Clinical Trial Results:
Open-label pilot Phase I / II study on hyperthermic intraperitoneal chemotherapy ( HIPEC ) after macroscopically complete resection ( R0 / R1 ) of adenocarcinomas of the pancreas ( PanHIPEC )
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Summary
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EudraCT number |
2015-002288-41 |
Trial protocol |
DE |
Global end of trial date |
31 Oct 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
07 Oct 2021
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First version publication date |
07 Oct 2021
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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 |
PanHIPEC
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT02863471 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
University hospital Tuebingen
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Sponsor organisation address |
Hoppe - Seyler - Straße 3, Tuebingen, Germany, 72076
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Public contact |
PI, Dr. med. P. Horvath, University Department of General, Visceral and Transplant Surgery Tübingen, +49 70712981222, Philip.Horvath@med.uni-tuebingen.de
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Scientific contact |
PI, Dr. med. P. Horvath, University Department of General, Visceral and Transplant Surgery Tübingen, +49 70712981222, Philip.Horvath@med.uni-tuebingen.de
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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 |
19 Mar 2019
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
31 Oct 2018
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Global end of trial reached? |
Yes
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Global end of trial date |
31 Oct 2018
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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 |
30 days mortality after macroscopically complete resection ( R0 / R1 ) of pancreatic adenocarcinoma in combination with HIPEC
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Protection of trial subjects |
The study was conducted in accordance with the Declaration of Helsinki and the ICH Guidelines in Good Clinical Practice. The study was not started before the competent ethics committee had given a favorable opinion. Written informed consent was obtained from all patients and the study was only conducted as approved by the Ethics committee and the competent authority.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
03 Dec 2015
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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 |
Germany: 32
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Worldwide total number of subjects |
32
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EEA total number of subjects |
32
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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) |
20
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From 65 to 84 years |
12
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85 years and over |
0
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Recruitment
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Recruitment details |
16 Patients were planned + recruited in the university hospital Tuebingen. Date of first patient enrollment: 03.12.2015. Date of last patient enrollment: 04.12.2017.End of study:31.10.2018. Explanation: The system contains an error in the calculation of patients. There was no comparison arm! This was a single-arm study with 16 recruited patients! | |||||||||
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Pre-assignment
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Screening details |
20 patients were assessed, 2 patients were excluded due to extended disease,2 patients were excluded from HIPEC during surgery, 1 patient due to histologically unconfirmed PDAC diagnosis,the other for severe hemorrhagic diathesis with edema of the gut. A total of 16 patients with confirmed PDAC diagnosis received HIPEC after oncological resection. | |||||||||
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Period 1
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Period 1 title |
Gemcitabin (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||
Roles blinded |
Investigator, Monitor, Subject, Carer, Assessor | |||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Gemcitabin | |||||||||
Arm description |
16 patients with confirmed PDAC diagnosis received HIPEC after oncological resection. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Gemcitabin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder for infusion
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Routes of administration |
Intraperitoneal use
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Dosage and administration details |
during surgery 100mg/m2 KOF, 60 minutes intraperitoneal, hypertherme lavage
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Arm title
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Gemcitabin | |||||||||
Arm description |
there was no comparison arm | |||||||||
Arm type |
No intervention | |||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Baseline characteristics reporting groups
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Reporting group title |
Gemcitabin
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Reporting group description |
16 patients with confirmed PDAC diagnosis received HIPEC after oncological resection. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Gemcitabin
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Reporting group description |
there was no comparison arm | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Baseline
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Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Sample Size Calculation: 30-day mortality rate was the primary end point for statistical analysis. A one-sided 95% exact confidence interval (CI) and a one-sided exact binomial test were used to evaluate the null hypothesis that the observed 30-day mortality rate is ≥10% versus the alternative that the 30-day mortality rate is <10%. Given a required number of 16 patients, the probability that a critical event (death within 30 days of surgery) will occur in at least one patient is 81.5% if the incidence of critical events is ≥10% in the general population. The exact one-sided binomial test was used for statistical analysis.End point assessment: The primary endpoint analyzed was the incidence of death within the mITT population (all included patients who actually underwent planned HIPEC in addition to oncologic pancreatic resection) (with 95% CI). In addition, survival probability for 30-day versus minimum acceptable probability of π 0 = 0.9 was compared by one-sided binomial test.
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End points reporting groups
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Reporting group title |
Gemcitabin
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Reporting group description |
16 patients with confirmed PDAC diagnosis received HIPEC after oncological resection. | ||
Reporting group title |
Gemcitabin
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Reporting group description |
there was no comparison arm | ||
Subject analysis set title |
Baseline
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Sample Size Calculation: 30-day mortality rate was the primary end point for statistical analysis. A one-sided 95% exact confidence interval (CI) and a one-sided exact binomial test were used to evaluate the null hypothesis that the observed 30-day mortality rate is ≥10% versus the alternative that the 30-day mortality rate is <10%. Given a required number of 16 patients, the probability that a critical event (death within 30 days of surgery) will occur in at least one patient is 81.5% if the incidence of critical events is ≥10% in the general population. The exact one-sided binomial test was used for statistical analysis.End point assessment: The primary endpoint analyzed was the incidence of death within the mITT population (all included patients who actually underwent planned HIPEC in addition to oncologic pancreatic resection) (with 95% CI). In addition, survival probability for 30-day versus minimum acceptable probability of π 0 = 0.9 was compared by one-sided binomial test.
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End point title |
Overall Survival | ||||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
30-day mortality after macroscopically complete resection of adenocarcinoma of the pancreas in combination with HIPEC.
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Statistical analysis title |
Primary statistical analysis | ||||||||||||||||
Statistical analysis description |
30d mortality rate = primary end point,a one-sided 95% exact CI and a one-sided exact binomial test were used to evaluate the null hypothesis that the observed 30-day mortality rate is ≥10% versus the alternative that the 30-day mortality rate is <10%. Given a required number of 16 patients, the probability that a critical event (death within 30 days of surgery) will occur in at least one patient is 81.5% if the incidence of critical events is ≥10% in the general population.
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Comparison groups |
Gemcitabin v Gemcitabin v Baseline
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Number of subjects included in analysis |
48
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Analysis specification |
Pre-specified
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Analysis type |
other [1] | ||||||||||||||||
P-value |
= 0.9 | ||||||||||||||||
Method |
Kaplan-Meyer, COX-Regression,Log-Rank | ||||||||||||||||
Confidence interval |
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95% | ||||||||||||||||
sides |
1-sided
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lower limit |
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upper limit |
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| Notes [1] - n.a there is no comparison group |
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Adverse events information [1]
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Timeframe for reporting adverse events |
Within 30 days after invention, no patient died or experienced ay adverse events higher than grade 3 that were related to HIPEC. Furthermore, treatment-related AEs were prospectively ducemnted and categorized as expected or unexpected.
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Assessment type |
Non-systematic | ||
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Dictionary used for adverse event reporting
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Dictionary name |
NCI CTCAE | ||
Dictionary version |
4.0
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| Frequency threshold for reporting non-serious adverse events: 0% | |||
| Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: Considering the results of this prospective phase I/II clinical trial a subsequent investigation of a potential clinical benefit (e.g., prolonged overall survival and progression-free survival) for patients with resectable pancreatic adenocarcinoma seems feasible and is also justifiable based on the results obtained, as the HIPEC procedure is not associated with a significant increase in short-term mortality and no signal of unexpected SAEs was evident in our study. |
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
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. | |||
| None reported | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/34131821 |
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