drug: temozolomide
Given IV
Also known as: CPT-11, NSC #616348
Given IV
Also known as: TEMODAR, NSC #362856
Overall Response - Complete Response (CR), Very Good Partial Response (VGPR) and Partial Response (PR)
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).
Time frame: up to 6 courses of therapy, or about 6 months
| Milestone | Disease Eval by Bone Marrow or MIBG (Irinotecan/Temozolomide) | Disease Measurable by CT or MRI Scan (Irinotecan/Temozolomide) |
|---|---|---|
| Started | 29 | 30 |
| Completed | 9 | 7 |
| Not completed | 20 | 23 |
| Withdrew: Death | 1 | 0 |
| Withdrew: Lack of efficacy | 12 | 15 |
| Withdrew: Physician decision | 4 | 5 |
| Withdrew: Withdrawal by subject | 1 | 1 |
| Withdrew: Ineligible | 2 | 2 |
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).
| participants | Disease Eval by Bone Marrow or MIBG (Irinotecan/Temozolomide) | Disease Measurable by CT or MRI Scan (Irinotecan/Temozolomide) |
|---|---|---|
| Overall Response - Complete Response (CR), Very Good Partial Response (VGPR) and Partial Response (PR) | 5 | 3 |
Collected over Duration of protocol therapy, which could be up to about 1 year. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Disease Eval by Bone Marrow or MIBG (Irinotecan/Temozolomide) | — | 0/27 (0%) | 13/27 (48.1%) |
| Disease Measurable by CT or MRI Scan (Irinotecan/Temozolomide) | — | 1/28 (3.6%) | 8/28 (28.6%) |
| Event | Disease Eval by Bone Marrow or MIBG (Irinotecan/Temozolomide) | Disease Measurable by CT or MRI Scan (Irinotecan/Temozolomide) |
|---|---|---|
| Death not associated with CTCAE term - Disease progression NOSGeneral disorders | 0/27 | 1/28 |
| Event | Disease Eval by Bone Marrow or MIBG (Irinotecan/Temozolomide) | Disease Measurable by CT or MRI Scan (Irinotecan/Temozolomide) |
|---|---|---|
| Neutrophils/granulocytes (ANC/AGC)Investigations | 13/27 | 8/28 |
| Leukocytes (total WBC)Investigations | 10/27 | 7/28 |
| HemoglobinBlood and lymphatic system disorders | 7/27 | 7/28 |
| PlateletsInvestigations | 7/27 | 3/28 |
| Hyperglycemia: Glucose, serum-high (hyperglycemia)Metabolism and nutrition disorders | 6/27 | 2/28 |
| AST: AST, SGOT(serum glutamic oxaloacetic transaminase)Investigations | 4/27 | 2/28 |
| Hypokalemia: Potassium, serum-low (hypokalemia)Metabolism and nutrition disorders | 4/27 | 2/28 |
| LymphopeniaInvestigations | 4/27 | 3/28 |
| Pain - Extremity-limbMusculoskeletal and connective tissue disorders | 4/27 | 2/28 |
| Hyponatremia: Sodium, serum-low (hyponatremia)Metabolism and nutrition disorders | 3/27 | 4/28 |
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.
| Age, Categorical(Participants) | Disease Eval by Bone Marrow or MIBG (Irinotecan/Temozolomide) | Disease Measurable by CT or MRI Scan (Irinotecan/Temozolomide) | Total |
|---|---|---|---|
| <=18 years | 28 | 30 | 58 |
| Between 18 and 65 years | 1 | 0 | 1 |
| >=65 years | 0 | 0 | 0 |
| Age, Continuous(days) | Disease Eval by Bone Marrow or MIBG (Irinotecan/Temozolomide) | Disease Measurable by CT or MRI Scan (Irinotecan/Temozolomide) | Total |
|---|---|---|---|
| Median | 1922 (1682 to 2827) | 1562 (1158 to 2648.5) | 1742 (1420 to 2737.75) |
| Sex: Female, Male(Participants) | Disease Eval by Bone Marrow or MIBG (Irinotecan/Temozolomide) | Disease Measurable by CT or MRI Scan (Irinotecan/Temozolomide) | Total |
|---|---|---|---|
| Female | 15 | 11 | 26 |
| Male | 14 | 19 | 33 |
| Ethnicity (NIH/OMB)(Participants) | Disease Eval by Bone Marrow or MIBG (Irinotecan/Temozolomide) | Disease Measurable by CT or MRI Scan (Irinotecan/Temozolomide) | Total |
|---|---|---|---|
| Hispanic or Latino | 0 | 4 | 4 |
| Not Hispanic or Latino | 26 | 22 | 48 |
| Unknown or Not Reported | 3 | 4 | 7 |
| Race (NIH/OMB)(Participants) | Disease Eval by Bone Marrow or MIBG (Irinotecan/Temozolomide) | Disease Measurable by CT or MRI Scan (Irinotecan/Temozolomide) | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 3 | 3 |
| Native Hawaiian or Other Pacific Islander | 1 | 0 | 1 |
| Black or African American | 4 | 2 | 6 |
| White | 20 | 21 | 41 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 4 | 4 | 8 |
| Region of Enrollment(participants) | Disease Eval by Bone Marrow or MIBG (Irinotecan/Temozolomide) | Disease Measurable by CT or MRI Scan (Irinotecan/Temozolomide) | Total |
|---|---|---|---|
| United States | 26 | 28 | 54 |
| Canada | 2 | 2 | 4 |
| Australia | 1 | 0 | 1 |
Showing the first 100 of 128 sites across 3 countries.
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