Clinical Trial Results:
Phase II Study of Paclitaxel and TAK-228 in metastatic urothelial carcinoma (UC) and the impact of PI3K-mTOR pathway genomic alterations
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Summary
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EudraCT number |
2017-004486-27 |
Trial protocol |
ES |
Global end of trial date |
15 Apr 2021
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Results information
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Results version number |
v1(current) |
This version publication date |
06 Apr 2022
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First version publication date |
06 Apr 2022
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
X31005
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03745911 | ||
WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
Associació Per a la Recerca Oncològica (APRO)
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Sponsor organisation address |
Calle Vilarrúbias, 20 , SABADELL / Barcelona, Spain, 08202
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Public contact |
Joaquim Bellmunt, Associació Per a la Recerca Oncològica (APRO), 00 3493 227 47 60, oncologia.apro@gmail.com
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Scientific contact |
Joaquim Bellmunt, Associació Per a la Recerca Oncològica (APRO), 00 3493 227 47 60, oncologia.apro@gmail.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
30 Nov 2021
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
15 Apr 2021
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To evaluate the efficacy of TAK-228 (orally administered 3 days each week) in combination with weekly IV paclitaxel as assessed by objective response rate in patients with metastatic, previously treated urothelial carcinoma (UC).
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Protection of trial subjects |
The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
04 May 2018
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Spain: 22
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Worldwide total number of subjects |
22
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EEA total number of subjects |
22
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
12
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From 65 to 84 years |
10
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85 years and over |
0
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Recruitment
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Recruitment details |
Twenty eight patients were recruited, 6 of whom were considered screening failures (noncompliance with selection criteria). Therefore, 22 patients composed the modified intended to treat (mITT) population in this study conducted in 5 Spanish hospitals. | ||||||||||
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Pre-assignment
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Screening details |
Patients must have a diagnosis of metastatic or advanced histologically confirmed urothelial cancer (UC), having received prior systemic chemotherapy treatment for UC, with no limit for number of prior systemic chemotherapeutic or investigational treatment regimens. | ||||||||||
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Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||
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Arms
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Arm title
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TAK-228 and paclitaxel | ||||||||||
Arm description |
All patients included in the clinical trial received the combination of TAK-228 (orally) and Paclitaxel (IV infusion) regimen in 28-day cycles. Treatment was given until disease progression, unacceptable toxicity or patient withdrawal. | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
TAK-228
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
TAK-228 was administered orally at a dose of 4 mg once daily, 3 days per week (on Days 2-4, 9-11, 16-18, and 23-25 of a 28-day cycle) of a 28-day treatment cycle.
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Investigational medicinal product name |
Paclitaxel
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Paclitaxel was administered at a dose of 80mg/m2 IV infusion over 60 minutes once weekly for 3 consecutive weeks (on Days 1, 8, and 15 of a 28-day treatment cycle).
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Baseline characteristics reporting groups
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Reporting group title |
Overall Study
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Reporting group description |
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End points reporting groups
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Reporting group title |
TAK-228 and paclitaxel
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Reporting group description |
All patients included in the clinical trial received the combination of TAK-228 (orally) and Paclitaxel (IV infusion) regimen in 28-day cycles. Treatment was given until disease progression, unacceptable toxicity or patient withdrawal. | ||
Subject analysis set title |
mITT
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Subject analysis set type |
Modified intention-to-treat | ||
Subject analysis set description |
Modified intention-to-treat (mITT) population: included all randomized patients who received at least one dose of study treatment (N=22).
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End point title |
Overall Response Rate (ORR) [1] | ||||||||
End point description |
Percentage of patients with either a complete response (CR) or a partial response (PR) according to RECIST criteria (version 1.1).
The response rate (RR) is the proportion of all patients with confirmed PR or CR according to RECIST v1.1 from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The patient’s best overall response assignment will depend on the achievement of both measurement and confirmation criteria. A CR or PR is confirmed if a subsequent assessment (no less than 4 weeks after the initial response is noted) indicates no additional disease or growth of disease relative to the prior assessment. An assessment of SD does not require confirmation. If there are no post-baseline scans available for a patient, then the best response will be not available (NA).
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End point type |
Primary
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End point timeframe |
From the start of the treatment until disease progression/recurrence.
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No statistical analysis was planned for this end point. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Overall Survival (OS) | ||||||||
End point description |
Overall Survival (OS), defined as the time from randomization date until the date of death, regardless of the cause of death.
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End point type |
Secondary
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End point timeframe |
From randomization date to death from any cause.
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| No statistical analyses for this end point | |||||||||
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End point title |
Progression-free survival (PFS) | ||||||||
End point description |
Progression-free survival (PFS), defined as the time from randomization date until the first (radiologically) documented progression of disease or death from any cause, whichever occurred first.
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End point type |
Secondary
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End point timeframe |
From randomization to disease progression or death from any cause.
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
AEs received from the first day of the first cycle through 30 days after the last dose.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
v22.0
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Reporting groups
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Reporting group title |
Adverse events
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Reporting group description |
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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18 Apr 2018 |
Amendment 1: Changes in frequency of study schedule assessments after baseline visits. Modification of the Patient Information Sheet (PIS) to adapt it to the new schedule of assessments. Added definition of TIA (transient ischemic attack), on page 10. Description of an interim analysis (page 70), which will be carried out after the inclusion of the first 17 patients. Clarification on the duration of treatment and the possibility of maintaining TAK-228 when paclitaxel is suspended due to toxicity. Modification of the frequency of carrying out the TCs to adjust it to a temporary term instead of a determined number of cycles. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| The study could not demonstrate the primary endpoint (ORR) due to insufficient number of patients finally enrolled. | |||
