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NCT00853307

MLN8237 for Treatment of Participants With Ovarian, Fallopian Tube, or Peritoneal Carcinoma

Completed Phase 2 Results posted Last updated 8 April 2022
What this trial tests

Phase 2 trial testing Alisertib in Ovarian Carcinoma in 31 participants. Completed in 27 January 2011.

Timeline
23 March 2009
Primary endpoint
23 November 2009
27 January 2011

Quick facts

Lead sponsorMillennium Pharmaceuticals, Inc.
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment31
Start date23 March 2009
Primary completion23 November 2009
Estimated completion27 January 2011
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

Millennium Pharmaceuticals, Inc. — full company profile →

Who can join

18 and older, female only, with Ovarian Carcinoma. 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.

Combined Best Overall Response Rate Based on Investigator Assessment Primary · Every 2 cycles up to 12 months until progressive disease (PD); Participants who discontinue study drug before PD: Follow-Up (FU)-every 12 weeks up to 12 months until PD/other cancer therapy; CA 125 Day 1 of cycle, End of Treatment and FU (Up to 22 Months)

Combined objective response rate is defined as the percentage of participants with Complete Response (CR) + Partial Response (PR) as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.1 or response by Cancer antigen (CA) 125 criteria. According to RECIST: CR is defined as disappearance of all target lesions and PR is defined as 30% decrease in the sum of the longest diameter of target lesions. CA 125 response criteria is defined as either: A 50% decrease from 2 initially elevated samples; the sample demonstrating the 50% decrease must hav

GroupValue95% CI
Alisertib 50 mg (Platinum-Refractory)0
Alisertib 50 mg (Platinum-Resistant)12
Progression Free Survival (PFS) Secondary · Every 2 cycles up to 12 months until PD; Participants who discontinue study drug before PD: FU - every 12 weeks up to 12 months until PD/other cancer therapy; CA 125 Day 1 of cycle, End of Treatment and FU (Up to 22 Months)

PFS is defined as the time in days from the date of first study drug administration to the date of first documented Progressive Disease (PD) or death. PD is defined as 20% increase in the sum of the longest diameter of target lesions. CA 125 progression for participants with normal CA 125 levels is defined as a CA 125 level \> 2 times the upper limit of normal and for participants with elevated values during the trial, is defined as a CA 125 level greater than 2 times the nadir value of CA 125. For a participant who has not progressed and has not died, PFS is censored at the last response asse

GroupValue95% CI
Alisertib 50 mg (Platinum-Refractory)36.523.0 – 120.0
Alisertib 50 mg (Platinum-Resistant)77.043.0 – 122.0
Clinical Benefit Rate Secondary · Every 2 cycles up to 12 months until PD; Participants who discontinue study drug before PD: FU - every 12 weeks up to 12 months until PD/other cancer therapy; CA 125 Day 1 of cycle, End of Treatment and FU (Up to 22 Months)

Clinical benefit rate is defined as the percentage of participants with response and stable disease (SD), where in order for SD to qualify as having clinical benefit, there must be no progression of neoplastic disease for at least 4 treatment cycles.

GroupValue95% CI
Alisertib 50 mg (Platinum-Refractory)0
Alisertib 50 mg (Platinum-Resistant)32
Number of Participants With Treatment-Emergent Adverse Events and Serious Adverse Events Secondary · First dose to 30 days past last dose (Up to 18.9 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. A

AE
GroupValue95% CI
Alisertib 50 mg (Platinum-Refractory)6
Alisertib 50 mg (Platinum-Resistant)24
SAE
GroupValue95% CI
Alisertib 50 mg (Platinum-Refractory)4
Alisertib 50 mg (Platinum-Resistant)7
Number of Participants With Abnormal Vital Signs Reported as Treatment-Emergent Adverse Events Secondary · Baseline, Cycle 1 Days 8 and 15, then Day 1 of every cycle (21 days), End of Treatment, End of Study/FU every 12 weeks for up to 12 months (Up to 22 Months)

Vital signs included blood pressure, pulse rate, and oral temperature collected throughout the study. . A treatment-emergent adverse event is defined as an adverse event with an onset that occurs after receiving study drug.

Pyrexia
GroupValue95% CI
Alisertib 50 mg (Platinum-Refractory)2
Alisertib 50 mg (Platinum-Resistant)6
Dyspnoea
GroupValue95% CI
Alisertib 50 mg (Platinum-Refractory)0
Alisertib 50 mg (Platinum-Resistant)4
Weight decreased
GroupValue95% CI
Alisertib 50 mg (Platinum-Refractory)0
Alisertib 50 mg (Platinum-Resistant)3
Tachycardia
GroupValue95% CI
Alisertib 50 mg (Platinum-Refractory)0
Alisertib 50 mg (Platinum-Resistant)2
Hypertension
GroupValue95% CI
Alisertib 50 mg (Platinum-Refractory)0
Alisertib 50 mg (Platinum-Resistant)2
Dyspnoea exertional
GroupValue95% CI
Alisertib 50 mg (Platinum-Refractory)0
Alisertib 50 mg (Platinum-Resistant)1
Bradycardia
GroupValue95% CI
Alisertib 50 mg (Platinum-Refractory)0
Alisertib 50 mg (Platinum-Resistant)1
Shock
GroupValue95% CI
Alisertib 50 mg (Platinum-Refractory)1
Alisertib 50 mg (Platinum-Resistant)0
Number of Participants With Abnormal Laboratory Values Reported as Treatment-Emergent Adverse Events Secondary · Baseline, Cycle 1 Days 8 and 15, then Every cycle Days 1, 8 and 15 to End of Treatment Up to 18.0 Months

Laboratory tests included Hematology and Chemistry. Abnormal laboratory value were assessed as an AE if the value leads to discontinuation or delay in treatment, dose modification, therapeutic intervention, or is 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 50 mg (Platinum-Refractory)3
Alisertib 50 mg (Platinum-Resistant)17
Anaemia
GroupValue95% CI
Alisertib 50 mg (Platinum-Refractory)2
Alisertib 50 mg (Platinum-Resistant)14
Leukopenia
GroupValue95% CI
Alisertib 50 mg (Platinum-Refractory)1
Alisertib 50 mg (Platinum-Resistant)11
Thrombocytopenia
GroupValue95% CI
Alisertib 50 mg (Platinum-Refractory)1
Alisertib 50 mg (Platinum-Resistant)8
Dehydration
GroupValue95% CI
Alisertib 50 mg (Platinum-Refractory)1
Alisertib 50 mg (Platinum-Resistant)7
Hypokalaemia
GroupValue95% CI
Alisertib 50 mg (Platinum-Refractory)2
Alisertib 50 mg (Platinum-Resistant)4
Alanine aminotransferase increased
GroupValue95% CI
Alisertib 50 mg (Platinum-Refractory)0
Alisertib 50 mg (Platinum-Resistant)6
Aspartate aminotransferase increased
GroupValue95% CI
Alisertib 50 mg (Platinum-Refractory)0
Alisertib 50 mg (Platinum-Resistant)6

Adverse events — posted to ClinicalTrials.gov

Time frame: First dose of study drug to 30 past last dose of study drug (Up to18.9 Months). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Alisertib 50 mg (Platinum-Refractory)
Serious: 4/6 (67%)
Deaths:
Alisertib 50 mg (Platinum-Resistant)
Serious: 7/25 (28%)
Deaths:

Serious adverse events (19 terms)

ReactionSystemAlisertib 50 mg (Platinum-…Alisertib 50 mg (Platinum-…
Febrile neutropeniaBlood and lymphatic system disorders
PyrexiaGeneral disorders
StomatitisGastrointestinal disorders
Abdominal painGastrointestinal disorders
Abdominal massGastrointestinal disorders
Small intestinal obstructionGastrointestinal disorders
Intestinal obstructionGastrointestinal disorders
VomitingGastrointestinal disorders
NeutropeniaBlood and lymphatic system disorders
AnaemiaBlood and lymphatic system disorders
LeukopeniaBlood and lymphatic system disorders
ThrombocytopeniaBlood and lymphatic system disorders
Clostridium colitisInfections and infestations
BacteraemiaInfections and infestations
HypokalaemiaMetabolism and nutrition disorders
DehydrationMetabolism and nutrition disorders
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
ShockVascular disorders
HypoaesthesiaNervous system disorders
Other adverse events (77 terms — click to expand)

ReactionSystemAlisertib 50 mg (Platinum-…Alisertib 50 mg (Platinum-…
NeutropeniaBlood and lymphatic system disorders
FatigueGeneral disorders
DiarrhoeaGastrointestinal disorders
AlopeciaSkin and subcutaneous tissue disorders
StomatitisGastrointestinal disorders
AnaemiaBlood and lymphatic system disorders
NauseaGastrointestinal disorders
LeukopeniaBlood and lymphatic system disorders
VomitingGastrointestinal disorders
Abdominal painGastrointestinal disorders
ThrombocytopeniaBlood and lymphatic system disorders
AnorexiaMetabolism and nutrition disorders
DehydrationMetabolism and nutrition disorders
Alanine aminotransferase increasedInvestigations
Aspartate aminotransferase increasedInvestigations
PyrexiaGeneral disorders
Dry skinSkin and subcutaneous tissue disorders
HeadacheNervous system disorders
ConstipationGastrointestinal disorders
PruritusSkin and subcutaneous tissue disorders
Rash pruriticSkin and subcutaneous tissue disorders
HyperglycaemiaMetabolism and nutrition disorders
HypokalaemiaMetabolism and nutrition disorders
HypomagnesaemiaMetabolism and nutrition disorders
SomnolenceNervous system disorders
Blood alkaline phosphatase increasedInvestigations
CoughRespiratory, thoracic and mediastinal disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Pharyngolaryngeal painRespiratory, thoracic and mediastinal disorders
AstheniaGeneral disorders
Oedema peripheralGeneral disorders
Weight decreasedInvestigations
Back painMusculoskeletal and connective tissue disorders
Urinary tract infectionInfections and infestations
AscitesGastrointestinal disorders
FlatulenceGastrointestinal disorders
Abdominal distensionGastrointestinal disorders
Abdominal pain upperGastrointestinal disorders
DysphagiaGastrointestinal disorders
Gingival bleedingGastrointestinal disorders

Most-reported serious reactions: Febrile neutropenia, Pyrexia, Stomatitis, Abdominal pain, Abdominal mass, Small intestinal obstruction, Intestinal obstruction, Vomiting.

Data from ClinicalTrials.gov NCT00853307 adverse events section.

Sponsor's own description

The purpose of this study is to evaluate the anti-tumour activity of alisertib (MLN8237) in the treatment of participants with platinum-refractory or platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal carcinomas.

Publications & conference data

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

  1. Mitotic chromosomal instability and cancer: mouse modelling of the human disease.
    Schvartzman JM, Sotillo R, Benezra R. · · 2010 · cited 349× · PMID 20094045 · DOI 10.1038/nrc2781
  2. The two sides of chromosomal instability: drivers and brakes in cancer.
    Hosea R, Hillary S, Naqvi S, Wu S, et al · · 2024 · cited 102× · PMID 38553459 · DOI 10.1038/s41392-024-01767-7
  3. 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
  4. Emerging roles of Aurora-A kinase in cancer therapy resistance.
    Zheng D, Li J, Yan H, Zhang G, et al · · 2023 · cited 71× · PMID 37521867 · DOI 10.1016/j.apsb.2023.03.013
  5. Therapeutic Inducers of Apoptosis in Ovarian Cancer.
    Binju M, Amaya-Padilla MA, Wan G, Gunosewoyo H, et al · · 2019 · cited 48× · PMID 31766284 · DOI 10.3390/cancers11111786
  6. Second-Generation Antimitotics in Cancer Clinical Trials.
    Novais P, Silva PMA, Amorim I, Bousbaa H. · · 2021 · cited 37× · PMID 34371703 · DOI 10.3390/pharmaceutics13071011
  7. A current review of targeted therapeutics for ovarian cancer.
    Campos SM, Ghosh S. · · 2010 · cited 28× · PMID 20069122 · DOI 10.1155/2010/149362
  8. 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

Verify or expand the search:

Other trials of Alisertib

Trials testing the same drug.

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Trials by the same sponsor.

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