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Trial record 59 of 59 for:    MLN8237

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02551055
Recruitment Status : Terminated (Business Decision; No Safety Or Efficacy Concerns.)
First Posted : September 16, 2015
Last Update Posted : August 17, 2017
Sponsor:
Information provided by (Responsible Party):
Takeda ( Millennium Pharmaceuticals, Inc. )

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Neoplasms, Advanced or Metastatic Drug: MLN1117 Drug: TAK-659 Drug: Alisertib Drug: Paclitaxel Drug: Docetaxel Phase 1

Detailed Description:

This study will look at the dose-limiting toxicity and response to treatment in participants who take MLN1117 in combination with TAK-659, paclitaxel or docetaxel or investigational TAK-659 or investigational alisertib.

The study will enroll approximately 60 participants in the dose escalation phase (Part 1) and 118 participants in the dose expansion phase (Part 2). Participants will be randomly assigned to 1 of the 4 treatment groups:

  • MLN1117 + TAK-659
  • MLN1117 + alisertib
  • MLN1117 + paclitaxel
  • MLN1117 + docetaxel

In Part 1, dose of MLN1117 will be increased step by step. All participants will be asked to take tablets of MLN1117 for 3 days on and 4 days off per week in 28-day treatment cycles or 21-day treatment cycles when given in combination with the other companion drugs.

This multi-centre trial will be conducted worldwide.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 32 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Umbrella Study to Evaluate MLN1117 in Combination With Taxanes (Docetaxel or Paclitaxel) and Other Investigational Anticancer Agents for the Treatment of Patients With Previously Treated Advanced and Metastatic Gastric and Gastroesophageal Adenocarcinoma
Actual Study Start Date : September 30, 2015
Actual Primary Completion Date : February 17, 2017
Actual Study Completion Date : February 17, 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: MLN1117 + TAK-659 (Cohort A)
MLN1117 300, 600 or 900 milligram (mg), tablets, orally, once daily for 3 days on (Days 1, 2, 3; 8, 9, 10; 15, 16, 17; 22, 23, and 24) and 4 days off per week and TAK-659 100 mg (as determined in study C34001 [NCT02000934]), tablets, orally, once daily, in 28-day treatment cycles until progressive disease or unacceptable toxicity.
Drug: MLN1117
MLN1117 Tablets
Other Name: TAK-117

Drug: TAK-659
TAK-659 Tablets

Experimental: MLN1117 + Alisertib (Cohort B)
MLN1117 300, 600 or 900 mg, tablets, orally, once daily for 3 days on (Days 1, 2, 3; 8, 9, 10; 15, 16, 17; 22, 23, and 24) and 4 days off per week and alisertib, 40 mg, tablets, orally, twice daily for 3 days on (Days 1, 2, 3; 8, 9, 10; 15,16, and 17) and 4 days off per week on Weeks 1-3, and 1 week off in 28-day treatment cycles until progressive disease or unacceptable toxicity.
Drug: MLN1117
MLN1117 Tablets
Other Name: TAK-117

Drug: Alisertib
Alisertib Tablets
Other Name: MLN8237

Experimental: MLN1117 + Paclitaxel (Cohort C)
MLN1117 300, 600, or 900 mg, tablets, orally, once daily for 3 days on (Days 2, 3, 4; 9, 10, 11; 16, 17, 18; 23, 24, and 25) and 4 days off per week and paclitaxel 80 milligram per square meter (mg/m^2), infusion, intravenously, once weekly on Days 1, 8, and 15, and 1 week off, in 28-day treatment cycles until progressive disease or unacceptable toxicity.
Drug: MLN1117
MLN1117 Tablets
Other Name: TAK-117

Drug: Paclitaxel
Paclitaxel intravenous infusion

Experimental: MLN1117 + Docetaxel (Cohort D)
MLN1117 300, 600, or 900 mg, orally, once daily for 3 days on (Days 2, 3, 4; 9, 10, 11; 16, 17, and 18) and 4 days off per week and docetaxel 75 mg/m^2, infusion, intravenously, on Day 1 once every 3 week in 21-day treatment cycles until progressive disease or unacceptable toxicity.
Drug: MLN1117
MLN1117 Tablets
Other Name: TAK-117

Drug: Docetaxel
Docetaxel intravenous infusion




Primary Outcome Measures :
  1. Part 1: Number of Participants With Dose-Limiting Toxicities (DLTs) [ Time Frame: From first dose through Day 28 (TAK-659, Alisertib, Paclitaxel groups) or Day 21 (Docetaxel group) ]
    Toxicity according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE),version 4.03. DLT defined as any of the following considered possibly related to therapy by investigator: Grade 4 neutropenia for > 7 days; ≥ Grade 3 neutropenia with fever/infection; Grade 4 thrombocytopenia for > 7 days; platelet count < 10,000 /mm^3; Grade 3 thrombocytopenia with clinically significant bleeding; ≥ Grade 3 nonhematologic toxicity except: Grade 3 arthralgia/myalgia, ≥ Grade 3 nausea/emesis, diarrhea controlled in 7 days by optimal therapy, Grade 3 fatigue, rash for ≤ 7days, Grade 2 fasting hyperglycemia for ≤ 14 days or Grade 3 fasting hyperglycemia for ≤ 24 hours with optimal treatment, other Grade 3 nonhematological toxicity controlled with appropriate treatment; delay in the initiation of the subsequent therapy cycle by ≥ 7 days; ≥ Grade 2 related nonhematologic toxicity.

  2. Part 1: Number of Participants With One or More Treatment Emergent Adverse Event (TEAE) [ Time Frame: From first dose up to 30 days after last dose ]
    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. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs after receiving study drug.

  3. Part 1: Number of Participants With One or More Grade 3 or Higher Treatment Emergent Adverse Event (TEAE) [ Time Frame: From first dose up to 30 days after last dose ]
    An 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. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. TEAE is defined as an adverse event with an onset that occurs after receiving study drug. As per Common Terminology Criteria for Adverse Events v4.0 (CTCAE), Grade 3 = AE with severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. Grade 4 = AE with life-threatening consequences; urgent intervention indicated and Grade 5 = Death related to AE.

  4. Part 1: Number of Participants With One or More Treatment Emergent Serious Adverse Event [ Time Frame: From first dose up to 30 days after last dose ]
    An 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. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A serious adverse event (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; or congenital anomaly; or a medically important event. TEAE is defined as an adverse event with an onset that occurs after receiving study drug.

  5. Part 1: Number of Participants With One or More Dose Modification due to Adverse Event [ Time Frame: From first dose up to 30 days after last dose ]
    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.

  6. Part 2: Percentage of Participants with Overall Response according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 [ Time Frame: From first dose until discontinuation of study drug due to disease progression, unacceptable toxicity, or death (approximately 1 year) ]
    Overall response is defined as complete response (CR) or partial response (PR) according to RECIST version 1.1 criteria. The estimate of the response rate (RR) will be presented with 2-sided 95 percent (%) exact binomial confidence intervals (CIs) for each treatment arm.


Secondary Outcome Measures :
  1. Number of Participants Reporting One or More Treatment-emergent Adverse Events and Serious Adverse Events [ Time Frame: Baseline up to 30 days after the last dose of study drug (approximately 1 year) ]
    An 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. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. 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; or congenital anomaly; or a medically important event. TEAE is defined as an adverse event with an onset that occurs after receiving study drug.

  2. Percentage of Participants with Dose Delays, Dose Reductions, and Dose Interruptions due to Adverse Events and Serious Adverse Events [ Time Frame: Baseline up to 30 days after the last dose of study drug (approximately 1 year) ]
    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.

  3. Part 2: Progression-free Survival (PFS) [ Time Frame: From first dose until discontinuation of study drug due to disease progression, unacceptable toxicity, or death (approximately 1 year) ]
    Progression-free survival is defined as the time from the date of randomization to the date of first documentation of progressive disease or death due to any cause, whichever occurs first.

  4. Part 2: Percentage of Participants with Disease Control [ Time Frame: From first dose until discontinuation of study drug due to disease progression, unacceptable toxicity, or death (approximately 1 year) ]
    Disease control rate is defined as the percentage of participants with complete response [CR] + partial response [PR] +stable disease [SD] according to RECIST version 1.1 criteria.

  5. Part 2: Duration of Response (DOR) [ Time Frame: From first dose until discontinuation of study drug due to disease progression, unacceptable toxicity, or death (approximately 1 year) ]
    DOR is defined as the time from the date of first documentation of a response to the date of first documentation of PD according to RECIST version 1.1 criteria. Participants without documentation of PD at the time of analysis will be censored at the date of their last response assessment that is SD or better.

  6. Part 2: Time to Disease Progression (TTP) [ Time Frame: From first dose until discontinuation of study drug due to disease progression, unacceptable toxicity, or death (approximately 1 year) ]
    TTP is defined as the time from the date of randomization to the date of first documentation of PD. Participants without documentation of PD at the time of analysis will be censored at the date of their last response assessment that is SD or better. TTP will be analyzed using Kaplan-Meier method.

  7. Part 2: Overall Survival (OS) [ Time Frame: Every 12 weeks until death or 1 year after the last dose of study drug (approximately 1 year) ]
    OS is defined as the time from the date of randomization to the date of death.

  8. Part 1 Cohort A: Cmax- Maximum Observed Plasma Concentration for MLN1117 [ Time Frame: Part 1- Cycle 1 Days 1 and 17: Predose and at multiple time points (up to 24 hours postdose) ]
    Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.

  9. Part 1 Cohort A: Cmax- Maximum Observed Plasma Concentration for TAK-659 [ Time Frame: Part 1- Cycle 1 Days 1 and 17: Predose and at multiple time points (up to 24 hours postdose) ]
    Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.

  10. Part 1 Cohort B: Cmax- Maximum Observed Plasma Concentration for MLN1117 [ Time Frame: Part 1- Cycle 1 Day 3: Predose and at multiple time points (up to 24 hours postdose) ]
    Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.

  11. Part 1 Cohort B: Cmax- Maximum Observed Plasma Concentration for Alisertib [ Time Frame: Part 1- Cycle 1 Day 3: Predose and at multiple time points (up to 24 hours postdose) ]
    Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.

  12. Part 1 Cohort C and Cohort D: Cmax- Maximum Observed Plasma Concentration for MLN1117 [ Time Frame: Part 1- Cycle 1 Day 2: Predose and at multiple time points (up to 24 hours postdose) ]
    Maximum observed plasma concentration (Cmax) is the peak plasma concentration of a drug after administration, obtained directly from the plasma concentration-time curve.

  13. Part 1 Cohort A: Tmax- Time to Reach the Maximum Plasma Concentration (Cmax) for MLN1117 [ Time Frame: Part 1- Cycle 1 Days 1 and 17: Predose and at multiple time points (up to 24 hours postdose) ]
    Tmax: Time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax.

  14. Part 1 Cohort A: Tmax- Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-659 [ Time Frame: Part 1- Cycle 1 Days 1 and 17: Predose and at multiple time points (up to 24 hours postdose) ]
    Tmax: Time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax.

  15. Part 1 Cohort B: Tmax- Time to Reach the Maximum Plasma Concentration (Cmax) for MLN1117 [ Time Frame: Part 1- Cycle 1 Day 3: Predose and at multiple time points (up to 24 hours postdose) ]
    Tmax: Time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax.

  16. Part 1 Cohort B: Tmax- Time to Reach the Maximum Plasma Concentration (Cmax) for Alisertib [ Time Frame: Part 1- Cycle 1 Day 3: Predose and at multiple time points (up to 24 hours postdose) ]
    Tmax: Time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax.

  17. Part 1 Cohort C and Cohort D: Tmax- Time to Reach the Maximum Plasma Concentration (Cmax) for MLN1117 [ Time Frame: Part 1- Cycle 1 Day 2: Predose and at multiple time points (up to 24 hours postdose) ]
    Tmax: Time to reach the maximum plasma concentration (Cmax), equal to time (hours) to Cmax.

  18. Part 1: Cohort A: AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for MLN1117 [ Time Frame: Part 1- Cycle 1 Days 1 and 17: Predose and at multiple time points (up to 24 hours postdose) ]
    AUClast is a measure of total plasma exposure to the drug from Time 0 to Time of the Last Quantifiable Concentration.

  19. Part 1: Cohort A: AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for TAK-659 [ Time Frame: Part 1- Cycle 1 Days 1 and 17: Predose and at multiple time points (up to 24 hours postdose) ]
    AUClast is a measure of total plasma exposure to the drug from Time 0 to Time of the Last Quantifiable Concentration.

  20. Part 1: Cohort B: AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for MLN1117 [ Time Frame: Part 1- Cycle 1 Day 3: Predose and at multiple time points (up to 24 hours postdose) ]
    AUClast is a measure of total plasma exposure to the drug from Time 0 to Time of the Last Quantifiable Concentration.

  21. Part 1: Cohort B: AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for Alisertib [ Time Frame: Part 1- Cycle 1 Day 3: Predose and at multiple time points (up to 24 hours postdose) ]
    AUClast is a measure of total plasma exposure to the drug from Time 0 to Time of the Last Quantifiable Concentration.

  22. Part 1: Cohort C and Cohort D: AUClast: Area Under the Plasma Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration for MLN1117 [ Time Frame: Part 1- Cycle 1 Day 2: Predose and at multiple time points (up to 24 hours postdose) ]
    AUClast is a measure of total plasma exposure to the drug from Time 0 to Time of the Last Quantifiable Concentration.

  23. Part 1 Cohort A: AUC(0-inf)- Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for MLN1117 [ Time Frame: Part 1- Cycle 1 Days 1 and 17: Predose and at multiple time points (up to 24 hours postdose) ]
    AUC (0-inf) is a measure of total plasma exposure to the drug from time zero extrapolated to infinity.

  24. Part 1 Cohort A: AUC(0-inf)- Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for TAK-659 [ Time Frame: Part 1- Cycle 1 Days 1 and 17: Predose and at multiple time points (up to 24 hours postdose) ]
    AUC (0-inf) is a measure of total plasma exposure to the drug from time zero extrapolated to infinity.

  25. Part 1 Cohort B: AUC(0-inf)- Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for MLN1117 [ Time Frame: Part 1- Cycle 1 Day 3: Predose and at multiple time points (up to 24 hours postdose) ]
    AUC (0-inf) is a measure of total plasma exposure to the drug from time zero extrapolated to infinity.

  26. Part 1 Cohort B: AUC(0-inf)- Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for Alisertib [ Time Frame: Part 1- Cycle 1 Day 3: Predose and at multiple time points (up to 24 hours postdose) ]
    AUC (0-inf) is a measure of total plasma exposure to the drug from time zero extrapolated to infinity.

  27. Part 1 Cohort C and Cohort D: AUC(0-inf)- Area Under the Plasma Concentration-time Curve from Time 0 to Infinity for MLN1117 [ Time Frame: Part 1- Cycle 1 Day 2: Predose and at multiple time points (up to 24 hours postdose) ]
    AUC (0-inf) is a measure of total plasma exposure to the drug from time zero extrapolated to infinity.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Part 1 and Part 2

  1. Is male or female aged 18 years or older at the time of consent.
  2. Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 14 days before enrollment.
  3. Has adequate organ and hematologic function as evidenced by the following laboratory values within 14 days before enrollment:

    • Absolute neutrophil count (ANC) ≥1.5x10^9/L.
    • Platelet count ≥100x10^9/L.
    • Hemoglobin ≥9 g/dL (Transfusions are allowed to reach this hemoglobin level).
    • Serum creatinine ≤1.5 times the upper limit of the normal range (ULN) or creatinine clearance ≥50 mL/min either as estimated by the Cockcroft-Gault equation or based on urine collection (12 or 24 hours).
    • Total bilirubin ≤1.5×ULN.
    • Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤2.5×ULN.
  4. Female participants who:

    • Are postmenopausal for at least 1 year before the screening visit, OR
    • Are surgically sterile, OR
    • If they are of childbearing potential, agree to practice 1 highly effective method and 1 additional effective (barrier) method of contraception at the same time, from the time of signing the informed consent form through 30 days after the last dose of study drug (with the exception of those participants assigned to TAK-659, for whom the duration required is 180 days), or for as long as mandated by local labeling for docetaxel and paclitaxel, OR
    • Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant, from the time of signing the informed consent form through 30 days after the last dose of study drug (with the exception of those participants assigned to TAK-659, for whom the duration required is 180 days), or for as long as mandated by local labeling for docetaxel and paclitaxel. (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together.)

    Male participants, even if surgically sterilized (ie, status postvasectomy), who:

    • Agree to practice effective barrier contraception during the entire study treatment period and through 120 days after the last dose of study drug (with the exception of those participants assigned to TAK-659, for whom the duration required is 180 days), or for as long as mandated by local labeling for docetaxel and paclitaxel, OR
    • Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant during the entire study treatment period and through 120 days after the last dose of study drug (with the exception of those participants assigned to TAK-659, for whom the duration required is 180 days) or for as long as mandated by local labeling for docetaxel and paclitaxel. (Periodic abstinence [eg, calendar, ovulation, symptothermal, postovulation methods for the female partner] and withdrawal are not acceptable methods of contraception.)
  5. Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the participant at any time without prejudice to future medical care.
  6. Has suitable venous access for the study-required blood sampling (ie, pharmacokinetic (PK) sampling, circulating tumor deoxyribonucleic acid [DNA]).

Part 1 only

  1. Has a histologically confirmed diagnosis of advanced solid tumor, including but not limited to gastric or gastroesophageal junction adenocarcinoma.
  2. Has radiographically or clinically evaluable disease. Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST), Version 1.1 is not required.
  3. Is relapsed or refractory with no effective therapeutic options available.

Part 2 only

  1. Has a histologically confirmed diagnosis of metastatic or locally advanced adenocarcinoma of the stomach or gastroesophageal junction (Stage IIIb or IV according to International Union Against Cancer [UICC] tumor, node, metastases [TNM] classification, 7th edition).
  2. Has at least 1 measurable tumor lesion per RECIST Version 1.1 by radiographic techniques (computed tomography [CT] or magnetic resonance imaging [MRI]).
  3. Has receipt of 1 prior systemic chemotherapy regimen for advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction with documented progressive disease (PD).
  4. Has archived or fresh tumor biopsy samples obtained during screening sufficient for Epstein-Barr virus (EBV) testing and genotyping.

Exclusion Criteria:

Part 1 and Part 2

  1. Has received prior systemic anticancer therapies or other investigational agents within 2 weeks before the first administration of study drug or has failed to recover from the adverse drug effects of prior therapies (to ≤Grade 1 or to a level meeting inclusion criteria). For prior therapies with a half-life longer than 3 days, the interval must equal minimally 28 days before the first administration of study drug and the participant must have documented PD.
  2. Has radiotherapy within 14 days before enrollment.
  3. Has fasting glucose ≥130 mg/dL. Poorly controlled diabetes mellitus (glycosylated hemoglobin [HbA1c] >7.0%). Participants with a history of transient glucose intolerance due to corticosteroid administration are allowed.
  4. Has received strong cytochrome P-450 (CYP) 3A4 inducers/inhibitors within 7 days before the first administration of study drug or has conditions that require the concomitant use of CYP3A4 inducers/inhibitors during the course of the study.
  5. For TAK-659 (Cohort A) only: Is receiving treatment with medications that are known to be inhibitors or inducers of P-glycoprotein (P-gp). Baseline lipase >ULN. Participants not fulfilling these exclusion criteria can be enrolled in other cohorts (Part 1 only).
  6. Has taken proton pump inhibitors within 7 days before the first administration of study drug or has conditions that require the concomitant use of proton pump inhibitors during the course of the study.
  7. Has signs of peripheral neuropathy ≥ National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade 2.
  8. Has symptomatic brain metastases or brain metastases with a stable neurologic status for <2 weeks after completion of the definitive therapy and steroids.
  9. Has systemic infection requiring intravenous (IV) antibiotic therapy or other serious infection within 14 days before the first dose of study drug.
  10. Has known or suspected human immunodeficiency virus (HIV) positive or hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection. Testing for these agents is not required in the absence of clinical findings or suspicion.
  11. Has known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerability of orally administered study drug, including difficulty swallowing tablets; diarrhea >Grade 1 despite supportive therapy; or prior total gastrectomy.
  12. Has clinically significant comorbidities, such as uncontrolled pulmonary disease, known impaired cardiac function or clinically significant cardiac disease, active central nervous system disease, or any other condition that could compromise the participant's participation in the study.

    • Known impaired cardiac function or clinically significant cardiac disease includes: evidence of currently uncontrolled cardiovascular conditions (including arrhythmias, angina, pulmonary hypertension, acute ischemia or active conduction system abnormalities); current history of New York Heart Association Class III or IV heart failure; acute myocardial infarction within 6 months before starting study drug; baseline QT interval corrected for heart rate (QTc) ≥Grade 1 according to NCI CTCAE Version 4.03 criteria; or abnormalities on baseline 12-lead ECG that are considered clinically significant per the investigator.

  13. Female participants who are lactating and breastfeeding or have a positive serum pregnancy test during the screening period or a positive urine pregnancy test on Day 1 before the first dose of study drug.
  14. Participants with bilirubin >ULN, or AST and/or ALT >1.5 X ULN concomitant with alkaline phosphatase >2.5 X ULN cannot be allocated to Cohort D (MLN1117+docetaxel) in Part 1 and are not eligible for Part 2 if they are also EBV negative.

Part 2 only

1. Has prior treatment with any of the following:

  • An Aurora A-targeted agent (not eligible for randomization in Cohorts B, C, or D, but eligible for Cohort A if EBV positive).
  • A docetaxel- or paclitaxel-containing chemotherapy regimen (not eligible for randomization in Cohorts B, C, or D, but eligible for Cohort A if EBV positive).
  • A spleen tyrosine kinase (SYK) inhibitor (MLN1117+TAK-659 arm only).
  • A phosphoinositide 3-kinase (PI3K) or serine/threonine kinase, also known as protein kinase B or PKB (AKT) inhibitor.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02551055


Locations
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United States, New York
Lake Success, New York, United States
New York, New York, United States
United States, Pennsylvania
Philadelphia, Pennsylvania, United States
United States, Texas
Dallas, Texas, United States
Houston, Texas, United States
Spain
Barcelona, Spain
Sponsors and Collaborators
Millennium Pharmaceuticals, Inc.
Investigators
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Study Director: Medical Director Takeda

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Responsible Party: Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02551055     History of Changes
Other Study ID Numbers: C032-6001 (MLN1117-1003)
2015-001032-38 ( EudraCT Number )
U1111-1166-8653 ( Registry Identifier: WHO )
REec-2016-2039 ( Other Identifier: REEC )
First Posted: September 16, 2015    Key Record Dates
Last Update Posted: August 17, 2017
Last Verified: August 2017

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Takeda ( Millennium Pharmaceuticals, Inc. ):
Drug Therapy

Additional relevant MeSH terms:
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Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Paclitaxel
Docetaxel
Albumin-Bound Paclitaxel
Antineoplastic Agents
Serabelisib
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors