Unspecified Childhood Solid Tumor, Excluding CNSPhase 1NCT02444884
MLN8237 to Treat Children With Relapsed/Refractory Solid Tumors
A Phase 1 study testing MLN8237 in people with Unspecified Childhood Solid Tumor, Excluding CNS and Neuroblastoma, run by Children's Oncology Group.
Trial summary
RATIONALE: MLN8237 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. PURPOSE: This phase I/II trial is studying the side effects and best dose of MLN8237 and to see how well it works in treating young patients with relapsed or refractory solid tumors Read more about this study
- Who is it for?
- Ages 12 months to 21 years
- Conditions the study is for
- Unspecified Childhood Solid Tumor, Excluding CNS, Neuroblastoma
- What is being tested?
- MLN8237
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 54 participants
- Where
- No sites listed yet
- Study dates
- Sep 2008to Dec 2011
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Diagnosis: Patients must have had histologic verification of malignancy at original diagnosis or relapse except in patients with intrinsic brain stem tumors, optic pathway gliomas, or patients with pineal tumors and elevations of CSF or serum tumor markers including alpha-fetaprotein or beta-HCG.
- Performance Level: Karnofsky >/= 50% for patients > 16 years of age and Lansky
- >/= 50 for patients </=16 years of age
- Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
- Adequate Bone Marrow Function Defined as:
- For patients with solid tumors:
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- Peripheral absolute neutrophil count (ANC) >/= 1000/microLiter
- Platelet count >/= 100,000/microLiter (transfusion independent, defined as not receiving platelet transfusions within a 7 day period prior to enrollment)
- Hemoglobin >/= 8.0 g/dL (may receive RBC transfusions)
- Creatinine clearance or radioisotope GFR >/= 70ml/min/1.73 m2
- Bilirubin (sum of conjugated + unconjugated) </= 1.5 x upper limit of normal (ULN) for age, and
- SGPT (ALT) </= 5.0 x ULN for age (≤ 225 U/L). For the purpose of this study, the ULN for SGPT is 45 U/L.
- Serum albumin >/= 2 g/dL.
Who cannot join
- Pregnant or breast-feeding women will not be entered on this study
- Growth factors that support platelet or white cell number or function must not have been administered within the 7 days prior to enrollment.
- Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for the prior 7 days are not eligible.
- Patients who are currently receiving another investigational drug are not eligible.
- Patients who are currently receiving other anticancer agents, digoxin, cyclosporine, tacrolimus or sirolimus, use of daily benzodiazepines are not eligible
- Patients who have an uncontrolled infection are not eligible.
About this study
Official title: A Phase I/II Study of MLN8237, an Oral Selective Small Molecule Inhibitor of Aurora A Kinase, in Children With Relapsed/Refractory Solid Tumors
RATIONALE: MLN8237 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
PURPOSE: This phase I/II trial is studying the side effects and best dose of MLN8237 and to see how well it works in treating young patients with relapsed or refractory solid tumors
Read the detailed description
1.1 Primary Aims 1.1.1 To estimate the maximum tolerated dose (MTD) and recommended Phase II dose of MLN8237 administered orally once daily for 7 days every 21 days to children with refractory solid tumors. 1.1.2 To estimate the maximum tolerated dose (MTD) and recommended Phase II dose of MLN8237 administered orally twice daily for 7 days every 21 days to children with refractory solid tumors. 1.1.3 To define and describe the toxicities of MLN8237 administered on this schedule.
1.1.4 To characterize the pharmacokinetics of MLN8237 in children with refractory cancer.
1.2 Secondary Aims 1.2.1 To preliminarily define the antitumor activity of MLN8237 within the confines of a Phase I study. 1.2.2 To obtain initial Phase II efficacy data on the anti-tumor activity of MLN8237 in children with relapsed-refractory neuroblastoma using the once daily dosing schedule. 1.2.3 To explore the relationship between polymorphic variations in the UDPglucuronyltransferase gene UGT1A1 and exposure to MLN8237.
1.2.4 To assess two common polymorphic variants in the Aurora A kinase gene (Phe31Ile and Val57Ile) thought to potentially influence tumorigenesis. 1.2.5 To preliminarily examine the relationsh
- Being tested
- MLN8237
- Medical subject headings
- Neuroblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MLN8237Drug
Also called Alisertib
| Study group | Role | What they receive |
|---|---|---|
| Stratum A1 | Experimental | Establish MTD in patients with solid tumors MLN8237 orally, once daily on Days 1-7 Receives: Drug: MLN8237 |
| Stratum A2 | Experimental | MTD determined in Stratum A1in patients with solid tumors MLN8237 orally, twice daily on Days 1-7 Receives: Drug: MLN8237 |
| Stratum B | Experimental | Expand MTD in patients with neuroblastoma MLN8237 orally, once daily on Days 1-7 Receives: Drug: MLN8237 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine maximum tolerated dose and RP2D administered once daily on Days 1-7
Measured: Up to 21 days (1st cycle) of protocol therapy
Determine maximum tolerated dose and RP2D administered po BID on Days 1-7
Measured: Up to 21 days (1st cycle) of protocol therapy
Adverse events as assessed by (CTCAE) version 4.0
DLT will be defined as possibly, probably or definitely attributable to MLN8237. The DLT observation period for the purposes of dose-escalation will be the first cycle of therapy
Measured: Every 21 days (each cycle) of protocol therapy for up to 35 cycles [up to 105 weeks]
PK Profile: MLN8237 concentrations in plasma samples
single-dose AUC, trough estimation, t½ of accumulation
Measured: 30 min after the first dose, and at 1,2, 3, 4, 6-8, 24 hours, Day 4 and 7 in Cycle 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 May 2015 (estimated)
- Study startSep 2008
- Primary completionDec 2011
- Study completionDec 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Unspecified Childhood Solid Tumor, Excluding CNSStudies of the same condition, open and under way.
- More trials run by Children's Oncology GroupThe sponsor's other registered studies.
- 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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 54 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Oncology Group
- Sponsor type
- Research network
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02444884
- Sponsor's protocol ID
- ADVL0812
- Status last verified
- Feb 2016
- First submitted
- 7 May 2015
- Last updated
- 9 Feb 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Zhou X, Mould DR, Yuan Y, Fox E, Greengard E, Faller DV, Venkatakrishnan K. Population Pharmacokinetics and Exposure-Safety Relationships of Alisertib in Children and Adolescents With Advanced Malignancies. J Clin Pharmacol. 2022 Feb;62(2):206-219. doi: 10.1002/jcph.1958. Epub 2022 Jan 15.
PubMed 34435684
Study at a glance
From the registry record, last updated by the sponsor on 9 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Study of MLN8237, an Oral Selective Small Molecule Inhibitor of Aurora A Kinase, in Children With Relapsed/Refractory Solid Tumors
- ClinicalTrials.gov ID
- NCT02444884
- Acronym / sponsor ID
- ADVL0812
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 54 participants (actual)
- Lead sponsor
- Children's Oncology GroupResearch network
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Sep 2008
- Primary completion
- Dec 2011 (actual)
- Study completion
- Dec 2011 (actual)
- First posted
- 15 May 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: MLN8237 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
PURPOSE: This phase I/II trial is studying the side effects and best dose of MLN8237 and to see how well it works in treating young patients with relapsed or refractory solid tumors
Detailed description
1.1 Primary Aims 1.1.1 To estimate the maximum tolerated dose (MTD) and recommended Phase II dose of MLN8237 administered orally once daily for 7 days every 21 days to children with refractory solid tumors. 1.1.2 To estimate the maximum tolerated dose (MTD) and recommended Phase II dose of MLN8237 administered orally twice daily for 7 days every 21 days to children with refractory solid tumors. 1.1.3 To define and describe the toxicities of MLN8237 administered on this schedule.
1.1.4 To characterize the pharmacokinetics of MLN8237 in children with refractory cancer.
1.2 Secondary Aims 1.2.1 To preliminarily define the antitumor activity of MLN8237 within the confines of a Phase I study. 1.2.2 To obtain initial Phase II efficacy data on the anti-tumor activity of MLN8237 in children with relapsed-refractory neuroblastoma using the once daily dosing schedule. 1.2.3 To explore the relationship between polymorphic variations in the UDPglucuronyltransferase gene UGT1A1 and exposure to MLN8237.
1.2.4 To assess two common polymorphic variants in the Aurora A kinase gene (Phe31Ile and Val57Ile) thought to potentially influence tumorigenesis. 1.2.5 To preliminarily examine the relationsh
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Stratum A1 | Experimental | Drug: MLN8237Establish MTD in patients with solid tumors MLN8237 orally, once daily on Days 1-7 |
| Stratum A2 | Experimental | Drug: MLN8237MTD determined in Stratum A1in patients with solid tumors MLN8237 orally, twice daily on Days 1-7 |
| Stratum B | Experimental | Drug: MLN8237Expand MTD in patients with neuroblastoma MLN8237 orally, once daily on Days 1-7 |
Who may qualify
- Ages
- 12 months to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (13 listed)
- Diagnosis: Patients must have had histologic verification of malignancy at original diagnosis or relapse except in patients with intrinsic brain stem tumors, optic pathway gliomas, or patients with pineal tumors and elevations of CSF or serum tumor markers including alpha-fetaprotein or beta-HCG.
- Performance Level: Karnofsky >/= 50% for patients > 16 years of age and Lansky
- >/= 50 for patients </=16 years of age
- Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
- Adequate Bone Marrow Function Defined as:
Key exclusion criteria (6 listed)
- Pregnant or breast-feeding women will not be entered on this study
- Growth factors that support platelet or white cell number or function must not have been administered within the 7 days prior to enrollment.
- Patients receiving corticosteroids who have not been on a stable or decreasing dose of corticosteroid for the prior 7 days are not eligible.
- Patients who are currently receiving another investigational drug are not eligible.
- Patients who are currently receiving other anticancer agents, digoxin, cyclosporine, tacrolimus or sirolimus, use of daily benzodiazepines are not eligible
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 |
|---|---|---|
| MLN8237Also: Alisertib | Drug | Stratum A1, Stratum A2, Stratum B |
Primary outcome
Determine maximum tolerated dose and RP2D administered once daily on Days 1-7
Time frame: Up to 21 days (1st cycle) of protocol therapy
Determine maximum tolerated dose and RP2D administered po BID on Days 1-7
Time frame: Up to 21 days (1st cycle) of protocol therapy
Adverse events as assessed by (CTCAE) version 4.0
Time frame: Every 21 days (each cycle) of protocol therapy for up to 35 cycles [up to 105 weeks]
DLT will be defined as possibly, probably or definitely attributable to MLN8237. The DLT observation period for the purposes of dose-escalation will be the first cycle of therapy
PK Profile: MLN8237 concentrations in plasma samples
Time frame: 30 min after the first dose, and at 1,2, 3, 4, 6-8, 24 hours, Day 4 and 7 in Cycle 1
single-dose AUC, trough estimation, t½ of accumulation
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Feb 2016.
- Derived from this study: PubMed 34435684Zhou X, Mould DR, Yuan Y, Fox E, Greengard E, Faller DV, Venkatakrishnan K. Population Pharmacokinetics and Exposure-Safety Relationships of Alisertib in Children and Adolescents With Advanced Malignancies. J Clin Pharmacol. 2022 Feb;62(2):206-219. doi: 10.1002/jcph.1958. Epub 2022 Jan 15.
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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing MLN8237 in people with Unspecified Childhood Solid Tumor, Excluding CNS and Neuroblastoma, run by Children's Oncology Group.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 6 exclusion criteria. 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 9 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.
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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Determine maximum tolerated dose and RP2D administered once daily on Days 1-7 (time frame: Up to 21 days (1st cycle) of protocol therapy). The study lists 4 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 NCT02444884, 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 9 Feb 2016.