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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT02725268
Registration number
NCT02725268
Ethics application status
Date submitted
28/03/2016
Date registered
31/03/2016
Date last updated
24/11/2021
Titles & IDs
Public title
A Study of Sapanisertib, Combination of Sapanisertib With MLN1117, Paclitaxel and Combination of Sapanisertib With Paclitaxel in Women With Endometrial Cancer
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Scientific title
A Phase 2, Randomized Study of MLN0128 (a Dual TORC1/2 Inhibitor), MLN0128+MLN1117 (a PI3Ka Inhibitor), Weekly Paclitaxel, or the Combination of Weekly Paclitaxel and MLN0128 in Women With Advanced, Recurrent, or Persistent Endometrial Cancer
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Secondary ID [1]
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U1111-1168-1824
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Secondary ID [2]
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C31004
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Endometrial Neoplasms
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Condition category
Condition code
Cancer
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Womb (Uterine or endometrial cancer)
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Paclitaxel
Treatment: Drugs - Sapanisertib
Treatment: Drugs - MLN1117
Experimental: 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).
Experimental: 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).
Experimental: 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).
Experimental: 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).
Treatment: Drugs: Paclitaxel
Paclitaxel intravenous solution.
Treatment: Drugs: Sapanisertib
Sapanisertib capsules.
Treatment: Drugs: MLN1117
MLN1117 capsules.
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Progression Free Survival (PFS)
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Assessment method [1]
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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.
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Timepoint [1]
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Up to approximately 30 months
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Secondary outcome [1]
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Number of Participants Who Experienced at Least One Treatment-emergent Adverse Event (TEAE)
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Assessment method [1]
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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 TEAE is defined as an adverse event with an onset that occurs after receiving study drug.
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Timepoint [1]
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From the first dose of study drug through 30 days after the last dose of study drug (Up to approximately 54 months)
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Secondary outcome [2]
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Overall Survival (OS)
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Assessment method [2]
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OS is defined as the time in months from the date of randomization to the date of death.
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Timepoint [2]
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Up to approximately 54 months
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Secondary outcome [3]
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Time to Tumor Progression (TTP)
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Assessment method [3]
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TTP is defined as the time in months from the date of randomization to the date of first documentation of progression. Per RECIST 1.1, 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.
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Timepoint [3]
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Up to 30 months
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Secondary outcome [4]
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Overall Response Rate (ORR)
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Assessment method [4]
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ORR is defined as the percentage of participants who achieved a best response of a complete response (CR) or partial response (PR). Per RECIST v1.1, CR was defined as disappearance of all target lesions, non-target lesions, no new lesions, and normalization of tumor marker level. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, no progression in non-target lesion, and no new lesions.
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Timepoint [4]
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Up to 30 months
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Secondary outcome [5]
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Clinical Benefit Rate (CBR)
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Assessment method [5]
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CBR is defined as the percentage of participants with CR or PR or SD (SD of any duration). Per RECIST v1.1, CR was defined as disappearance of all target lesions, non-target lesions, no new lesions, and normalization of tumor marker level. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, no progression in non-target lesion, and no new lesions. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. 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.
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Timepoint [5]
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Up to 30 months
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Secondary outcome [6]
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Clinical Benefit Rate (CBR) at Week 16 (CBR-16)
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Assessment method [6]
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CBR-16 is defined as the percentage of participants who achieved CR or PR of any duration or have SD with a duration of at least 16 weeks. Per RECIST v1.1, CR was defined as disappearance of all target lesions, non-target lesions, no new lesions, and normalization of tumor marker level. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, no progression in non-target lesion, and no new lesions. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. 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.
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Timepoint [6]
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Week 16
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Eligibility
Key inclusion criteria
1. Histologic or cytologic diagnosis of endometrial carcinoma (including endometrioid,
serous, mixed adenocarcinoma, clear-cell carcinoma, or carcinosarcoma).
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.
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Females
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Can healthy volunteers participate?
No
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Key exclusion criteria
1. 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.
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.
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 2
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
1/04/2016
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
30/10/2020
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Sample size
Target
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Accrual to date
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Final
241
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Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
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Recruitment hospital [1]
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St George Hospital - Kogarah
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Recruitment hospital [2]
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Westmead Hospital - Westmead
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Royal Brisbane and Women's Hospital - Herston
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Monash Medical Centre Clayton - Clayton
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Sunshine Hospital - Footscray
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Cabrini Hospital Malvern - Malvern
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Recruitment hospital [7]
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Peter MacCallum Cancer Centre-East Melbourne - Melbourne
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Recruitment postcode(s) [1]
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2217 - Kogarah
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Recruitment postcode(s) [2]
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2145 - Westmead
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Recruitment postcode(s) [3]
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4029 - Herston
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Recruitment postcode(s) [4]
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3168 - Clayton
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3011 - Footscray
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3144 - Malvern
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Recruitment postcode(s) [7]
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3000 - Melbourne
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Recruitment outside Australia
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United States of America
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Alabama
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Arizona
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Kansas
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Massachusetts
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North Carolina
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Texas
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Belgium
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Antwerpen
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Canada
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Ontario
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Mecklenburg Vorpommern
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Germany
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Niedersachsen
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Germany
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Sachsen
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Germany
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Schleswig Holstein
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Germany
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Berlin
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Italy
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Forli - Cesena
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Italy
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Brescia
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Italy
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Genova
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Italy
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Milano
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Italy
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Napoli
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Italy
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Italy
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Utrecht
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Oslo
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Stavanger
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Spain
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Barcelona
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Spain
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Madrid
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Spain
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Valencia
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United Kingdom
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Avon
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Devon
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Greater London
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Greater Manchester
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Coventry
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United Kingdom
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Glasgow
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
Millennium Pharmaceuticals, Inc.
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Address
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Other collaborator category [1]
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Other
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Name [1]
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European Network of Translational Research in Ovarian Cancer - EUTROC
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Other
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Name [2]
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European Network of Individualized Treatment in Endometrial Cancer - ENITEC
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Ethics approval
Ethics application status
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Summary
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.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT02725268
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Medical Director Clinical Science
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Address
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Millennium Pharmaceuticals, Inc.
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT02725268
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