Clinical Trial Results:
Safety and efficacy of the addition of IMM-101 Heat-Killed Whole Cell Mycobacterium obuense to standard stereotactic radiotherapy in locally advanced pancreatic cancer patients (LAPC-2 trial).
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Summary
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EudraCT number |
2019-000216-29 |
Trial protocol |
NL |
Global end of trial date |
21 Sep 2021
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Results information
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Results version number |
v1(current) |
This version publication date |
12 Jul 2024
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First version publication date |
12 Jul 2024
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Other versions |
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Summary report(s) |
Manuscript 2 Manuscript 1 |
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 |
NL68762.078.19
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Additional study identifiers
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ISRCTN number |
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US NCT number |
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WHO universal trial number (UTN) |
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Other trial identifiers |
NTR: NL7578 | ||
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Sponsors
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Sponsor organisation name |
Erasmus MC Cancer Institute
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Sponsor organisation address |
Doctor Molewaterplein 40, Rotterdam, Netherlands,
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Public contact |
Research coordinator, Erasmus MC, 0031 650032401, f.vantland@erasmusmc.nl
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Scientific contact |
Research coordinator, Erasmus MC, 0631949794 650032401, f.vantland@erasmusmc.nl
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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 |
29 Sep 2022
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
21 Sep 2021
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Global end of trial reached? |
Yes
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Global end of trial date |
21 Sep 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 |
This phase I/II study consists of 2 subsequent study parts. In the phase I part we will investigate the safety of combining IMM-101 administration with SBRT in 20 patients with locally advanced pancreatic cancer who have completed at least 4 cycles of FOLFIRINOX chemotherapy. If deemed safe and feasible (defined as max 6 out of 20 patients experiencing a grade 4/5 toxicity related to the IMM-101 intervention) we will continue inclusion in phase II with an additional 18 patients in order to be able to study efficacy of combining IMM-101 treatment with SBRT based on a 20% improvement of 1-year disease free survival.
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Protection of trial subjects |
The sponsor and the trial management team will guide conduct of the trial according
to Good Clinical Practice (GCP). The Principal Investigator will be responsible for the
conduct within his site.
Data will be handled confidentially. Each patient will receive an anonymous
identification code. To trace data back to an individual patient, a subject identification
code list will be used. The PI will safeguard the key to this code for patients included
at the site. The handling of personal data will comply with the Dutch Personal Data
Protection Act (in Dutch: Algemene verordening gegevensbescherming (AVG)). Data
will be kept as long as 15 years, according to the guidelines for Clinical Trials.
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Background therapy |
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Evidence for comparator |
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Actual start date of recruitment |
01 Jun 2019
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Efficacy | ||
Long term follow-up duration |
5 Years | ||
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 |
Netherlands: 38
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Worldwide total number of subjects |
38
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EEA total number of subjects |
38
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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) |
21
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From 65 to 84 years |
17
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85 years and over |
0
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Recruitment
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Recruitment details |
Patients with locally advanced pancreatic cancer who had been treated with at least four cycles of (m)FOLFIRINOX and who did not show progression of disease were screened for participation in the study. Patients were classified as LAPC according to the dutch resectability guidelines defined by the DPCG. | ||||||
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Pre-assignment
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Screening details |
Patients with LAPC, following systemic chemotherapy No progression of disease Inclusion and exclusion criteria are shown in the online publication | ||||||
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Period 1
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Period 1 title |
Complete trial (overall period)
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Is this the baseline period? |
Yes | ||||||
Allocation method |
Non-randomised - controlled
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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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Study treatment | ||||||
Arm description |
6 vaccinations of 1mg of intradermal IMM-101 over a period of three months (experimental) combined with 40 Gy of stereotactic radiotherapy (5 times 8 Gy) (standard of care) | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
IMM-101
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate for solution for injection
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Routes of administration |
Intradermal use
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Dosage and administration details |
1mg IMM-101, intradermal injection
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Baseline characteristics reporting groups
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Reporting group title |
Complete trial
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
overall cohort
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Subject analysis set type |
Full analysis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
not applicable
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End points reporting groups
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Reporting group title |
Study treatment
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Reporting group description |
6 vaccinations of 1mg of intradermal IMM-101 over a period of three months (experimental) combined with 40 Gy of stereotactic radiotherapy (5 times 8 Gy) (standard of care) | ||
Subject analysis set title |
overall cohort
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
not applicable
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End point title |
Adverse events [1] | ||||||||||||||||||||||||||||||||||||
End point description |
All grade 4 or 5 adverse events that were possibly, probably or likely related to the study treatment were regarded as events for the endpoint. Adverse events were scored according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The relationship between the treatment and the adverse events were judged by the study team. The manuscript can be found online which describes this in detail.
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End point type |
Primary
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End point timeframe |
during the complete 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: The previously observed grade 4 toxicity rate related to SBRT in the setting of LAPC was 10%. With a sample size of 20 patients (phase I) we were able to estimate a toxicity rate of 10% within a 95% confidence interval of [1.2%, 31.7%] using binomial exact method. This meant that at most 6/20 patients were allowed to have a grade 4 toxicity in the phase I trial before moving to the phase II. |
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Attachments |
Grade 3 or higher adverse events |
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||||||||
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End point title |
One-year PFS rate [2] | |||||||||
End point description |
The calculated one-year progression free survival rate was 47%.
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End point type |
Primary
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End point timeframe |
overall study period
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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: With previous data using SBRT, the one-year PFS rate was 45%. We hypothesized that by adding IMM-101 to SBRT, this could be improved to 65%. If the one-year PFS rate was < 65%, we would not proceed with a phase-III trial. To test this hypothesis we needed 38 patients (calculated with Fleming's test). Eventually, the one-year PFS rate was calculated in the cohort to analyze the primary end point. |
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Attachments |
OS and PFS |
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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 |
complete study period
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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 |
5.0
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Reporting groups
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Reporting group title |
Overall cohort
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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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22 May 2020 |
The possibility of offering maintenance vaccinations was added to the protocol:
If the standard of care CT scan at week 14 shows no signs of progression and the patient did not experience a SAE related to the 6 IMM101 vaccinations the patient is eligible for IMM-101 maintenance therapy for at most 12 months. The maintenance therapy will consist of a 0.05 ml dosage of IMM-101 with a 4 week interval until patients show clinical progression or withdraw from the study |
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21 Jul 2020 |
The protocol was ammended in order to make it possible to proceed to including more than 20 patients earlier.:
Safety will be assessed when the first 20 patients have received at least 3 vaccinations (i.e. 2 weeks prior to SBRT, day 1 of SBRT and 2 weeks after SBRT).
Before, the 20 patients needed to receive all the vaccinations (6 vaccinations) before we would be able to include more than 20 patients. |
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27 Nov 2020 |
Patients who dropped out before starting study treatment could be replaced: Patients who drop out of the study before receiving SBRT will be replaced by a new patient. The one-year PFS of 45% in the historical LAPC-1 cohort was calculated using data from only those patients who had received SBRT. To be able to perform the most accurate analysis for the PFS endpoint we can only analyze those patients who actually received SBRT.
We made an amendment to make in possible to analyze samples outside the EU: Translational analysis can be performed at third parties within and outside of the European Union. In this case the Sponsor will draw up an agreement with these Parties ensuring that data and/or samples are handled according to EU legislation. Only pseudonimized data and/or samples will be shared. Data will be transferred using a secured connection. |
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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. | |||
| None reported | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/36813171 http://www.ncbi.nlm.nih.gov/pubmed/36358718 |
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