Last reviewed · How we verify

NCT02551055

MLN1117 in Combination With Docetaxel, Paclitaxel, and Other Investigational Anticancer Agents to Treat Participants With Gastric and Gastroesophageal Adenocarcinoma

Terminated Phase 1 Results posted Last updated 20 September 2019
What this trial tests

Phase 1 trial testing MLN1117 in Advanced and Metastatic Gastric or Gastroesophageal Adenocarcinoma in 32 participants. Terminated before completion.

Timeline
15 October 2015
Primary endpoint
17 February 2017
17 February 2017

Quick facts

Lead sponsorMillennium Pharmaceuticals, Inc.
PhasePhase 1
StatusTerminated
Study typeINTERVENTIONAL
Allocationnon randomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment32
Start date15 October 2015
Primary completion17 February 2017
Estimated completion17 February 2017
Sites6 locations across United States, Spain

Drugs / interventions tested

Conditions studied

Sponsor

Millennium Pharmaceuticals, Inc. — full company profile →

Who can join

18 and older, any sex, with Advanced and Metastatic Gastric or Gastroesophageal Adenocarcinoma. 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.

Number of Participants Who Experienced Cycle 1 Dose Limiting Toxicity (DLT) in Part 1 Primary · Up to Cycle 1 (28 days for MLN1117+TAK-659, MLN1117+Alisertib, MLN1117+Paclitaxel or 21 days for MLN1117+Docetaxel)

Toxicity according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.0. DLT defined as any of following considered related to any of treatment by investigator: Grade 4 neutropenia (absolute neutrophil count \<500 cells/mm\^3) for \>7 days; ≥ Grade 3 neutropenia with coincident fever or infection; Grade 4 thrombocytopenia for \>7 days; Grade 3 thrombocytopenia with clinically significant bleeding; Platelet count \<10,000/mm\^3 at any time; Delay in initiation of subsequent therapy cycle by \>7 days due to treatment-related toxicity; ≥Grade 3 nonh

GroupValue95% CI
MLN1117 300 mg + Alisertib0
MLN1117 600 mg + Alisertib1
MLN1117 300 mg + Paclitaxel0
MLN1117 600 mg + Paclitaxel0
MLN1117 300 mg + TAK-6591
MLN1117 200 mg + Docetaxel0
MLN1117 300 mg + Docetaxel1
Number of Participants With at Least 1 Treatment-Emergent Adverse Event (TEAE) in Part 1 Primary · From first dose of study drug through 30 days after the last dose of study drug (approximately up to 366 days)

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

GroupValue95% CI
MLN1117 300 mg + Alisertib4
MLN1117 600 mg + Alisertib6
MLN1117 300 mg + Paclitaxel3
MLN1117 600 mg + Paclitaxel6
MLN1117 300 mg + TAK-6597
MLN1117 200 mg + Docetaxel2
MLN1117 300 mg + Docetaxel4
Number of Participants With at Least 1 ≥ Grade 3 TEAE in Part 1 Primary · From first dose of study drug through 30 days after the last dose of study drug (approximately up to 366 days)

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. TEAE is defined as an adverse event with an onset that occurs after receiving study drug. There are 5 grades of the CTCAE; "grade" refers to severity. Grade 5 is the most severe, grade 1 is the least severe. As per version 4.0 of the CTCAE, Grade 3 = AE with severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated;

GroupValue95% CI
MLN1117 300 mg + Alisertib4
MLN1117 600 mg + Alisertib4
MLN1117 300 mg + Paclitaxel2
MLN1117 600 mg + Paclitaxel2
MLN1117 300 mg + TAK-6596
MLN1117 200 mg + Docetaxel2
MLN1117 300 mg + Docetaxel4
Number of Participants With at Least 1 Treatment-Emergent Serious Adverse Event (SAE) in Part 1 Primary · From first dose of study drug through 30 days after the last dose of study drug (approximately up to 366 days)

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 SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect; or a medically important event. TEAE is defined as an adverse event with an onset that occurs aft

GroupValue95% CI
MLN1117 300 mg + Alisertib2
MLN1117 600 mg + Alisertib3
MLN1117 300 mg + Paclitaxel1
MLN1117 600 mg + Paclitaxel2
MLN1117 300 mg + TAK-6595
MLN1117 200 mg + Docetaxel2
MLN1117 300 mg + Docetaxel4
Number of Participants With at Least 1 Dose Modification Due to AE in Part 1 Primary · From first dose of study drug through 30 days after the last dose of study drug (approximately up to 366 days)

A decision regarding which study drug requires dose modification is dependent upon the toxicity, its onset, and time course. The causal relationship of each AE should will be assessed in relation to MLN1117 and to the combination agent in each cohort so that dose modifications can be made accordingly. Intrapatient dose reductions of MLN1117 are not permitted during Part 1 Cycle 1 unless the participant experiences a DLT attributed to MLN1117. Per dose modification guidelines, participants who have the study drug held because of treatment related or possibly related AEs may resume study drug tr

GroupValue95% CI
MLN1117 300 mg + Alisertib0
MLN1117 600 mg + Alisertib1
MLN1117 300 mg + Paclitaxel1
MLN1117 600 mg + Paclitaxel0
MLN1117 300 mg + TAK-6594
MLN1117 200 mg + Docetaxel0
MLN1117 300 mg + Docetaxel1
Number of Participants With at Least 1 TEAE and Serious TEAE in Part 1 and 2 Secondary · From first dose of study drug through 30 days after the last dose of study drug (approximately up to 366 days)

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 SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect; or a medically important event. TEAE is defined as an adverse event with an onset that occurs aft

AE
GroupValue95% CI
MLN1117 300 mg + Alisertib4
MLN1117 600 mg + Alisertib6
MLN1117 300 mg + Paclitaxel3
MLN1117 600 mg + Paclitaxel6
MLN1117 300 mg + TAK-6597
MLN1117 200 mg + Docetaxel2
MLN1117 300 mg + Docetaxel4
SAE
GroupValue95% CI
MLN1117 300 mg + Alisertib2
MLN1117 600 mg + Alisertib3
MLN1117 300 mg + Paclitaxel1
MLN1117 600 mg + Paclitaxel2
MLN1117 300 mg + TAK-6595
MLN1117 200 mg + Docetaxel2
MLN1117 300 mg + Docetaxel4
Number of Participants With Dose Delays, Dose Reductions, and Dose Interruptions Due To AE in Part 1 and 2 Secondary · From first dose of study drug through 30 days after the last dose of study drug (approximately up to 366 days)

Per dose modification guidelines, participants who have the study drug held because of treatment related or possibly related AEs may resume study drug treatment after resolution of the AE but may either maintain the same dose level or have doses of study drug reduced (dose reduction) by at least 1 dose level and if needed, by 2 dose levels.

Dose delay due to AE
GroupValue95% CI
MLN1117 300 mg + Alisertib0
MLN1117 600 mg + Alisertib0
MLN1117 300 mg + Paclitaxel0
MLN1117 600 mg + Paclitaxel0
MLN1117 300 mg + TAK-6591
MLN1117 200 mg + Docetaxel0
MLN1117 300 mg + Docetaxel0
Dose reduction due to AE
GroupValue95% CI
MLN1117 300 mg + Alisertib0
MLN1117 600 mg + Alisertib1
MLN1117 300 mg + Paclitaxel1
MLN1117 600 mg + Paclitaxel0
MLN1117 300 mg + TAK-6594
MLN1117 200 mg + Docetaxel0
MLN1117 300 mg + Docetaxel1
Dose interruption due to AE
GroupValue95% CI
MLN1117 300 mg + Alisertib0
MLN1117 600 mg + Alisertib0
MLN1117 300 mg + Paclitaxel1
MLN1117 600 mg + Paclitaxel0
MLN1117 300 mg + TAK-6590
MLN1117 200 mg + Docetaxel0
MLN1117 300 mg + Docetaxel0
Plasma Concentration of MLN1117-1003 Secondary · MLN1117 300 mg + Alisertib arms: Cycle 1 Day 3; MLN1117 300 mg + Paclitaxel arms and MLN1117 200 mg + Docetaxel arms: Cycle 1 Day 2; MLN1117 300 mg + TAK-659 arm: Cycle 1 Days 1 and 17
Day 1: Predose
GroupValue95% CI
MLN1117 300 mg + AlisertibNA± NA
MLN1117 600 mg + AlisertibNA± NA
MLN1117 300 mg + PaclitaxelNA± NA
MLN1117 600 mg + PaclitaxelNA± NA
MLN1117 300 mg + TAK-6590.00± 0.000
MLN1117 200 mg + DocetaxelNA± NA
MLN1117 300 mg + DocetaxelNA± NA
Day 1: 0.5 Hour Postdose
GroupValue95% CI
MLN1117 300 mg + AlisertibNA± NA
MLN1117 600 mg + AlisertibNA± NA
MLN1117 300 mg + PaclitaxelNA± NA
MLN1117 600 mg + PaclitaxelNA± NA
MLN1117 300 mg + TAK-659675.04± 816.641
MLN1117 200 mg + DocetaxelNA± NA
MLN1117 300 mg + DocetaxelNA± NA
Day 1: 1 Hour Postdose
GroupValue95% CI
MLN1117 300 mg + AlisertibNA± NA
MLN1117 600 mg + AlisertibNA± NA
MLN1117 300 mg + PaclitaxelNA± NA
MLN1117 600 mg + PaclitaxelNA± NA
MLN1117 300 mg + TAK-6592171.00± 1840.041
MLN1117 200 mg + DocetaxelNA± NA
MLN1117 300 mg + DocetaxelNA± NA
Day 1: 2 Hours Postdose
GroupValue95% CI
MLN1117 300 mg + AlisertibNA± NA
MLN1117 600 mg + AlisertibNA± NA
MLN1117 300 mg + PaclitaxelNA± NA
MLN1117 600 mg + PaclitaxelNA± NA
MLN1117 300 mg + TAK-6593054.14± 1811.084
MLN1117 200 mg + DocetaxelNA± NA
MLN1117 300 mg + DocetaxelNA± NA
Day 1: 3 Hours Postdose
GroupValue95% CI
MLN1117 300 mg + AlisertibNA± NA
MLN1117 600 mg + AlisertibNA± NA
MLN1117 300 mg + PaclitaxelNA± NA
MLN1117 600 mg + PaclitaxelNA± NA
MLN1117 300 mg + TAK-6593315.29± 1521.130
MLN1117 200 mg + DocetaxelNA± NA
MLN1117 300 mg + DocetaxelNA± NA
Day 1: 4 Hours Postdose
GroupValue95% CI
MLN1117 300 mg + AlisertibNA± NA
MLN1117 600 mg + AlisertibNA± NA
MLN1117 300 mg + PaclitaxelNA± NA
MLN1117 600 mg + PaclitaxelNA± NA
MLN1117 300 mg + TAK-6593164.71± 1522.096
MLN1117 200 mg + DocetaxelNA± NA
MLN1117 300 mg + DocetaxelNA± NA
Day 1: 6 Hours Postdose
GroupValue95% CI
MLN1117 300 mg + AlisertibNA± NA
MLN1117 600 mg + AlisertibNA± NA
MLN1117 300 mg + PaclitaxelNA± NA
MLN1117 600 mg + PaclitaxelNA± NA
MLN1117 300 mg + TAK-6592726.71± 1259.976
MLN1117 200 mg + DocetaxelNA± NA
MLN1117 300 mg + DocetaxelNA± NA
Day 1: 8 Hours Postdose
GroupValue95% CI
MLN1117 300 mg + AlisertibNA± NA
MLN1117 600 mg + AlisertibNA± NA
MLN1117 300 mg + PaclitaxelNA± NA
MLN1117 600 mg + PaclitaxelNA± NA
MLN1117 300 mg + TAK-6592466.29± 1112.350
MLN1117 200 mg + DocetaxelNA± NA
MLN1117 300 mg + DocetaxelNA± NA

Adverse events — posted to ClinicalTrials.gov

Time frame: From first dose of study drug through 30 days after the last dose of study drug. Related SAEs could be reported at any time after discontinuation.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

MLN1117 300 mg + Alisertib
Serious: 2/4 (50%)
Deaths: 0/4
MLN1117 600 mg + Alisertib
Serious: 3/6 (50%)
Deaths: 0/6
MLN1117 300 mg + Paclitaxel
Serious: 1/3 (33%)
Deaths: 1/3
MLN1117 600 mg + Paclitaxel
Serious: 2/6 (33%)
Deaths: 1/6
MLN1117 300 mg + TAK-659
Serious: 5/7 (71%)
Deaths: 1/7
MLN1117 200 mg + Docetaxel
Serious: 2/2 (100%)
Deaths: 1/2
MLN1117 300 mg + Docetaxel
Serious: 4/4 (100%)
Deaths: 2/4

Serious adverse events (33 terms)

ReactionSystemMLN1117 300 mg + AlisertibMLN1117 600 mg + AlisertibMLN1117 300 mg + PaclitaxelMLN1117 600 mg + PaclitaxelMLN1117 300 mg + TAK-659MLN1117 200 mg + DocetaxelMLN1117 300 mg + Docetaxel
SepsisInfections and infestations
Febrile neutropeniaBlood and lymphatic system disorders
Abdominal painGastrointestinal disorders
Impaired gastric emptyingGastrointestinal disorders
AscitesGastrointestinal disorders
OesophagitisGastrointestinal disorders
Rectal haemorrhageGastrointestinal disorders
Small intestinal obstructionGastrointestinal disorders
Upper gastrointestinal haemorrhageGastrointestinal disorders
VomitingGastrointestinal disorders
GastroenteritisInfections and infestations
Lung infectionInfections and infestations
OsteomyelitisInfections and infestations
Pelvic infectionInfections and infestations
PneumoniaInfections and infestations
Haemorrhagic anaemiaBlood and lymphatic system disorders
NeutropeniaBlood and lymphatic system disorders
Ovarian cancer metastaticNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Lymphangiosis carcinomatosaNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm of ampulla of VaterNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Neuroendocrine carcinoma metastaticNeoplasms benign, malignant and unspecified (incl cysts and polyps)
Non-small cell lung cancer metastaticNeoplasms benign, malignant and unspecified (incl cysts and polyps)
DehydrationMetabolism and nutrition disorders
HypokalaemiaMetabolism and nutrition disorders
PyrexiaGeneral disorders
Other adverse events (160 terms — click to expand)

ReactionSystemMLN1117 300 mg + AlisertibMLN1117 600 mg + AlisertibMLN1117 300 mg + PaclitaxelMLN1117 600 mg + PaclitaxelMLN1117 300 mg + TAK-659MLN1117 200 mg + DocetaxelMLN1117 300 mg + Docetaxel
NauseaGastrointestinal disorders
VomitingGastrointestinal disorders
Abdominal painGastrointestinal disorders
DehydrationMetabolism and nutrition disorders
Decreased appetiteMetabolism and nutrition disorders
NeutropeniaBlood and lymphatic system disorders
DiarrhoeaGastrointestinal disorders
FatigueGeneral disorders
Weight decreasedInvestigations
Back painMusculoskeletal and connective tissue disorders
InsomniaPsychiatric disorders
Periorbital oedemaEye disorders
ConstipationGastrointestinal disorders
DyspepsiaGastrointestinal disorders
Mouth ulcerationGastrointestinal disorders
HypokalaemiaMetabolism and nutrition disorders
HypomagnesaemiaMetabolism and nutrition disorders
HypophosphataemiaMetabolism and nutrition disorders
HypocalcaemiaMetabolism and nutrition disorders
ChillsGeneral disorders
Oedema peripheralGeneral disorders
PyrexiaGeneral disorders
MalaiseGeneral disorders
AnaemiaBlood and lymphatic system disorders
ThrombocytopeniaBlood and lymphatic system disorders
Night sweatsSkin and subcutaneous tissue disorders
AlopeciaSkin and subcutaneous tissue disorders
Dry skinSkin and subcutaneous tissue disorders
CoughRespiratory, thoracic and mediastinal disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
DizzinessNervous system disorders
HeadacheNervous system disorders
Peripheral sensory neuropathyNervous system disorders
Oral candidiasisInfections and infestations
Amylase increasedInvestigations
Lipase increasedInvestigations
MyalgiaMusculoskeletal and connective tissue disorders
StomatitisGastrointestinal disorders
Abdominal pain lowerGastrointestinal disorders
Abdominal pain upperGastrointestinal disorders

Most-reported serious reactions: Sepsis, Febrile neutropenia, Abdominal pain, Impaired gastric emptying, Ascites, Oesophagitis, Rectal haemorrhage, Small intestinal obstruction.

Data from ClinicalTrials.gov NCT02551055 adverse events section.

Sponsor's own description

The purpose of this study is to evaluate the maximum tolerated dose (MTD) or recommended Part 2 dose, safety and efficacy of MLN1117 (TAK-117) in combination with docetaxel, paclitaxel, investigational TAK-659 or investigational alisertib in adult participants with advanced and metastatic gastric or gastroesophageal adenocarcinoma. The study consists of a dose escalation phase (Part 1) and a dose expansion phase (Part 2).

Publications & conference data

No peer-reviewed publications indexed yet for this trial.

Verify or expand the search:

Other trials of MLN1117

Trials testing the same drug.

Other Millennium Pharmaceuticals, Inc. trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02551055.

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