NeuroblastomaPhase 1/2NCT01601535
Study of MLN8237 in Combination With Irinotecan and Temozolomide
A Phase 1/2 study testing MLN8237, Irinotecan and Temozolomide in people with Neuroblastoma, run by New Approaches to Neuroblastoma Therapy Consortium at 13 sites in 2 countries.
Trial summary
The goal of the first part of this clinical trial (Phase I portion) is to study the side effects, drug breakdown (pharmacokinetics), and dosing of the drug MLN8237 when added to standard chemotherapy drugs, irinotecan and temozolomide. Read more about this study
- Who is it for?
- Ages 12 months to 30 years
- Conditions the study is for
- Neuroblastoma
- What is being tested?
- MLN8237, Irinotecan and Temozolomide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- 13 sitesin 2 countries
- Study dates
- May 2012to 25 Jul 2018
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 months to 30 years
- All sexes
- No healthy volunteers
- Child, Adult
Criteria that need to be met to participate in this study:
- Patients must be > 12 months and < 30 years of age when registered on study.
- Patients must have relapsed neuroblastoma, refractory neuroblastoma that had less than a partial response to standard treatment or persistent neuroblastoma that had at least a partial response to standard treatment. All patients must have at least ONE site of evaluable disease.
- Patients who have at least a partial response to standard treatment who still have neuroblastoma that can be seen on CT/MRI or MIBG scans must have a surgical biopsy done of the tumor to confirm that it is neuroblastoma. Patients with relapsed or refractory neuroblastoma do not need to have a biopsy done to enter on study.
- Patients must have adequate heart, kidney, liver and bone marrow function. Patients who have bone marrow disease must still have adequate bone marrow function to enter the study.
- MLN8237 must be swallowed as whole tablets. Therefore, patients must be able to swallow pills to be eligible for study. One tablet is the size of small breath mint, or baby aspirin. Due to the size of MLN8237 tablets, patients must have a body surface area of at least 0.38 m2 to be eligible for study. A body surface area is a combination of a patient's height and weight. An example of a child with a BSA of 0.45 is a child that is 25 inches tall and weighs 25 pounds.You can use the link below to calculate your child's body surface area and determine if they are too small for this trial.
Patients cannot participate in the study if:
- Patients who have received prior MLN8237 are excluded from all phases of the study. Patients previously treated with irinotecan and/or temozolomide will be eligible if they have not had documented progressive disease during treatment with a regimen containing these agents.
- They have other medical problems that could get much worse if they had this treatment.
- They are on dialysis for bad kidney function.
- They are pregnant or breast feeding.
- They have active infections such as hepatitis or fungal infections.
- They have an allergy to treatment with cefixime and cefpodixime.
- They have brain metastasis at study entry, or have received cranial spinal radiation.
- They have had an allogeneic stem cell transplant (received stem cell from someone else).
- They can't cooperate with the special precautions that are needed for this trial.
Trial locations and contacts
13 sites in 2 countries.
13 sites in 2 countries
United States12 sites
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109
Children's Healthcare of Atlanta
Atlanta, Georgia, 30322
Children Hospital of Colorado
Aurora, Colorado, 80045
Childrens Hospital Boston, Dana-Farber Cancer Institute.
Boston, Massachusetts, 02115
University of Chicago Comer Children's Hospital
Chicago, Illinois, 60637
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229-3039
Cook Children's Medical Center - Fort Worth
Fort Worth, Texas, 76104
Children's Hospital Los Angeles
Los Angeles, California, 90027-0700
Lucile Packard Children's Hospital at Stanford University Medical Center
Palo Alto, California, 94304
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104-4318
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, 94115
Children's Hospital and Regional Medical Center - Seattle
Seattle, Washington, 98105
About this study
Official title: Phase I/II Study of MLN8237 in Combination With Irinotecan and Temozolomide for Patients With Relapsed or Refractory Neuroblastoma
The goal of the first part of this clinical trial (Phase I portion) is to study the side effects, drug breakdown (pharmacokinetics), and dosing of the drug MLN8237 when added to standard chemotherapy drugs, irinotecan and temozolomide.
The goal of the second part of this clinical trial (Phase II portion) is to learn how many children and young adults show improvements in their neuroblastoma when treated with the combination of MLN8237, irinotecan, and temozolomide.
Read the detailed description
The Aurora A kinase has been shown to play an important role in neuroblastoma growth. Inhibition of Aurora A kinase activity attenuates the growth of neuroblastoma cells. MLN8237 is a selective small molecule inhibitor of Aurora A kinase that has completed pediatric single-agent phase I testing, as well as stage 1 phase 2 testing in patients with Neuroblastoma. MLN8237 showed activity against the NCI-sponsored Pediatric Preclinical Testing Program neuroblastoma in vivo panel that exceeded the activity level observed with chemotherapy agents routinely used in the treatment of neuroblastoma. Additional in vitro and in vivo studies have shown that Aurora A kinase inhibitors result in enhanced cytotoxicity when used in combination with chemotherapy. Irinotecan and temozolomide is a commonly used salvage regimen for patients with relapsed or refractory neuroblastoma. This combination has a modest objective response rate (16%) and is well-tolerated, suggesting that it will provide a useful platform for the study of novel compounds in combination with chemotherapy. Preclinical studies demonstrate marked enhancement of anti-neuroblastoma activity with the addition of MLN8237 to irinotecan and temozolomide. This study therefore evaluates the tolerability and activity of MLN8237 in combination with irinotecan and temozolomide in children with refractory or relapsed neuroblastoma. Patients receive irinotecan (50 mg/m2/dose IV) and temozolomide (100 mg/m2/dose orally) once daily for 5 days along with MLN8237 orally once daily for 7 days. The doses of irinotecan and temozolomide will be fixed and the dose of MLN8237 will be dose-escalated. In the phase I portion of the study, the primary aims are to determine the recommended phase II doses of this combination, describe the toxicity of this combination, and characterize the pharmacokinetic profile of MLN8237 and irinotecan when used in combination. In the phase II portion of the study, the primary aim is to determine the objective response rate of this combination in patients with relapsed or refractory neuroblastoma. With Amendment 5, the tolerability and pharmacokinetics of an MLN8237 oral solution will be evaluated. Optional correlative studies will evaluate UGT1A1 polymorphisms as predictors of toxicity and archival tumor tissue Aurora A expression as a predictor of response with this combination.
- Conditions
- Neuroblastoma
- Being tested
- MLN8237, Irinotecan, Temozolomide
- Medical subject headings
- Neuroblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MLN8237Drug
Every course will be 21 days. MLN8237 will be administered orally daily starting on day 1 through day 7.
IrinotecanDrug
Also called Camptosar
Irinotecan will be administered intravenously during each course on study day 1 through day 5.
TemozolomideDrug
Also called Temodar
Temozolomide will be administered orally during each course on study day 1 through day 5.
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | Every course will be 21 days. MLN8237 will be administered orally daily starting on day 1 through day 7.
Irinotecan will be administered intravenously during each course on study day 1 through day 5.
Temozolomide will be administered orally during each course on study day 1 through day 5. Receives: Drug: MLN8237; Drug: Irinotecan; Drug: Temozolomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) When Given Together With Fixed Doses of Irinotecan and Temozolomide in Children and Young Adults With Relapsed or Refractory Neuroblastoma
The MTD was the highest dose level tested at which fewer than two of six patients had first course DLT. Hematologic DLT was defined as grade 4 neutropenia for more than 7 days, need for platelet transfusion for a platelet count of less than 20,000/mL twice within a 7-day period, or greater than 14-day delay in the start of a subsequent course because of neutropenia or thrombocytopenia. Nonhematologic DLT was defined as any nonhematologic toxicity that delayed the start of a subsequent cycle by more than 14 days or any grade ≥3 toxicity with the exception of the following grade 3 toxicities: nausea, vomiting, anorexia, or dehydration resolving to grade ≤ 2 within 72 hours; increase in hepatic transaminase or electrolyte abnormality resolving to grade ≤ 1 within 7 days; diarrhea persisting for less than 72 hours; fever; infection; or febrile neutropenia. DLT definitions included only toxicities deemed at least possibly related to therapy.
Measured: 21 days, from study day 1
Dose Limiting Toxicity (DLT) Data Associated With the Determination of the Recommended Phase 2 Dose
The MTD was the highest dose level tested at which fewer than two of six patients had first course DLT. Hematologic DLT was defined as grade 4 neutropenia for more than 7 days, need for platelet transfusion for a platelet count of less than 20,000/mL twice within a 7-day period, or greater than 14-day delay in the start of a subsequent course because of neutropenia or thrombocytopenia. Nonhematologic DLT was defined as any nonhematologic toxicity that delayed the start of a subsequent cycle by more than 14 days or any grade ≥3 toxicity with the exception of the following grade 3 toxicities: nausea, vomiting, anorexia, or dehydration resolving to grade ≤ 2 within 72 hours; increase in hepatic transaminase or electrolyte abnormality resolving to grade ≤ 1 within 7 days; diarrhea persisting for less than 72 hours; fever; infection; or febrile neutropenia. DLT definitions included only toxicities deemed at least possibly related to therapy.
Measured: 21 days, from study day 1
Pharmacokinetics When Given Together With Fixed Doses of Irinotecan and Temozolomide in Children and Young Adults With Relapsed or Refractory Neuroblastoma: Alisertib Day 4 Trough, Day 5 Trough and Cmax
Outcomes included Alisertib, irinotecan, APC, SN-38, and SN-38G. APC, SN-38, and SN-38G are metabolites of irinotecan.
Measured: 1st week of cycle 1
Pharmacokinetics When Given Together With Fixed Doses of Irinotecan and Temozolomide in Children and Young Adults With Relapsed or Refractory Neuroblastoma: Alisertib Tmax and Half-life
Outcomes included Alisertib, irinotecan, APC, SN-38, and SN-38G. APC, SN-38, and SN-38G are metabolites of irinotecan.
Measured: 1st week of cycle 1
Pharmacokinetics When Given Together With Fixed Doses of Irinotecan and Temozolomide in Children and Young Adults With Relapsed or Refractory Neuroblastoma: Alisertib AUC
Outcomes included Alisertib, irinotecan, APC, SN-38, and SN-38G. APC, SN-38, and SN-38G are metabolites of irinotecan.
Measured: 1st week of cycle 1
Pharmacokinetics When Given Together With Fixed Doses of Irinotecan and Temozolomide in Children and Young Adults With Relapsed or Refractory Neuroblastoma: Irinotecan Cmax, APC Cmax, SN-38 Cmax, and SN-38G Cmax
Outcomes included Alisertib, irinotecan, APC, SN-38, and SN-38G. APC, SN-38, and SN-38G are metabolites of irinotecan.
Measured: 1st week of cycle 1
Pharmacokinetics When Given Together With Fixed Doses of Irinotecan and Temozolomide in Children and Young Adults With Relapsed or Refractory Neuroblastoma: Irinotecan AUC, APC AUC, SN-38 AUC, and SN-38G AUC
Outcomes included Alisertib, irinotecan, APC, SN-38, and SN-38G. APC, SN-38, and SN-38G are metabolites of irinotecan.
Measured: 1st week of cycle 1
Pharmacokinetics When Given Together With Fixed Doses of Irinotecan and Temozolomide in Children and Young Adults With Relapsed or Refractory Neuroblastoma: Irinotecan Clearance
Outcomes included Alisertib, irinotecan, APC, SN-38, and SN-38G. APC, SN-38, and SN-38G are metabolites of irinotecan.
Measured: 1st week of cycle 1
Response Rate for Patients With Relapsed or Refractory Neuroblastoma Treated With MLN8237, Irinotecan, and Temozolomide at the Identified MTD
Response was graded according to version 1.2 of the NANT response criteria that classifies patients as having one of the following overall response categories based upon underlying response at soft tissue sites, MIBG positive sites, and bone marrow disease: complete response (CR); CR with minimal residual disease (CR-MRD); partial response (PR); minor response (MR); stable disease (SD); and progressive disease (PD). These criteria utilize RECIST criteria for measurable tumors, Curie score for MIBG scan response, and bone marrow (BM) morphology. BM response was graded as CR (required two time points to confirm), CR unconfirmed (one time point only), CR-MRD (bone marrow involvement < 5% at study entry with negative follow-up biopsies), SD, or PD. Patients with at least SD or better underwent central review of MIBG scans, CT scans, and bone marrow pathology slides. Overall responses of CR, CR-MRD, or PR were considered objective responses.
Measured: Cycles repeated every 21 days for up to 34 cycles.
Secondary outcomes (4)
Aurora A Expression
To explore whether MYCN status and markers of expression of Aurora A in archival tumor tissue are associated with the antitumor activity of the combination of MLN8237, irinotecan, and temozolomide
Measured: From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
UGT1A1 Genotype
To explore whether UGT1A1 genotype is associated with toxicity in children with refractory neuroblastoma treated with the combination of MLN8237, irinotecan, and temozolomide
Measured: Day 7 of cycle 1
AURKA Genotype
To explore whether AURKA genotype is associated with antitumor activity in children with refractory neuroblastoma treated with the combination of MLN8237, irinotecan, and temozolomide.
Measured: Day 7 of cycle 1
One Year Progression Free Survival Rate
To determine the progression free survival rates for patients with relapsed or refractory neuroblastoma treated with MLN8237, irinotecan, and temozolomide at the identified MTD
Measured: 1 Years after completion of study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2012 (estimated)
- Study startMay 2012
- Primary completion25 Jul 2018
- Study completion25 Jul 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for NeuroblastomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Lead sponsor
- New Approaches to Neuroblastoma Therapy Consortium
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Steven DuBois, MD, Study chair, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01601535
- Sponsor's protocol ID
- N2009-03
- Status last verified
- Jul 2019
- First submitted
- 11 May 2012
- Last updated
- 31 Jul 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
DuBois SG, Mosse YP, Fox E, Kudgus RA, Reid JM, McGovern R, Groshen S, Bagatell R, Maris JM, Twist CJ, Goldsmith K, Granger MM, Weiss B, Park JR, Macy ME, Cohn SL, Yanik G, Wagner LM, Hawkins R, Courtier J, Lai H, Goodarzian F, Shimada H, Boucher N, Czarnecki S, Luo C, Tsao-Wei D, Matthay KK, Marachelian A. Phase II Trial of Alisertib in Combination with Irinotecan and Temozolomide for Patients with Relapsed or Refractory Neuroblastoma. Clin Cancer Res. 2018 Dec 15;24(24):6142-6149. doi: 10.1158/1078-0432.CCR-18-1381. Epub 2018 Aug 9.
PubMed 30093449
Study at a glance
From the registry record, last updated by the sponsor on 31 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Study of MLN8237 in Combination With Irinotecan and Temozolomide for Patients With Relapsed or Refractory Neuroblastoma
- ClinicalTrials.gov ID
- NCT01601535
- Acronym / sponsor ID
- N2009-03
- Conditions
- Neuroblastoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 54 participants (actual)
- Lead sponsor
- New Approaches to Neuroblastoma Therapy ConsortiumUniversity, hospital or other
- Study start
- May 2012
- Primary completion
- 25 Jul 2018 (actual)
- Study completion
- 25 Jul 2018 (actual)
- First posted
- 18 May 2012 (estimated)
- Results
- Posted 31 Jul 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of the first part of this clinical trial (Phase I portion) is to study the side effects, drug breakdown (pharmacokinetics), and dosing of the drug MLN8237 when added to standard chemotherapy drugs, irinotecan and temozolomide.
The goal of the second part of this clinical trial (Phase II portion) is to learn how many children and young adults show improvements in their neuroblastoma when treated with the combination of MLN8237, irinotecan, and temozolomide.
Detailed description
The Aurora A kinase has been shown to play an important role in neuroblastoma growth. Inhibition of Aurora A kinase activity attenuates the growth of neuroblastoma cells. MLN8237 is a selective small molecule inhibitor of Aurora A kinase that has completed pediatric single-agent phase I testing, as well as stage 1 phase 2 testing in patients with Neuroblastoma. MLN8237 showed activity against the NCI-sponsored Pediatric Preclinical Testing Program neuroblastoma in vivo panel that exceeded the activity level observed with chemotherapy agents routinely used in the treatment of neuroblastoma. Additional in vitro and in vivo studies have shown that Aurora A kinase inhibitors result in enhanced cytotoxicity when used in combination with chemotherapy. Irinotecan and temozolomide is a commonly used salvage regimen for patients with relapsed or refractory neuroblastoma. This combination has a modest objective response rate (16%) and is well-tolerated, suggesting that it will provide a useful platform for the study of novel compounds in combination with chemotherapy. Preclinical studies demonstrate marked enhancement of anti-neuroblastoma activity with the addition of MLN8237 to irinotecan and temozolomide. This study therefore evaluates the tolerability and activity of MLN8237 in combination with irinotecan and temozolomide in children with refractory or relapsed neuroblastoma. Patients receive irinotecan (50 mg/m2/dose IV) and temozolomide (100 mg/m2/dose orally) once daily for 5 days along with MLN8237 orally once daily for 7 days. The doses of irinotecan and temozolomide will be fixed and the dose of MLN8237 will be dose-escalated. In the phase I portion of the study, the primary aims are to determine the recommended phase II doses of this combination, describe the toxicity of this combination, and characterize the pharmacokinetic profile of MLN8237 and irinotecan when used in combination. In the phase II portion of the study, the primary aim is to determine the objective response rate of this combination in patients with relapsed or refractory neuroblastoma. With Amendment 5, the tolerability and pharmacokinetics of an MLN8237 oral solution will be evaluated. Optional correlative studies will evaluate UGT1A1 polymorphisms as predictors of toxicity and archival tumor tissue Aurora A expression as a predictor of response with this combination.
Study design
- Primary purpose
- Treatment
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Drug: MLN8237, Drug: Irinotecan, Drug: TemozolomideEvery course will be 21 days. MLN8237 will be administered orally daily starting on day 1 through day 7. Irinotecan will be administered intravenously during each course on study day 1 through day 5. Temozolomide will be administered orally during each course on study day 1 through day 5. |
Who may qualify
- Ages
- 12 months to 30 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MLN8237Every course will be 21 days. MLN8237 will be administered orally daily starting on day 1 through day 7. | Drug | Treatment |
| IrinotecanAlso: CamptosarIrinotecan will be administered intravenously during each course on study day 1 through day 5. | Drug | Treatment |
| TemozolomideAlso: TemodarTemozolomide will be administered orally during each course on study day 1 through day 5. | Drug | Treatment |
Primary outcome
Maximum Tolerated Dose (MTD) When Given Together With Fixed Doses of Irinotecan and Temozolomide in Children and Young Adults With Relapsed or Refractory Neuroblastoma
Time frame: 21 days, from study day 1
The MTD was the highest dose level tested at which fewer than two of six patients had first course DLT. Hematologic DLT was defined as grade 4 neutropenia for more than 7 days, need for platelet transfusion for a platelet count of less than 20,000/mL twice within a 7-day period, or greater than 14-day delay in the start of a subsequent course because of neutropenia or thrombocytopenia. Nonhematologic DLT was defined as any nonhematologic toxicity that delayed the start of a subsequent cycle by more than 14 days or any grade ≥3 toxicity with the exception of the following grade 3 toxicities: nausea, vomiting, anorexia, or dehydration resolving to grade ≤ 2 within 72 hours; increase in hepatic transaminase or electrolyte abnormality resolving to grade ≤ 1 within 7 days; diarrhea persisting for less than 72 hours; fever; infection; or febrile neutropenia. DLT definitions included only toxicities deemed at least possibly related to therapy.
Dose Limiting Toxicity (DLT) Data Associated With the Determination of the Recommended Phase 2 Dose
Time frame: 21 days, from study day 1
The MTD was the highest dose level tested at which fewer than two of six patients had first course DLT. Hematologic DLT was defined as grade 4 neutropenia for more than 7 days, need for platelet transfusion for a platelet count of less than 20,000/mL twice within a 7-day period, or greater than 14-day delay in the start of a subsequent course because of neutropenia or thrombocytopenia. Nonhematologic DLT was defined as any nonhematologic toxicity that delayed the start of a subsequent cycle by more than 14 days or any grade ≥3 toxicity with the exception of the following grade 3 toxicities: nausea, vomiting, anorexia, or dehydration resolving to grade ≤ 2 within 72 hours; increase in hepatic transaminase or electrolyte abnormality resolving to grade ≤ 1 within 7 days; diarrhea persisting for less than 72 hours; fever; infection; or febrile neutropenia. DLT definitions included only toxicities deemed at least possibly related to therapy.
Pharmacokinetics When Given Together With Fixed Doses of Irinotecan and Temozolomide in Children and Young Adults With Relapsed or Refractory Neuroblastoma: Alisertib Day 4 Trough, Day 5 Trough and Cmax
Time frame: 1st week of cycle 1
Outcomes included Alisertib, irinotecan, APC, SN-38, and SN-38G. APC, SN-38, and SN-38G are metabolites of irinotecan.
Pharmacokinetics When Given Together With Fixed Doses of Irinotecan and Temozolomide in Children and Young Adults With Relapsed or Refractory Neuroblastoma: Alisertib Tmax and Half-life
Time frame: 1st week of cycle 1
Outcomes included Alisertib, irinotecan, APC, SN-38, and SN-38G. APC, SN-38, and SN-38G are metabolites of irinotecan.
Pharmacokinetics When Given Together With Fixed Doses of Irinotecan and Temozolomide in Children and Young Adults With Relapsed or Refractory Neuroblastoma: Alisertib AUC
Time frame: 1st week of cycle 1
Outcomes included Alisertib, irinotecan, APC, SN-38, and SN-38G. APC, SN-38, and SN-38G are metabolites of irinotecan.
Pharmacokinetics When Given Together With Fixed Doses of Irinotecan and Temozolomide in Children and Young Adults With Relapsed or Refractory Neuroblastoma: Irinotecan Cmax, APC Cmax, SN-38 Cmax, and SN-38G Cmax
Time frame: 1st week of cycle 1
Outcomes included Alisertib, irinotecan, APC, SN-38, and SN-38G. APC, SN-38, and SN-38G are metabolites of irinotecan.
Pharmacokinetics When Given Together With Fixed Doses of Irinotecan and Temozolomide in Children and Young Adults With Relapsed or Refractory Neuroblastoma: Irinotecan AUC, APC AUC, SN-38 AUC, and SN-38G AUC
Time frame: 1st week of cycle 1
Outcomes included Alisertib, irinotecan, APC, SN-38, and SN-38G. APC, SN-38, and SN-38G are metabolites of irinotecan.
Pharmacokinetics When Given Together With Fixed Doses of Irinotecan and Temozolomide in Children and Young Adults With Relapsed or Refractory Neuroblastoma: Irinotecan Clearance
Time frame: 1st week of cycle 1
Outcomes included Alisertib, irinotecan, APC, SN-38, and SN-38G. APC, SN-38, and SN-38G are metabolites of irinotecan.
Response Rate for Patients With Relapsed or Refractory Neuroblastoma Treated With MLN8237, Irinotecan, and Temozolomide at the Identified MTD
Time frame: Cycles repeated every 21 days for up to 34 cycles.
Response was graded according to version 1.2 of the NANT response criteria that classifies patients as having one of the following overall response categories based upon underlying response at soft tissue sites, MIBG positive sites, and bone marrow disease: complete response (CR); CR with minimal residual disease (CR-MRD); partial response (PR); minor response (MR); stable disease (SD); and progressive disease (PD). These criteria utilize RECIST criteria for measurable tumors, Curie score for MIBG scan response, and bone marrow (BM) morphology. BM response was graded as CR (required two time points to confirm), CR unconfirmed (one time point only), CR-MRD (bone marrow involvement < 5% at study entry with negative follow-up biopsies), SD, or PD. Patients with at least SD or better underwent central review of MIBG scans, CT scans, and bone marrow pathology slides. Overall responses of CR, CR-MRD, or PR were considered objective responses.
4 secondary outcomes
Aurora A Expression
Time frame: From date of study enrollment to the date of progression or withdrawal from the study, up to 34 cycles (about 2 years).
UGT1A1 Genotype
Time frame: Day 7 of cycle 1
AURKA Genotype
Time frame: Day 7 of cycle 1
One Year Progression Free Survival Rate
Time frame: 1 Years after completion of study
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30093449DuBois SG, Mosse YP, Fox E, Kudgus RA, Reid JM, McGovern R, Groshen S, Bagatell R, Maris JM, Twist CJ, Goldsmith K, Granger MM, Weiss B, Park JR, Macy ME, Cohn SL, Yanik G, Wagner LM, Hawkins R, Courtier J, Lai H, Goodarzian F, Shimada H, Boucher N, Czarnecki S, Luo C, Tsao-Wei D, Matthay KK, Marachelian A. Phase II Trial of Alisertib in Combination with Irinotecan and Temozolomide for Patients with Relapsed or Refractory Neuroblastoma. Clin Cancer Res. 2018 Dec 15;24(24):6142-6149. doi: 10.1158/1078-0432.CCR-18-1381. Epub 2018 Aug 9.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Steven DuBois, MD study chair
Dana-Farber Cancer Institute
13 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing MLN8237, Irinotecan and Temozolomide in people with Neuroblastoma, run by New Approaches to Neuroblastoma Therapy Consortium at 13 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 31 Jul 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerated Dose (MTD) When Given Together With Fixed Doses of Irinotecan and Temozolomide in Children and Young Adults With Relapsed or Refractory Neuroblastoma (time frame: 21 days, from study day 1). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01601535, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2019.