Clinical Trial Results:
Phase II study of oral PHA-848125AC in patients with malignant thymoma previously treated with multiple lines of chemotherapy
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Summary
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EudraCT number |
2013-000344-25 |
Trial protocol |
IT |
Global end of trial date |
17 Dec 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
27 Nov 2019
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First version publication date |
27 Nov 2019
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Other versions |
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Summary report(s) |
Synopsis |
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 |
CDKO-125a-007
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01301391 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
TIZIANA LIFE SCIENCES PLC
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Sponsor organisation address |
3rd floor, 11-12St. James's Square, LONDON, United Kingdom, SW1Y 4LB
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Public contact |
Vaseem Palejwala, TIZIANA LIFE SCIENCES PLC, +1 267 982 Ext. 9784, vpalejwala@tizianalifesciences.com
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Scientific contact |
Cristina Davite, CLinical Organization for Strategies & Solutions S.r.l. - CLIOSS S.r.l., +39 03311482, cristina.davite@clioss.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 |
27 Nov 2017
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
31 May 2017
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Global end of trial reached? |
Yes
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Global end of trial date |
17 Dec 2018
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
Assessment of the antitumor activity of PHA-848125AC in patients with recurrent or metastatic, unresectable B3 thymoma or thymic carcinoma who have received more than one line of prior systemic therapy for advanced / metastatic disease. Antitumor activity will be evaluated on the basis of the progression-free survival status at 3 months.
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Protection of trial subjects |
Study protocol foresees that therapies considered necessary for the patient's well being might be given at the discretion of the Investigator, i.e., chronic treatments for concomitant medical conditions, as well as agents required for life-threatening medical problems.
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Background therapy |
None. | ||
Evidence for comparator |
Not applicable. | ||
Actual start date of recruitment |
02 Feb 2011
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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 |
Italy: 15
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Country: Number of subjects enrolled |
United States: 15
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Worldwide total number of subjects |
30
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EEA total number of subjects |
15
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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) |
23
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From 65 to 84 years |
7
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85 years and over |
0
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Recruitment
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Recruitment details |
Thirty-four patients were recruited from 02 February 2011 to 28 January 2016. | ||||||||||||||||||||
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Pre-assignment
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Screening details |
Thirty patients were enrolled and treated with milciclib. Overall four patients were screening failure, due to inclusion /exclusion criteria not sactisfied (one patient) or other reasons (3 patients). | ||||||||||||||||||||
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Period 1
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Period 1 title |
Overall Trial ( overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||||||||||||
Blinding implementation details |
Not applicable.
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Arms
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Arm title
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Arm 1 | ||||||||||||||||||||
Arm description |
All patients treated with milciclib. | ||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||
Investigational medicinal product name |
Milciclib maleate
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Investigational medicinal product code |
PHA-848125AC
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Other name |
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Pharmaceutical forms |
Capsule, hard
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Routes of administration |
Oral use
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Dosage and administration details |
Milciclib maleate was to be administered at the flat dose of 150 mg/day once daily for 7 consecutive days of each treatment cycle. Therefore, a treatment cycle included 7 days of milciclib administration (Days 1 to 7) followed by 7 days of rest (Days 8 to 14) for a total of a 14 days period (2-week cycle).
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Baseline characteristics reporting groups
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Reporting group title |
Arm 1
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Reporting group description |
All patients treated with milciclib. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Arm 1
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Reporting group description |
All patients treated with milciclib. | ||
Subject analysis set title |
Evaluable patients
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
the patient population for the primary efficacy analysis of PFS-3 rate consisted of all treated patients who had fulfilled the following additional conditions:
- They had received at least 80% of drug in the first two cycles overall.
- They had undergone baseline and >/=1 on-treatment tumor/oncologic assessments or had died before tumor re-assessment.
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End point title |
Progression-free survival rate at 3 months (PFS-3 rate) [1] | ||||||||
End point description |
The PFS-3 rate was calculated as the proportion of evaluable patients known to be alive and progression-free at ≥ 3 months since study treatment start, out of the total number of evaluable patients.
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End point type |
Primary
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End point timeframe |
From baseline to 3 months after the patient started the study treatment
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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: A PFS-3 rate of at least 25% was obtained, as expected. The p-value given by the exact binomial test (<.001) lead the rejection of the null hyphotesis (p=0.25) in favour of the althernative one (p=0.50). |
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| No statistical analyses for this end point | |||||||||
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End point title |
Objective Response Rate (CR+PR) | ||||||||
End point description |
Confirmed Objective Response Rate (CR + PR) according to RECIST guideline (version 1.1).
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End point type |
Secondary
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End point timeframe |
During all study period
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| No statistical analyses for this end point | |||||||||
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End point title |
Progression-free survival | ||||||||
End point description |
The time from the date of treatment start to the date of first documentation of objective progression or of death due to any cause, whichever came first.
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End point type |
Secondary
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End point timeframe |
During all study period
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| No statistical analyses for this end point | |||||||||
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End point title |
Duration of response | ||||||||
End point description |
Duration of response was defined, for the subset of patients with CR or PR, as the time for when criteria for response were met until first date that recurrent or progressive disease had been objectively documented (taking as reference for progressive disease the smallest measurements recorded on study).
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End point type |
Secondary
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End point timeframe |
During all study period
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| No statistical analyses for this end point | |||||||||
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End point title |
Overall Survival at 21 months | ||||||||
End point description |
During all study period
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End point type |
Secondary
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End point timeframe |
Overall survival was defined as the time from the date of treatment start to the date of death from any causes.
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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 |
During all study period and followed until 28 days after the last dose administration of investigational product.
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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 |
20.1
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Reporting groups
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Reporting group title |
Arm1
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Reporting group description |
All patients treated with milciclib | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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13 Sep 2011 |
- To change Inclusion Criterion # 10, by adding creatinine clearance (CrCl) as a parameter to evaluate patients' renal function at study entry,
- To better specify time window for oncologic assessment,
- To add the possibility to investigate the baseline status of additional biomarkers
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13 Dec 2011 |
- To add the recommendation to monitor patients for events indicative of, or suggestive of, TMA/HUS (Thrombotic Microangiopathy/Hemolytic Uremic Syndrome) and in case of such events to temporarily hold study drug administration and to perform specific analyses to determine whether the events are compatible with TMA/HUS.
- To add information related to a new IMP (Investigational Medicinal Product) packaging and labeling.
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30 Jul 2012 |
- To reduce the frequency of ocular examination. The amended ophthalmologic schedule was as follows: at baseline and at 1, 2, 3, 4.5, 7.5 months, and then after every three months until the end of last treatment cycle.
- To reduce the frequency of visits at the site for patients who had already received 6 treatment cycles and remain on treatment for a longer period of time (more than 6 cycles).
- To update the shelf life of the 50 mg and 100 mg capsules and to delete the 10 mg capsules since not used in the current study. In addition, the original formulation has been completed used and therefore it has been deleted.
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24 Jan 2013 |
- To notify that the study, so far monocentric, changed into a multicenter phase II clinical study. Considering the rarity of the disease, it was decided to extend the number of the investigational sites to increase the accrual rate of patients.
- To notify that the histological diagnosis of thymic carcinoma, when made by another institution, had to be confirmed by pathologist of the investigational site to whom the patient is addressed.
- To delete the sentence related to the duration of accrual. In fact, due to the slow accrual rate, the NCI prevision to enroll 10-12 patients per year and to conclude the study within 2-3 years was not going to be satisfied.
- To allow for the evaluation of additional biomarkers to the ones already foreseen by the original protocol on tumor biopsies collected at baseline and to inform that the analysis will be performed in consenting patients in designated facilities in NMS and/or NIH/NCI. The baseline status of these additional markers under validation and related to the mechanism of action of milciclib will be investigated for any possible correlation with treatment efficacy. The additional analyses will not imply collection of additional tumor biopsies from patients.
- To report an administrative notification: from 01 November 2012, Nerviano Medical Sciences (NMS) had transferred its clinical development department to Clinical Organization for Strategies and Solutions (CLIOSS S. r. L). Therefore, all clinical and pharmacovigilance activities resulted delegated to CLIOSS S. r. L.
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09 Mar 2017 |
- To notify study discontinuation. Enrollment was completed on January 2016 and since sufficient data were already collected and the primary efficacy endpoint of the study was already achieved (i.e., the progression free survival status at 3 months was obtained in 13 out of the 24 evaluable patients (54.2%) i.e., more than the 12 successes required by protocol), a data cut-off on 31 May 2017 was planned, in order to proceed with clinical database closure and the preparation of the Clinical Study Report. The Sponsor continued to guarantee the supply of the investigational compound until the patients still on treatment would have benefit from the therapy. After the cut-off date, all the assessments data pertaining to the patients still on treatment were no longer collected in the Case Report Form, but only in the patient’s medical notes. Safety was to be followed up for Serious Adverse Events only: SAEs were to be notified to CLIOSS Pharmacovigilance up to 28 days after the last patient had taken his/her milciclib maleate last dose. The intention with this data cut-off of 31 May 2017 was to bring the study schedule more closely aligned to standard clinical practice.
- End of study definition. End of study can only occur when the last patient had discontinued study therapy and follow up period would have no longer been performed.
- Administrative changes: Tiziana Life Sciences PLC entered as new Sponsor for CDKO-125a-007 trial. With this amendment the name of Nerviano Medical Sciences (NMS) has been replaced with Tiziana Life Sciences, PLC (Tiziana) throughout the whole documents.
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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. | |||
| NA | |||
