MLN1117 in Combination With Docetaxel, Paclitaxel, and Other Investigational Anticancer Agents to Treat Participants With Gastric and Gastroesophageal Adenocarcinoma
TerminatedPhase 1Results postedLast 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.
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 1Primary· 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
Group
Value
95% CI
MLN1117 300 mg + Alisertib
0
MLN1117 600 mg + Alisertib
1
MLN1117 300 mg + Paclitaxel
0
MLN1117 600 mg + Paclitaxel
0
MLN1117 300 mg + TAK-659
1
MLN1117 200 mg + Docetaxel
0
MLN1117 300 mg + Docetaxel
1
Number of Participants With at Least 1 Treatment-Emergent Adverse Event (TEAE) in Part 1Primary· 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
Group
Value
95% CI
MLN1117 300 mg + Alisertib
4
MLN1117 600 mg + Alisertib
6
MLN1117 300 mg + Paclitaxel
3
MLN1117 600 mg + Paclitaxel
6
MLN1117 300 mg + TAK-659
7
MLN1117 200 mg + Docetaxel
2
MLN1117 300 mg + Docetaxel
4
Number of Participants With at Least 1 ≥ Grade 3 TEAE in Part 1Primary· 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;
Group
Value
95% CI
MLN1117 300 mg + Alisertib
4
MLN1117 600 mg + Alisertib
4
MLN1117 300 mg + Paclitaxel
2
MLN1117 600 mg + Paclitaxel
2
MLN1117 300 mg + TAK-659
6
MLN1117 200 mg + Docetaxel
2
MLN1117 300 mg + Docetaxel
4
Number of Participants With at Least 1 Treatment-Emergent Serious Adverse Event (SAE) in Part 1Primary· 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
Group
Value
95% CI
MLN1117 300 mg + Alisertib
2
MLN1117 600 mg + Alisertib
3
MLN1117 300 mg + Paclitaxel
1
MLN1117 600 mg + Paclitaxel
2
MLN1117 300 mg + TAK-659
5
MLN1117 200 mg + Docetaxel
2
MLN1117 300 mg + Docetaxel
4
Number of Participants With at Least 1 Dose Modification Due to AE in Part 1Primary· 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
Group
Value
95% CI
MLN1117 300 mg + Alisertib
0
MLN1117 600 mg + Alisertib
1
MLN1117 300 mg + Paclitaxel
1
MLN1117 600 mg + Paclitaxel
0
MLN1117 300 mg + TAK-659
4
MLN1117 200 mg + Docetaxel
0
MLN1117 300 mg + Docetaxel
1
Number of Participants With at Least 1 TEAE and Serious TEAE in Part 1 and 2Secondary· 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
Group
Value
95% CI
MLN1117 300 mg + Alisertib
4
MLN1117 600 mg + Alisertib
6
MLN1117 300 mg + Paclitaxel
3
MLN1117 600 mg + Paclitaxel
6
MLN1117 300 mg + TAK-659
7
MLN1117 200 mg + Docetaxel
2
MLN1117 300 mg + Docetaxel
4
SAE
Group
Value
95% CI
MLN1117 300 mg + Alisertib
2
MLN1117 600 mg + Alisertib
3
MLN1117 300 mg + Paclitaxel
1
MLN1117 600 mg + Paclitaxel
2
MLN1117 300 mg + TAK-659
5
MLN1117 200 mg + Docetaxel
2
MLN1117 300 mg + Docetaxel
4
Number of Participants With Dose Delays, Dose Reductions, and Dose Interruptions Due To AE in Part 1 and 2Secondary· 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
Group
Value
95% CI
MLN1117 300 mg + Alisertib
0
MLN1117 600 mg + Alisertib
0
MLN1117 300 mg + Paclitaxel
0
MLN1117 600 mg + Paclitaxel
0
MLN1117 300 mg + TAK-659
1
MLN1117 200 mg + Docetaxel
0
MLN1117 300 mg + Docetaxel
0
Dose reduction due to AE
Group
Value
95% CI
MLN1117 300 mg + Alisertib
0
MLN1117 600 mg + Alisertib
1
MLN1117 300 mg + Paclitaxel
1
MLN1117 600 mg + Paclitaxel
0
MLN1117 300 mg + TAK-659
4
MLN1117 200 mg + Docetaxel
0
MLN1117 300 mg + Docetaxel
1
Dose interruption due to AE
Group
Value
95% CI
MLN1117 300 mg + Alisertib
0
MLN1117 600 mg + Alisertib
0
MLN1117 300 mg + Paclitaxel
1
MLN1117 600 mg + Paclitaxel
0
MLN1117 300 mg + TAK-659
0
MLN1117 200 mg + Docetaxel
0
MLN1117 300 mg + Docetaxel
0
Plasma Concentration of MLN1117-1003Secondary· 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
Group
Value
95% CI
MLN1117 300 mg + Alisertib
NA
± NA
MLN1117 600 mg + Alisertib
NA
± NA
MLN1117 300 mg + Paclitaxel
NA
± NA
MLN1117 600 mg + Paclitaxel
NA
± NA
MLN1117 300 mg + TAK-659
0.00
± 0.000
MLN1117 200 mg + Docetaxel
NA
± NA
MLN1117 300 mg + Docetaxel
NA
± NA
Day 1: 0.5 Hour Postdose
Group
Value
95% CI
MLN1117 300 mg + Alisertib
NA
± NA
MLN1117 600 mg + Alisertib
NA
± NA
MLN1117 300 mg + Paclitaxel
NA
± NA
MLN1117 600 mg + Paclitaxel
NA
± NA
MLN1117 300 mg + TAK-659
675.04
± 816.641
MLN1117 200 mg + Docetaxel
NA
± NA
MLN1117 300 mg + Docetaxel
NA
± NA
Day 1: 1 Hour Postdose
Group
Value
95% CI
MLN1117 300 mg + Alisertib
NA
± NA
MLN1117 600 mg + Alisertib
NA
± NA
MLN1117 300 mg + Paclitaxel
NA
± NA
MLN1117 600 mg + Paclitaxel
NA
± NA
MLN1117 300 mg + TAK-659
2171.00
± 1840.041
MLN1117 200 mg + Docetaxel
NA
± NA
MLN1117 300 mg + Docetaxel
NA
± NA
Day 1: 2 Hours Postdose
Group
Value
95% CI
MLN1117 300 mg + Alisertib
NA
± NA
MLN1117 600 mg + Alisertib
NA
± NA
MLN1117 300 mg + Paclitaxel
NA
± NA
MLN1117 600 mg + Paclitaxel
NA
± NA
MLN1117 300 mg + TAK-659
3054.14
± 1811.084
MLN1117 200 mg + Docetaxel
NA
± NA
MLN1117 300 mg + Docetaxel
NA
± NA
Day 1: 3 Hours Postdose
Group
Value
95% CI
MLN1117 300 mg + Alisertib
NA
± NA
MLN1117 600 mg + Alisertib
NA
± NA
MLN1117 300 mg + Paclitaxel
NA
± NA
MLN1117 600 mg + Paclitaxel
NA
± NA
MLN1117 300 mg + TAK-659
3315.29
± 1521.130
MLN1117 200 mg + Docetaxel
NA
± NA
MLN1117 300 mg + Docetaxel
NA
± NA
Day 1: 4 Hours Postdose
Group
Value
95% CI
MLN1117 300 mg + Alisertib
NA
± NA
MLN1117 600 mg + Alisertib
NA
± NA
MLN1117 300 mg + Paclitaxel
NA
± NA
MLN1117 600 mg + Paclitaxel
NA
± NA
MLN1117 300 mg + TAK-659
3164.71
± 1522.096
MLN1117 200 mg + Docetaxel
NA
± NA
MLN1117 300 mg + Docetaxel
NA
± NA
Day 1: 6 Hours Postdose
Group
Value
95% CI
MLN1117 300 mg + Alisertib
NA
± NA
MLN1117 600 mg + Alisertib
NA
± NA
MLN1117 300 mg + Paclitaxel
NA
± NA
MLN1117 600 mg + Paclitaxel
NA
± NA
MLN1117 300 mg + TAK-659
2726.71
± 1259.976
MLN1117 200 mg + Docetaxel
NA
± NA
MLN1117 300 mg + Docetaxel
NA
± NA
Day 1: 8 Hours Postdose
Group
Value
95% CI
MLN1117 300 mg + Alisertib
NA
± NA
MLN1117 600 mg + Alisertib
NA
± NA
MLN1117 300 mg + Paclitaxel
NA
± NA
MLN1117 600 mg + Paclitaxel
NA
± NA
MLN1117 300 mg + TAK-659
2466.29
± 1112.350
MLN1117 200 mg + Docetaxel
NA
± NA
MLN1117 300 mg + Docetaxel
NA
± 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)
Reaction
System
MLN1117 300 mg + Alisertib
MLN1117 600 mg + Alisertib
MLN1117 300 mg + Paclitaxel
MLN1117 600 mg + Paclitaxel
MLN1117 300 mg + TAK-659
MLN1117 200 mg + Docetaxel
MLN1117 300 mg + Docetaxel
Sepsis
Infections and infestations
—
—
—
—
—
—
—
Febrile neutropenia
Blood and lymphatic system disorders
—
—
—
—
—
—
—
Abdominal pain
Gastrointestinal disorders
—
—
—
—
—
—
—
Impaired gastric emptying
Gastrointestinal disorders
—
—
—
—
—
—
—
Ascites
Gastrointestinal disorders
—
—
—
—
—
—
—
Oesophagitis
Gastrointestinal disorders
—
—
—
—
—
—
—
Rectal haemorrhage
Gastrointestinal disorders
—
—
—
—
—
—
—
Small intestinal obstruction
Gastrointestinal disorders
—
—
—
—
—
—
—
Upper gastrointestinal haemorrhage
Gastrointestinal disorders
—
—
—
—
—
—
—
Vomiting
Gastrointestinal disorders
—
—
—
—
—
—
—
Gastroenteritis
Infections and infestations
—
—
—
—
—
—
—
Lung infection
Infections and infestations
—
—
—
—
—
—
—
Osteomyelitis
Infections and infestations
—
—
—
—
—
—
—
Pelvic infection
Infections and infestations
—
—
—
—
—
—
—
Pneumonia
Infections and infestations
—
—
—
—
—
—
—
Haemorrhagic anaemia
Blood and lymphatic system disorders
—
—
—
—
—
—
—
Neutropenia
Blood and lymphatic system disorders
—
—
—
—
—
—
—
Ovarian cancer metastatic
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
—
—
—
—
—
—
—
Lymphangiosis carcinomatosa
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
—
—
—
—
—
—
—
Malignant neoplasm of ampulla of Vater
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
—
—
—
—
—
—
—
Neuroendocrine carcinoma metastatic
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
—
—
—
—
—
—
—
Non-small cell lung cancer metastatic
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
—
—
—
—
—
—
—
Dehydration
Metabolism and nutrition disorders
—
—
—
—
—
—
—
Hypokalaemia
Metabolism and nutrition disorders
—
—
—
—
—
—
—
Pyrexia
General disorders
—
—
—
—
—
—
—
Other adverse events (160 terms — click to expand)
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.
NCT02724020 — MLN0128 and MLN0128 + MLN1117 Compared With Everolimus in the Treatment of Adults With Advanced or Metastatic Clear-Cell
· Phase 2
· completed
NCT02725268 — A Study of Sapanisertib, Combination of Sapanisertib With MLN1117, Paclitaxel and Combination of Sapanisertib With Pacli
· Phase 2
· completed
Other Millennium Pharmaceuticals, Inc. trials
Trials by the same sponsor.
NCT03888534 — Intravenous Ixazomib in Pediatric Participants With Relapsed or Refractory Acute Lymphoblastic Leukemia (ALL) or Lymphob
· Phase 1
· withdrawn
NCT04056468 — A Study to Evaluate Pharmacokinetics (PK) and Safety of Oral Mobocertinib in Participants With Moderate or Severe Hepati
· Phase 1
· completed
NCT04454918 — Study to Assess Absolute Bioavailability (ABA) of TAK-906 and to Characterize Mass Balance, Pharmacokinetics (PK), Metab
· Phase 1
· completed
NCT04056455 — A Study of Mobocertinib Capsules in People With Severe Kidney Problems and People With Healthy Kidneys
· Phase 1
· completed
NCT04091438 — A Study of a Single Intravenous Infusion Dose of TAK-925 in Participants With Idiopathic Hypersomnia
· Phase 1
· completed
Drug + disease cross-links: matched in real time against Drug Landscape's normalised drug + company + condition tables
Sponsor: as reported to ClinicalTrials.gov by Millennium Pharmaceuticals, Inc.
Last refreshed: 20 September 2019
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.