A Study of Sapanisertib, Combination of Sapanisertib With MLN1117, Paclitaxel and Combination of Sapanisertib With Paclitaxel in Women With Endometrial Cancer
A Phase 2, Randomized Study of MLN0128 (a Dual TORC1/2 Inhibitor), MLN0128+MLN1117 (a PI3Kα Inhibitor), Weekly Paclitaxel, or the Combination of Weekly Paclitaxel and MLN0128 in Women With Advanced, Recurrent, or Persistent Endometrial Cancer
4 other identifiers
interventional
241
10 countries
78
Brief Summary
The primary purpose of this study is to determine if sapanisertib in combination with weekly paclitaxel improves progression-free survival (PFS) compared to weekly paclitaxel alone.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Apr 2016
Typical duration for phase_2
78 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 28, 2016
CompletedFirst Posted
Study publicly available on registry
March 31, 2016
CompletedStudy Start
First participant enrolled
April 1, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 2, 2019
CompletedResults Posted
Study results publicly available
June 9, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
October 30, 2020
CompletedNovember 24, 2021
October 1, 2021
3.3 years
March 28, 2016
May 22, 2020
October 28, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progression Free Survival (PFS)
PFS is defined as the time in months from the date of randomization to the date of first documentation of progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST v1.1, PD was defined as at least a 20% increase in the sum of the longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Up to approximately 30 months
Secondary Outcomes (6)
Number of Participants Who Experienced at Least One Treatment-emergent Adverse Event (TEAE)
From the first dose of study drug through 30 days after the last dose of study drug (Up to approximately 54 months)
Overall Survival (OS)
Up to approximately 54 months
Time to Tumor Progression (TTP)
Up to 30 months
Overall Response Rate (ORR)
Up to 30 months
Clinical Benefit Rate (CBR)
Up to 30 months
- +1 more secondary outcomes
Study Arms (4)
Paclitaxel 80 mg/m^2
EXPERIMENTALPaclitaxel 80 milligrams per square meter (mg/m\^2), IV, weekly on Days 1, 8, and 15 of a 28-day cycle until disease progression, unacceptable toxicity, or withdraw consent (the median exposure was up to approximately 13 weeks).
Paclitaxel 80 mg/m^2 + Sapanisertib 4 mg
EXPERIMENTALPaclitaxel 80 mg/m\^2, IV, weekly on Days 1, 8, and 15 of a 28-day cycle along with sapanisertib 4 milligrams (mg), capsule, orally on Days 2-4, 9-11, 16-18, and 23-25 of a 28-day cycle until disease progression, unacceptable toxicity, or withdraw consent (the median exposure was up to approximately 20 weeks).
Sapanisertib 30 mg
EXPERIMENTALSapanisertib 30 mg, capsule, orally, once weekly on Days 1, 8, 15, and 22 of a 28-day cycle until disease progression, unacceptable toxicity, or withdraw consent (the median exposure was up to approximately 6 weeks).
Sapanisertib 4 mg + MLN1117 200 mg
EXPERIMENTALSapanisertib 4 mg, capsule, orally and MLN1117 200 mg, capsule, orally on Days 1-3, 8-10, 15-17, and 22-24 of a 28-day cycle until disease progression, unacceptable toxicity, or withdraw consent (the median exposure was up to approximately 8 weeks).
Interventions
Paclitaxel intravenous solution.
Sapanisertib capsules.
Eligibility Criteria
You may qualify if:
- Histologic or cytologic diagnosis of endometrial carcinoma (including endometrioid, serous, mixed adenocarcinoma, clear-cell carcinoma, or carcinosarcoma).
- Evidence that the endometrial cancer is advanced, recurrent, or persistent and has relapsed or is refractory to curative therapy or established treatments.
- At least 1 prior platinum-based chemotherapeutic regimen, but not more than 2 prior chemotherapeutic regimens, for management of endometrial carcinoma. Prior treatment may include chemotherapy, chemotherapy/radiation therapy, and/or consolidation/maintenance therapy. Chemotherapy administered in conjunction with primary radiation as a radio-sensitized therapy will be considered a systemic chemotherapy regimen.
- Measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, defined as at least 1 lesion that can be accurately measured in at least 1 dimension (longest diameter to be recorded). Each lesion must be greater than or equal to (\>=) 10 millimeter (mm) in long axis when measured by computed tomography (CT), magnetic resonance imaging (MRI), or caliper measurement by clinical exam. Lymph nodes must be \>= 15 mm in short axis when measured by CT or MRI.
- Tumor accessible and participant consents to undergo fresh tumor biopsies.
- Female participants 18 years or older.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
- 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 of contraception and 1 additional effective (barrier) method at the same time, from the time of signing the informed consent through 90 days (or longer, as mandated by local labeling \[example, United States Prescribing Information (USPI), Summary of Product Characteristics (SmPC), etc.\]) after the last dose of study drug, OR
- Agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant. (Periodic abstinence \[example, calendar, ovulation, symptothermal, postovulation methods\], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together.)
- Clinical laboratory values as specified below within 4 weeks before the first dose of study drug:
- Bone marrow reserve consistent with absolute neutrophil count (ANC) \>= 1500 per micro liter (/mcL); platelet count \>= 100,000/mcL; hemoglobin A1c (HbA1c) less than (\<) 6.5 percent (%).
- Total bilirubin must be less than or equal to (\<=) 1.5 \* the upper limit of normal (ULN).
- +5 more criteria
You may not qualify if:
- Positive serum pregnancy test during the screening period or a positive urine pregnancy test on Day 1 before first dose of study drug. Women who are lactating and breastfeeding are not eligible.
- Previous treatment with any weekly taxane regimen.
- History of severe hypersensitivity reactions to paclitaxel or any of its excipients.
- Previous treatment with phosphoinositide 3-kinase (PI3K), serine/threonine-specific protein kinase (AKT), dual PI3K/ mammalian (or mechanistic) target of rapamycin (mTOR) inhibitors, target of rapamycin complex 1/2 (TORC1/2) inhibitors or TORC1 inhibitors.
- Initiation of treatment with hematopoietic growth factors, transfusions of blood and blood products, or systemic corticosteroids (either intravenous \[IV\] or oral steroids, excluding inhalers) within 1 week before administration of the first dose of study drug (participants already receiving erythropoietin on a chronic basis for \>=4 weeks are eligible).
- Participants who are taking proton pump inhibitors (PPIs) within 7 days of the first dose of study drug or who require treatment with PPIs throughout the trial or those who are taking H2 receptor antagonists within 24 hours of the first dose of study drug.
- A prothrombin time (PT) or activated partial thromboplastin time (aPTT) above the ULN or a history of a coagulopathy or bleeding disorder.
- Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C infection.
- Sensory or motor neuropathy \>= Grade 2.
- Central nervous system (CNS) metastasis, endometrial leiomyosarcoma, or endometrial stromal sarcoma.
- Manifestations of malabsorption due to prior gastrointestinal surgery, gastrointestinal disease, or for some other reason that may alter the absorption of sapanisertib or MLN1117. In addition, participants with enteric stomata are also excluded.
- Other clinically significant co-morbidities, such as uncontrolled pulmonary disease, active CNS disease, active infection, or any other condition that could compromise participation of the participant in the study.
- Known human immunodeficiency virus infection.
- History of any of the following within the last 6 months before administration of the first dose of study drug:
- Ischemic myocardial event, including angina requiring therapy and artery revascularization procedures.
- +15 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (78)
University of Alabama Comprehensive Cancer Center
Birmingham, Alabama, 35294-3300, United States
University of Arizona Cancer Center
Phoenix, Arizona, 85013, United States
Marin Cancer Care
Greenbrae, California, 94904, United States
University of California San Diego Medical Center
La Jolla, California, 92093-1503, United States
University of California at San Francisco (PARENT)
San Francisco, California, 94115, United States
Stanford School of Medicine
Stanford, California, 94305, United States
H. Lee Moffitt Cancer Center and Research Institute, Inc
Tampa, Florida, 33612-9416, United States
Florida Cancer Specialists
West Palm Beach, Florida, 33401, United States
Augusta University
Augusta, Georgia, 30912, United States
Franciscan St. Francis Health
Indianapolis, Indiana, 46237, United States
University of Kansas Medical Center Research Institute, Inc.
Westwood, Kansas, 66205, United States
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114, United States
Washington University
St Louis, Missouri, 63108, United States
NYU Langone Medical Center Clinic
New York, New York, 10016, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065-6094, United States
Levine Cancer Institute
Charlotte, North Carolina, 28204, United States
Oklahoma University Health Sciences Center
Oklahoma City, Oklahoma, 73104, United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111, United States
University of Pittsburgh Medical Center Cancer Center at Magee-Womens Hospital
Pittsburgh, Pennsylvania, 15232, United States
Sarah Cannon Research Institute
Nashville, Tennessee, 37203, United States
University of Texas Southwestern Medical Center
Dallas, Texas, 75390, United States
St George Hospital
Kogarah, New South Wales, 2217, Australia
Westmead Hospital
Westmead, New South Wales, 2145, Australia
Royal Brisbane and Women's Hospital
Herston, Queensland, 4029, Australia
Monash Medical Centre Clayton
Clayton, Victoria, 3168, Australia
Sunshine Hospital
Footscray, Victoria, 3011, Australia
Cabrini Hospital Malvern
Malvern, Victoria, 3144, Australia
Peter MacCallum Cancer Centre-East Melbourne
Melbourne, Victoria, 3000, Australia
UZ Antwerpen
Edegem, Antwerpen, 2650, Belgium
Cliniques Universitaires Saint-Luc
Brussels, 1200, Belgium
UZ Leuven
Leuven, 3000, Belgium
Centre Hospitalier Universitaire de Liege Site Sart Tilman
Liège, 4000, Belgium
GasthuisZusters Antwerpen Sint-Augustinus
Wilrijk, 2610, Belgium
Tom Baker Cancer Centre
Calgary, Alberta, T2N 4N2, Canada
Juravinski Cancer Clinic
Hamilton, Ontario, L8V 5C2, Canada
LHSC - Victoria Hospital
London, Ontario, N6A 4L6, Canada
Ottawa Hospital Cancer Centre
Ottawa, Ontario, K1H 8L6, Canada
University Health Network - Princess Margaret Cancer Centre
Toronto, Ontario, M5G 2M9, Canada
CHUM Hopital Notre-Dame
Montreal, Quebec, H2X 3E4, Canada
Medizinische Hochschule Hannover
Hanover, Lower Saxony, 30625, Germany
Universitaetsmedizin Greifswald
Greifswald, Mecklenburg-Vorpommern, 17489, Germany
Universitaetsklinikum Carl Gustav Carus TU Dresden
Dresden, Saxony, 01307, Germany
Universitaetsklinikum Schleswig-Holstein - Campus Luebeck
Lübeck, Schleswig-Holstein, 23538, Germany
Charite - Universitaetsmedizin Berlin - Campus Virchow-Klinikum
Berlin, 13353, Germany
Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori
Meldola, Forli - Cesena, 47014, Italy
Spedali Civili di Brescia
Brescia, 25123, Italy
Ente Ospedaliero Ospedali Galliera
Genova, 16128, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan, 20133, Italy
IEO Istituto Europeo di Oncologia
Milan, 20141, Italy
Istituto Tumori Napoli Fondazione G. Pascale
Napoli, 80131, Italy
Azienda Unita Sanitaria Locale di Ravenna
Ravenna, 48121, Italy
Istituto Nationale Tumori Regina Elena
Roma, 00144, Italy
Universita degli Studi di Roma "La Sapienza" - Umberto I Policlinico di Roma
Roma, 00161, Italy
Fondazione Policlinico Universitario Agostino Gemelli
Roma, 00168, Italy
Maastricht Universitair Medisch Centrum
Maastricht, Limburg, 6229 HX, Netherlands
Academisch Medisch Centrum
Amsterdam, North Holland, 1105 AZ, Netherlands
Erasmus Medisch Centrum Daniel den Hoed
Rotterdam, South Holland, 3015 GD, Netherlands
Universitair Medisch Centrum Groningen
Groningen, 9700 RB, Netherlands
Universitair Medisch Centrum Utrecht
Utrecht, 3584 CX, Netherlands
Haukeland universitetssykehus, Kvinneklinikken
Bergen, 5021, Norway
Radiumhospitalet
Oslo, 0310, Norway
Stavanger University Hospital
Stavanger, 4011, Norway
Hospital Universitari Vall d'Hebron
Barcelona, 08035, Spain
MD Anderson Cancer Centre
Madrid, 28033, Spain
Hospital Universitario Ramon y Cajal
Madrid, 28034, Spain
Hospital Universitario Clinico San Carlos
Madrid, 28040, Spain
Hospital Universitario La Paz
Madrid, 28046, Spain
Centro Integral Oncologico Clara Campal
Madrid, 28050, Spain
Instituto Valenciano de Oncologia IVO
Valencia, 46009, Spain
Bristol Haematology and Oncology Centre
Bristol, Avon, BS2 8ED, United Kingdom
Royal Devon and Exeter Hospital (Wonford)
Exeter, Devon, EX2 5DW, United Kingdom
University College London Hospitals
London, Greater London, NW1 2BU, United Kingdom
Royal Marsden Hospital
London, Greater London, SW3 6JJ, United Kingdom
Hammersmith Hospital
London, Greater London, W12 0HS, United Kingdom
The Christie
Manchester, Greater Manchester, M20 4BX, United Kingdom
Royal Marsden Hospital
Sutton, Surrey, SM2 5PT, United Kingdom
University Hospital Coventry
Coventry, CV2 2DX, United Kingdom
Beatson West of Scotland Cancer Centre
Glasgow, G12 0YN, United Kingdom
Related Publications (1)
Han SN, Oza A, Colombo N, Oaknin A, Raspagliesi F, Wenham RM, Braicu EI, Jewell A, Makker V, Krell J, Alia EMG, Baurain JF, Su Z, Neuwirth R, Vincent S, Sedarati F, Faller DV, Scambia G. A randomized phase 2 study of sapanisertib in combination with paclitaxel versus paclitaxel alone in women with advanced, recurrent, or persistent endometrial cancer. Gynecol Oncol. 2023 Nov;178:110-118. doi: 10.1016/j.ygyno.2023.09.013. Epub 2023 Oct 14.
PMID: 37839313DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Director
- Organization
- Takeda
Study Officials
- STUDY DIRECTOR
Medical Director Clinical Science
Millennium Pharmaceuticals, Inc.
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 28, 2016
First Posted
March 31, 2016
Study Start
April 1, 2016
Primary Completion
July 2, 2019
Study Completion
October 30, 2020
Last Updated
November 24, 2021
Results First Posted
June 9, 2020
Record last verified: 2021-10
Data Sharing
- IPD Sharing
- Will share
Takeda makes patient-level, de-identified data sets and associated documents available for all interventional studies after applicable marketing approvals and commercial availability have been received (or program is completely terminated), an opportunity for the primary publication of the research and final report development has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.