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NCT01512758

A Study of Alisertib (MLN8237) in Adult East Asian Participants With Advanced Solid Tumors or Lymphomas

Completed Phase 1 Results posted Last updated 15 March 2019
What this trial tests

Phase 1 trial testing Alisertib in Advanced Solid Tumors in 36 participants. Completed in 8 October 2013.

Timeline
6 February 2012
Primary endpoint
8 October 2013
8 October 2013

Quick facts

Lead sponsorMillennium Pharmaceuticals, Inc.
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Allocationnon randomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment36
Start date6 February 2012
Primary completion8 October 2013
Estimated completion8 October 2013
Sites1 location across Singapore

Drugs / interventions tested

Conditions studied

Sponsor

Millennium Pharmaceuticals, Inc. — full company profile →

Who can join

18 and older, any sex, with Advanced Solid Tumors or Lymphomas. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) Primary · Treatment Cycle 1

MTD was defined as highest dose at which \<2 participants experienced a dose-limiting toxicity (DLT). DLT was defined as any of the following events considered possibly related to therapy with alisertib by the investigator: 1. Grade 4 neutropenia (absolute neutrophil count \<500 cells/mm\^3) for \>7 days; 2. Grade 4 neutropenia with fever (oral or ear temperature ≥38.5°C); 3. Grade 4 thrombocytopenia (platelets \<25,000/mm\^3) for \>7 days; 4. Platelet count \<10,000 cells/mm\^3; 5. ≥Grade 3 thrombocytopenia with clinically significant bleeding; 6. Delay in initiation of subsequent cycle by \>

GroupValue95% CI
Alisertib 30 mg or 40 mg30
Number of Participants With Adverse Events and Serious Adverse Events Primary · First dose to 30 days past last dose (Up to 12.1 Months)

An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A Serious Adverse Event (SAE) A serious is any experience that suggests a significant hazard, contraindication, side effect or precaution that: results in death, is life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically significant.

AE
GroupValue95% CI
Alisertib 30 mg30
Alisertib 40 mg6
SAE
GroupValue95% CI
Alisertib 30 mg15
Alisertib 40 mg4
Number of Participants With Abnormal Clinical Laboratory Values Reported as Adverse Events Primary · First dose to 30 days past last dose (Up to 12.1 Months)

Laboratory AEs in the following system organ classes (SOCs) are reported: blood and lymphatic system disorders, investigations, and metabolism and nutrition disorders. An abnormal laboratory value was assessed as an AE if that value lead to discontinuation or delay in treatment, dose modification, therapeutic intervention, or was considered by the investigator to be a clinically significant change from baseline. A treatment¬-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.

Neutropenia
GroupValue95% CI
Alisertib 30 mg19
Alisertib 40 mg5
Anaemia
GroupValue95% CI
Alisertib 30 mg9
Alisertib 40 mg4
Thrombocytopenia
GroupValue95% CI
Alisertib 30 mg6
Alisertib 40 mg1
Febrile neutropenia
GroupValue95% CI
Alisertib 30 mg4
Alisertib 40 mg1
Leukopenia
GroupValue95% CI
Alisertib 30 mg2
Alisertib 40 mg2
White blood cell count decreased
GroupValue95% CI
Alisertib 30 mg7
Alisertib 40 mg0
Aspartate aminotransferase increased
GroupValue95% CI
Alisertib 30 mg6
Alisertib 40 mg0
Neutrophil count decreased
GroupValue95% CI
Alisertib 30 mg4
Alisertib 40 mg0
Number of Participants With Clinically Significant Changes in Vital Signs Reported as Adverse Events Primary · First dose to 30 days past last dose (Up to 12.1 Months)

Vital signs (blood pressure, pulse rate, and oral temperature) measurements were collected throughout the study.

Hypertension
GroupValue95% CI
Alisertib 30 mg1
Alisertib 40 mg0
Hypotension
GroupValue95% CI
Alisertib 30 mg1
Alisertib 40 mg0
Bradycardia
GroupValue95% CI
Alisertib 30 mg1
Alisertib 40 mg0
Pyrexia
GroupValue95% CI
Alisertib 30 mg8
Alisertib 40 mg1
Cmax: Maximum Observed Concentration for Alisertib Primary · Cycle 1 Days 1 and 7 predose and at multiple time points (up to 12 hours) postdose
Day 1
GroupValue95% CI
Alisertib 30 mg1442.5± 534.80
Alisertib 40 mg1871.7± 429.62
Day 7
GroupValue95% CI
Alisertib 30 mg3000.0± 1329.38
Alisertib 40 mg3686.7± 885.45
Tmax: Time to First Occurrence of Cmax for Alisertib Primary · Cycle 1 Days 1 and 7 predose and at multiple time points (up to 12 hours) postdose
Day 1
GroupValue95% CI
Alisertib 30 mg3.02 – 8
Alisertib 40 mg2.02 – 3
Day 7
GroupValue95% CI
Alisertib 30 mg2.91 – 6
Alisertib 40 mg2.01 – 3
AUCτ: Area Under the Concentration-Time Curve From Time 0 to End of Dosing Interval (τ) for Alisertib Primary · Cycle 1 Days 1 and 7 predose and at multiple time points (up to 12 hours) postdose
Day 1
GroupValue95% CI
Alisertib 30 mg9549.0± 4119.30
Alisertib 40 mg11811.7± 2845.76
Day 7
GroupValue95% CI
Alisertib 30 mg24377.9± 13261.61
Alisertib 40 mg30683.3± 9575.68
Dose Normalized AUCτ: Area Under the Concentration-Time Curve From Time 0 to Time t for Alisertib Primary · Cycle 1 Day 7 predose and at multiple time points (up to 12 hours) postdose

Dose normalized AUCτ was obtained using AUCτ divided by alisertib dose in milligrams.

GroupValue95% CI
Alisertib 30 mg812.9± 441.90
Alisertib 40 mg766.8± 238.88
T1/2: Terminal Half-Life for Alisertib Primary · Cycle 1 Day 7 predose and at multiple time points (up to 12 hours) postdose
GroupValue95% CI
Alisertib 30 mg16.750± 8.1710
Alisertib 40 mg14.795± 4.5715
Rac: Accumulation Ratio for Alisertib Primary · Cycle 1 Day 7 predose and at multiple time points (up to 12 hours) postdose
GroupValue95% CI
Alisertib 30 mg2.830± 1.2955
Alisertib 40 mg2.690± 1.0638
PTR: Peak Trough Ratio During a Dosing Interval, at Steady State for Alisertib Primary · Cycle 1 Day 7 predose and at multiple time points (up to 12 hours) postdose
GroupValue95% CI
Alisertib 30 mg2.254± 0.6458
Alisertib 40 mg2.207± 0.3946
CLss/F: Apparent Clearance After Extravascular Administration, at Steady State, Calculated Using AUCτ for Alisertib Primary · Cycle 1 Day 7 predose and at multiple time points (up to 12 hours) postdose
GroupValue95% CI
Alisertib 30 mg2.9357± 1.37091
Alisertib 40 mg2.8083± 1.20259

Adverse events — posted to ClinicalTrials.gov

Time frame: First dose to 30 days past last dose (Up to 12.1 Months). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Alisertib 30 mg
Serious: 15/30 (50%)
Deaths:
Alisertib 40 mg
Serious: 4/6 (67%)
Deaths:

Serious adverse events (25 terms)

ReactionSystemAlisertib 30 mgAlisertib 40 mg
Febrile neutropeniaBlood and lymphatic system disorders
StomatitisGastrointestinal disorders
NeutropeniaBlood and lymphatic system disorders
DiarrhoeaGastrointestinal disorders
AnaemiaBlood and lymphatic system disorders
LeukopeniaBlood and lymphatic system disorders
Upper gastrointestinal haemorrhageGastrointestinal disorders
Small intestinal obstructionGastrointestinal disorders
AscitesGastrointestinal disorders
BacteraemiaInfections and infestations
SepsisInfections and infestations
Subcutaneous abscessInfections and infestations
Urinary tract infectionInfections and infestations
Platelet count decreasedInvestigations
Neutrophil count decreasedInvestigations
Pain in extremityMusculoskeletal and connective tissue disorders
Lower extremity massMusculoskeletal and connective tissue disorders
Axillary massMusculoskeletal and connective tissue disorders
CholangiocarcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer painNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Pneumonia aspirationRespiratory, thoracic and mediastinal disorders
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
PyrexiaGeneral disorders
HypokalaemiaMetabolism and nutrition disorders
HaematocheziaGastrointestinal disorders
Other adverse events (56 terms — click to expand)

ReactionSystemAlisertib 30 mgAlisertib 40 mg
NeutropeniaBlood and lymphatic system disorders
DiarrhoeaGastrointestinal disorders
StomatitisGastrointestinal disorders
AlopeciaSkin and subcutaneous tissue disorders
FatigueGeneral disorders
AnaemiaBlood and lymphatic system disorders
Decreased appetiteMetabolism and nutrition disorders
Abdominal pain upperGastrointestinal disorders
PruritusSkin and subcutaneous tissue disorders
PyrexiaGeneral disorders
White blood cell count decreasedInvestigations
Abdominal painGastrointestinal disorders
NauseaGastrointestinal disorders
ThrombocytopeniaBlood and lymphatic system disorders
Aspartate aminotransferase increasedInvestigations
VomitingGastrointestinal disorders
AstheniaGeneral disorders
Alanine aminotransferase increasedInvestigations
Neutrophil count decreasedInvestigations
HypokalaemiaMetabolism and nutrition disorders
SomnolenceNervous system disorders
InsomniaPsychiatric disorders
ConstipationGastrointestinal disorders
Palmar-plantar erythrodysaesthesia syndromeSkin and subcutaneous tissue disorders
Rash maculo-papularSkin and subcutaneous tissue disorders
Oedema peripheralGeneral disorders
Platelet count decreasedInvestigations
LethargyNervous system disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
Back painMusculoskeletal and connective tissue disorders
Upper respiratory tract infectionInfections and infestations
Oral painGastrointestinal disorders
Mouth ulcerationGastrointestinal disorders
Abdominal discomfortGastrointestinal disorders
HaematocheziaGastrointestinal disorders
LeukopeniaBlood and lymphatic system disorders
Skin hyperpigmentationSkin and subcutaneous tissue disorders
Pigmentation disorderSkin and subcutaneous tissue disorders
Blood bilirubin increasedInvestigations

Most-reported serious reactions: Febrile neutropenia, Stomatitis, Neutropenia, Diarrhoea, Anaemia, Leukopenia, Upper gastrointestinal haemorrhage, Small intestinal obstruction.

Data from ClinicalTrials.gov NCT01512758 adverse events section.

Sponsor's own description

The purpose of this study was to determine the safety profile, maximum tolerated dose (MTD), recommended Phase 2 dose (RP2D), and to characterize the pharmacokinetic (PK) profile of alisertib twice daily (BID) dosing for 7 days in East Asian participants with advanced solid tumors or lymphomas. The secondary objective was to describe any antitumor activity that may have been observed with alisertib treatment.

Publications & conference data

5 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Aurora A kinase (AURKA) in normal and pathological cell division.
    Nikonova AS, Astsaturov I, Serebriiskii IG, Dunbrack RL, et al · · 2013 · cited 368× · PMID 22864622 · DOI 10.1007/s00018-012-1073-7
  2. Aurora kinase A in gastrointestinal cancers: time to target.
    Katsha A, Belkhiri A, Goff L, El-Rifai W. · · 2015 · cited 74× · PMID 25987188 · DOI 10.1186/s12943-015-0375-4
  3. Global population pharmacokinetics of the investigational Aurora A kinase inhibitor alisertib in cancer patients: rationale for lower dosage in Asia.
    Zhou X, Mould DR, Takubo T, Sheldon-Waniga E, et al · · 2018 · cited 17× · PMID 28891222 · DOI 10.1111/bcp.13430
  4. Aurora Kinases as Therapeutic Targets in Head and Neck Cancer.
    Nguyen TT, Silva FN, Golemis EA. · · 2022 · cited 8× · PMID 36165728 · DOI 10.1097/ppo.0000000000000614
  5. Knowledge mapping of AURKA in Oncology:An advanced Bibliometric analysis (1998-2023).
    Zhou Q, Tao C, Yuan J, Pan F, et al · · 2024 · cited 1× · PMID 38912486 · DOI 10.1016/j.heliyon.2024.e31945

Verify or expand the search:

Other trials of Alisertib

Trials testing the same drug.

Other recruiting trials for Advanced Solid Tumors

Currently open trials in the same condition.

Other Millennium Pharmaceuticals, Inc. trials

Trials by the same sponsor.

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing