Clinical Trial Results:
A Phase II Pilot Trial Of Paclitaxel Protein Bound Plus Cisplatin Plus Gemcitabine and the Addition Of Paricalcitol Upon Disease Progression in Patients With Previously Untreated Metastatic Pancreatic Ductal Adenocarcinoma
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Summary
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EudraCT number |
2017-004467-13 |
Trial protocol |
GB |
Global end of trial date |
19 Sep 2023
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Results information
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Results version number |
v1(current) |
This version publication date |
02 May 2025
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First version publication date |
02 May 2025
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Other versions |
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Summary report(s) |
Abstract CT214: Proceedings of the American Association for Cancer Research Annual Meeting 2024 |
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 |
012255
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04054362 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Barts Health NHS Trust
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Sponsor organisation address |
Joint Research and Management Office, 5 Walden Street, London, United Kingdom, E1 2EF
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Public contact |
Dr David Propper, Barts Health NHS Trust, 44 2034655051, bci-pinball@qmul.ac.uk
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Scientific contact |
Dr David Propper, Barts Health NHS Trust, 44 2034655051, bci-pinball@qmul.ac.uk
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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 Sep 2022
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
30 Sep 2022
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Global end of trial reached? |
Yes
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Global end of trial date |
19 Sep 2023
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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 determine the clinical benefit of adding paricalcitol to the regimen of paclitaxel protein bound plus cisplatin plus gemcitabine for patients with progressive metastatic pancreatic ductal adenocarcinoma.
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Protection of trial subjects |
Pancreatic cancer patients require new treatments that are better tolerated and with fewer associated toxicities. This combination has demonstrated anti-tumour activity previously.
The sequence of drug administration for patients receiving the standard two drug combination was paclitaxel protein bound followed by gemcitabine. For patients receiving the triple regimen, paclitaxel protein bound was given first, then after adequate hydration, cisplatin was given. Gemcitabine was given last because paclitaxel protein bound decreases cytidine deaminase which potentiates gemcitabine activity (less degradation of gemcitabine by the enzyme). When paricalcitol was added to the regimens it was e given last as in previously published studies (NCT02930902, NCT02754726).
Patients were treated with the two or three drug chemotherapy combination alone until upon reassessment they have stable or progressive disease. It was a decision by the Principal Investigator (PI) which of the two chemotherapy regimens were given. At this point the participants were given Paricalcitol with a paired biopsy.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
02 Apr 2018
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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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 |
United Kingdom: 13
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Worldwide total number of subjects |
13
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EEA total number of subjects |
0
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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) |
13
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
A total of 26 participants were enrolled at Barts Health NHS Trust in the UK. Of these, 13 participants started paricalcitol, therefore making them evaluable. The following analyses are limited to these 13 participants. | ||||||
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Pre-assignment
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Screening details |
- | ||||||
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Pre-assignment period milestones
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Number of subjects started |
13 | ||||||
Intermediate milestone: Number of subjects |
Started Paricalcitol: 13
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Number of subjects completed |
13 | ||||||
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Period 1
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Period 1 title |
Paricalcitol (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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Paricalcitol addition to chemotherapy | ||||||
Arm description |
Evalulable patients were patients that met the eligibility criteria and have received at least 1 dose of paricalcitol. | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Paricalcitol
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Solution for injection
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Dosage and administration details |
Fixed dose of 25 mcg over 5 minutes as slow push
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Baseline characteristics reporting groups
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Reporting group title |
Paricalcitol
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Paricalcitol addition to chemotherapy
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Reporting group description |
Evalulable patients were patients that met the eligibility criteria and have received at least 1 dose of paricalcitol. | ||
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End point title |
Objective Response Rate [1] | ||||||
End point description |
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End point type |
Primary
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End point timeframe |
Objective response rate after addition of paricalcitol
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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: Single arm study result. Of 12 evaluable participants, 5 (41.7%) achieved ORR (15.2–72.3%). No p-value or CI available for this result. |
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| No statistical analyses for this end point | |||||||
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End point title |
Disease control rate [2] | ||||||
End point description |
Of 11 participants evaluable at 9 weeks, 2 (18.2%) achieved DCR (2.3–51.8%).
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End point type |
Primary
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End point timeframe |
From starting paricalcitol to 9 weeks.
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| Notes [2] - 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: Single arm study result. Of 11 participants evaluable at 9 weeks, 10 (90.9%) achieved DCR (58.7–99.8%). |
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| Notes [3] - 2 patients did not have post paricalcitol scans. |
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| No statistical analyses for this end point | |||||||
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End point title |
Time to disease progression after paricalcitol [4] | ||||||||
End point description |
PFS is defined as the interval from the date of the addition of paricalcitol to the earliest date of documented evidence of recurrent or progressive disease, or the date of death due to any cause, whichever occurs.
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End point type |
Primary
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End point timeframe |
Time from starting paricalcitol to disease progression
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| Notes [4] - 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: Single arm study result. 13 participants had disease progression or died after starting paricalcitol. Median (95% CI) time from starting paricalcitol to progression was 1.6 (1.1—2.4) months. |
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End point title |
Overall Survival [5] | ||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Overall survival was measured from the addition of paricalcitol to the date of death due to any cause, or the date of last contact (censored observations).
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| Notes [5] - 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: Single arm study result. 13 patients died after starting paricalcitol. Median (95% CI) time from starting paricalcitol to death was 4.6 (2.2—10.4) months. |
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Adverse events information
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Timeframe for reporting adverse events |
From informed consent until safety visit post treatment.
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Adverse event reporting additional description |
Only AE's during paricalcitol treatment reported here.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
CTCAE | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
4.03
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Reporting groups
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Reporting group title |
Paricalcitol addition to chemotherapy
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Reporting group description |
Evalulable patients were patients that met the eligibility criteria and have received at least 1 dose of paricalcitol. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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 Aug 2019 |
Change in treatment options, change in CI & Barts PI, administrative changes throughout protocol and PIS. Updated docs included: protocol, PIS, GP letter, patient card |
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28 May 2020 |
Change in treatment, to allow patients to enter directly into the study at the add on paricalcitol stage. Updated docs: Protocol and PIS.
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16 Mar 2021 |
Updated SmPC’s (all four updated). PIS’ updated to incorporate RSI updates.
Updates to the inclusion/exclusion criteria (Cr cl range updated and history of hearing impairment for those without cisplatin).
Minor administrative changes to the PIS and protocol. Extend end of study to 30Sep22.
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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. | |||
| Monitoring activities were severely limited during the COVID-19 pandemic, and an extension to data cleaning was requested following the end of trial date of 30th September 2022, to 12th May 2023. | |||
