A Study of Sapanisertib, Combination of Sapanisertib With MLN1117, Paclitaxel and Combination of Sapanisertib With Paclitaxel in Women With Endometrial Cancer
NCT ID: NCT02725268
Last Updated: 2021-11-24
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE2
241 participants
INTERVENTIONAL
2016-04-01
2020-10-30
Brief Summary
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Detailed Description
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The study will enroll approximately 241 participants. Participants will be randomly assigned (by chance, like flipping a coin) to one of 4 treatment groups:
* Paclitaxel 80 mg/m\^2
* Paclitaxel 80 mg/m\^2 + Sapanisertib 4 mg
* Sapanisertib 30 mg
* Sapanisertib 4 mg + MLN1117 200 mg
Participants will receive either paclitaxel intravenous (IV) weekly, Paclitaxel IV along with sapanisertib orally, sapanisertib orally, or sapanisertib and MLN1117 orally.
This is a multicenter, multinational trial. Participants will make multiple visits to the clinic, with an end of treatment visit (EOT) which will occur 30 to 40 days after receiving their last dose of study drug or before the start of any subsequent anticancer therapy. After EOT, participants will be followed for PFS and overall survival (OS).
Conditions
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Paclitaxel 80 mg/m^2
Paclitaxel 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
Paclitaxel intravenous solution.
Paclitaxel 80 mg/m^2 + Sapanisertib 4 mg
Paclitaxel 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).
Paclitaxel
Paclitaxel intravenous solution.
Sapanisertib
Sapanisertib capsules.
Sapanisertib 30 mg
Sapanisertib 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
Sapanisertib capsules.
Sapanisertib 4 mg + MLN1117 200 mg
Sapanisertib 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).
Sapanisertib
Sapanisertib capsules.
MLN1117
MLN1117 capsules.
Interventions
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Paclitaxel
Paclitaxel intravenous solution.
Sapanisertib
Sapanisertib capsules.
MLN1117
MLN1117 capsules.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. Evidence that the endometrial cancer is advanced, recurrent, or persistent and has relapsed or is refractory to curative therapy or established treatments.
3. 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.
4. 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.
5. Tumor accessible and participant consents to undergo fresh tumor biopsies.
6. Female participants 18 years or older.
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
8. 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.)
9. 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).
* Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) must be \<= 2.5 \* the upper limit of the normal range. AST and ALT may be elevated up to 5 times the ULN if their elevation can be reasonably ascribed to the presence of metastatic disease in liver.
* Creatinine clearance \>= 50 milliliter per minute per 1.73 square meter (mL/min/1.73 m\^2) based either on Cockcroft-Gault estimate or based on a 12- or 24-hour urine collection.
* Fasting serum glucose \< 130 milligram per deciliter (mg/dL) and fasting triglycerides \<= 300 mg/dL.
10. Ability to swallow oral medications, willingness to perform mucositis prophylaxis, and suitable venous access for the study-required blood sampling.
11. 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.
Exclusion Criteria
2. Previous treatment with any weekly taxane regimen.
3. History of severe hypersensitivity reactions to paclitaxel or any of its excipients.
4. 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.
5. 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).
6. 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.
7. A prothrombin time (PT) or activated partial thromboplastin time (aPTT) above the ULN or a history of a coagulopathy or bleeding disorder.
8. Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C infection.
9. Sensory or motor neuropathy \>= Grade 2.
10. Central nervous system (CNS) metastasis, endometrial leiomyosarcoma, or endometrial stromal sarcoma.
11. 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.
12. 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.
13. Known human immunodeficiency virus infection.
14. 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.
* Ischemic cerebrovascular event, including transient ischemic attack and artery revascularization procedures.
* Requirement for inotropic support (excluding digoxin) or serious (uncontrolled) cardiac arrhythmia (including atrial flutter/fibrillation, ventricular fibrillation, or ventricular tachycardia).
* Placement of a pacemaker for control of rhythm.
* New York Heart Association Class III or IV heart failure.
* Pulmonary embolism.
15. Significant active cardiovascular or pulmonary disease before administration of the first dose of study drug, including:
* Uncontrolled hypertension (that is, either systolic blood pressure \> 180 millimeter of mercury \[mm Hg\] or diastolic blood pressure \> 95 mm Hg).
* Pulmonary hypertension.
* Uncontrolled asthma or oxygen saturation \< 90% by arterial blood gas analysis or pulse oximetry on room air.
* Significant valvular disease; severe regurgitation or stenosis by imaging independent of symptom control with medical intervention; or history of valve replacement.
* Medically significant (symptomatic) bradycardia.
* History of arrhythmia requiring an implantable cardiac defibrillator.
* Baseline prolongation of the rate-corrected QT interval (QTc; example, repeated demonstration of QTc interval \> 480 millisecond \[ms\], or history of congenital long QT syndrome, or torsades de pointes).
16. Diagnosed or treated for another malignancy within 2 years before administration of the first dose of study drug or previously diagnosed with another malignancy and have any evidence of residual disease. Participants with non-melanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
17. Participants with endometrioid histology and histologically confirmed expression of estrogen receptors (ER) and/or progesterone receptors (PgR) who have not received prior endocrine therapy and for whom endocrine therapy is currently indicated.
18 Years
FEMALE
No
Sponsors
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European Network of Translational Research in Ovarian Cancer - EUTROC
UNKNOWN
European Network of Individualized Treatment in Endometrial Cancer - ENITEC
OTHER_GOV
Millennium Pharmaceuticals, Inc.
INDUSTRY
Responsible Party
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Principal Investigators
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Medical Director Clinical Science
Role: STUDY_DIRECTOR
Millennium Pharmaceuticals, Inc.
Locations
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University of Alabama Comprehensive Cancer Center
Birmingham, Alabama, United States
University of Arizona Cancer Center
Phoenix, Arizona, United States
Marin Cancer Care
Greenbrae, California, United States
University of California San Diego Medical Center
La Jolla, California, United States
University of California at San Francisco (PARENT)
San Francisco, California, United States
Stanford School of Medicine
Stanford, California, United States
H. Lee Moffitt Cancer Center and Research Institute, Inc
Tampa, Florida, United States
Florida Cancer Specialists
West Palm Beach, Florida, United States
Augusta University
Augusta, Georgia, United States
Franciscan St. Francis Health
Indianapolis, Indiana, United States
University of Kansas Medical Center Research Institute, Inc.
Westwood, Kansas, United States
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, United States
Washington University
St Louis, Missouri, United States
NYU Langone Medical Center Clinic
New York, New York, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
Levine Cancer Institute
Charlotte, North Carolina, United States
Oklahoma University Health Sciences Center
Oklahoma City, Oklahoma, United States
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States
University of Pittsburgh Medical Center Cancer Center at Magee-Womens Hospital
Pittsburgh, Pennsylvania, United States
Sarah Cannon Research Institute
Nashville, Tennessee, United States
University of Texas Southwestern Medical Center
Dallas, Texas, United States
St George Hospital
Kogarah, New South Wales, Australia
Westmead Hospital
Westmead, New South Wales, Australia
Royal Brisbane and Women's Hospital
Herston, Queensland, Australia
Monash Medical Centre Clayton
Clayton, Victoria, Australia
Sunshine Hospital
Footscray, Victoria, Australia
Cabrini Hospital Malvern
Malvern, Victoria, Australia
Peter MacCallum Cancer Centre-East Melbourne
Melbourne, Victoria, Australia
UZ Antwerpen
Edegem, Antwerpen, Belgium
Cliniques Universitaires Saint-Luc
Brussels, , Belgium
UZ Leuven
Leuven, , Belgium
Centre Hospitalier Universitaire de Liege Site Sart Tilman
Liège, , Belgium
GasthuisZusters Antwerpen Sint-Augustinus
Wilrijk, , Belgium
Tom Baker Cancer Centre
Calgary, Alberta, Canada
Juravinski Cancer Clinic
Hamilton, Ontario, Canada
LHSC - Victoria Hospital
London, Ontario, Canada
Ottawa Hospital Cancer Centre
Ottawa, Ontario, Canada
University Health Network - Princess Margaret Cancer Centre
Toronto, Ontario, Canada
CHUM Hopital Notre-Dame
Montreal, Quebec, Canada
Medizinische Hochschule Hannover
Hanover, Lower Saxony, Germany
Universitaetsmedizin Greifswald
Greifswald, Mecklenburg-Vorpommern, Germany
Universitaetsklinikum Carl Gustav Carus TU Dresden
Dresden, Saxony, Germany
Universitaetsklinikum Schleswig-Holstein - Campus Luebeck
Lübeck, Schleswig-Holstein, Germany
Charite - Universitaetsmedizin Berlin - Campus Virchow-Klinikum
Berlin, , Germany
Istituto Scientifico Romagnolo Per Lo Studio e La Cura Dei Tumori
Meldola, Forli - Cesena, Italy
Spedali Civili di Brescia
Brescia, , Italy
Ente Ospedaliero Ospedali Galliera
Genova, , Italy
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan, , Italy
IEO Istituto Europeo di Oncologia
Milan, , Italy
Istituto Tumori Napoli Fondazione G. Pascale
Napoli, , Italy
Azienda Unita Sanitaria Locale di Ravenna
Ravenna, , Italy
Istituto Nationale Tumori Regina Elena
Roma, , Italy
Universita degli Studi di Roma "La Sapienza" - Umberto I Policlinico di Roma
Roma, , Italy
Fondazione Policlinico Universitario Agostino Gemelli
Roma, , Italy
Maastricht Universitair Medisch Centrum
Maastricht, Limburg, Netherlands
Academisch Medisch Centrum
Amsterdam, North Holland, Netherlands
Erasmus Medisch Centrum Daniel den Hoed
Rotterdam, South Holland, Netherlands
Universitair Medisch Centrum Groningen
Groningen, , Netherlands
Universitair Medisch Centrum Utrecht
Utrecht, , Netherlands
Haukeland universitetssykehus, Kvinneklinikken
Bergen, , Norway
Radiumhospitalet
Oslo, , Norway
Stavanger University Hospital
Stavanger, , Norway
Hospital Universitari Vall d'Hebron
Barcelona, , Spain
MD Anderson Cancer Centre
Madrid, , Spain
Hospital Universitario Ramon y Cajal
Madrid, , Spain
Hospital Universitario Clinico San Carlos
Madrid, , Spain
Hospital Universitario La Paz
Madrid, , Spain
Centro Integral Oncologico Clara Campal
Madrid, , Spain
Instituto Valenciano de Oncologia IVO
Valencia, , Spain
Bristol Haematology and Oncology Centre
Bristol, Avon, United Kingdom
Royal Devon and Exeter Hospital (Wonford)
Exeter, Devon, United Kingdom
University College London Hospitals
London, Greater London, United Kingdom
Royal Marsden Hospital
London, Greater London, United Kingdom
Hammersmith Hospital
London, Greater London, United Kingdom
The Christie
Manchester, Greater Manchester, United Kingdom
Royal Marsden Hospital
Sutton, Surrey, United Kingdom
University Hospital Coventry
Coventry, , United Kingdom
Beatson West of Scotland Cancer Centre
Glasgow, , United Kingdom
Countries
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References
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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.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Other Identifiers
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U1111-1168-1824
Identifier Type: OTHER
Identifier Source: secondary_id
2014-005394-37
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
02725268
Identifier Type: REGISTRY
Identifier Source: secondary_id
C31004
Identifier Type: -
Identifier Source: org_study_id