Clinical Trial Results:
Progression-free Survival after Minimally Invasive Surgical Microwave Ablation (MIS-MWA) plus Durvalumab (MEDI4736) and Tremelimumab for Unresectable Non-metastatic Locally Advanced Pancreatic Cancer. MIMIPAC trial.
Summary
|
|
EudraCT number |
2018-002852-34 |
Trial protocol |
BE |
Global end of trial date |
29 Jan 2024
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
20 Sep 2024
|
First version publication date |
20 Sep 2024
|
Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
Trial identification
|
|||
Sponsor protocol code |
S61508
|
||
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT04156087 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
AstraZeneca identifier: AZ ESR-17-12926 | ||
Sponsors
|
|||
Sponsor organisation name |
UZLeuven
|
||
Sponsor organisation address |
Herestraat 49, Leuven, Belgium, 3000
|
||
Public contact |
Halit Topal, UZ Leuven, 0032 16346009 , halit.topal@uzleuven.be
|
||
Scientific contact |
Halit Topal, UZ Leuven, 0032 16346009 , halit.topal@uzleuven.be
|
||
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
29 May 2024
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
29 Jan 2024
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
29 Jan 2024
|
||
Was the trial ended prematurely? |
Yes
|
||
General information about the trial
|
|||
Main objective of the trial |
Median progression-free survival time was chosen as a clinically meaningful outcome. The study aimed to detect a 2-fold increase of median PFS time compared to the historical reference, i.e. from 6 to 12 months.
|
||
Protection of trial subjects |
Ethics review and approval, informed consent, prophylactic medication prior to infusions (to prevent chemotherapy known adverse events as per current practice and protocol recommendations), supportive care and routine monitoring.
|
||
Background therapy |
Systemic chemotherapy gemcitabine will be started 6 weeks after MIS-MWA. Gemcitabine will be given at a dose of 1000 mg /m², once a week for 3 weeks, followed with a week of rest. Patients will be treated with gemcitabine and durvalumab until disease progression is observed on CT-scan measurements. | ||
Evidence for comparator |
/ | ||
Actual start date of recruitment |
06 Jan 2020
|
||
Long term follow-up planned |
Yes
|
||
Long term follow-up rationale |
Safety, Efficacy | ||
Long term follow-up duration |
2 Years | ||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Belgium: 12
|
||
Worldwide total number of subjects |
12
|
||
EEA total number of subjects |
12
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
5
|
||
From 65 to 84 years |
7
|
||
85 years and over |
0
|
|
|||||||||||
Recruitment
|
|||||||||||
Recruitment details |
The first patient was included on 09-May-2020. Last patient last treatment visit was on 04-Aug-2024. Recruitment was stopped on 31-Oct-2022. 16 subjects have been screened; 4 were screening failures and 12 were enrolled and received at least one infusion of durvalumab and tremelimumab on study. Survival data cutoff date was 29/05/2024. | ||||||||||
Pre-assignment
|
|||||||||||
Screening details |
The study target population is represented by patients with unresectable non-metastatic locally advanced pancreatic cancer, histologically or cytologically confirmed, eligible for treatment with durvalumab, tremelimumab and gemcitabine in a first line setting and fit for MIS-MWA. | ||||||||||
Period 1
|
|||||||||||
Period 1 title |
Full duration = baseline to end of FU (overall period)
|
||||||||||
Is this the baseline period? |
Yes | ||||||||||
Allocation method |
Not applicable
|
||||||||||
Blinding used |
Not blinded | ||||||||||
Arms
|
|||||||||||
Arm title
|
MWA + D + T + Gemcitabine (SOC) | ||||||||||
Arm description |
Durvalumab and tremelimumab are the investigational drugs. Per protocol, patients receive durvalumab (MEDI4736) 1500 mg IV every four weeks in combination with tremelimumab 75 mg IV every four weeks, starting two weeks prior to MIS-MWA. Standard gemcitabine (1g/m²) is started 6 weeks after the MIS-MWA procedure and is given weekly, in four-week cycles, three administrations followed by a week of rest as background treatment. Gemcitabine is given in combination with both tremelimumab and durvalumab (MEDI4736) on weeks 6 and 10 after MIS-MWA and in combination with durvalumab only afterwards. While only four doses of tremelimumab are foreseen, treatment with durvalumab and gemcitabine is continued until disease progression is observed on CT-scan measurements or patient withdrawal for other reason. | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
Durvalumab
|
||||||||||
Investigational medicinal product code |
1428935-60-7
|
||||||||||
Other name |
Imfinzi, MEDI4736
|
||||||||||
Pharmaceutical forms |
Solution for injection/infusion
|
||||||||||
Routes of administration |
Intravenous use
|
||||||||||
Dosage and administration details |
All patients will receive durvalumab (1500mg Q4W) in combination with tremelimumab (75 mg IV Q4W) until confirmed disease progression unless there is unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met. Standard infusion time for each is 60 minutes (±5 minutes). Tremelimumab will be administered first; the durvalumab infusion will start approximately 1 hour (maximum 2 hours) after the end of the tremelimumab infusion.
|
||||||||||
Investigational medicinal product name |
Tremelimumab
|
||||||||||
Investigational medicinal product code |
745013-59-6
|
||||||||||
Other name |
MEDI1123
|
||||||||||
Pharmaceutical forms |
Solution for injection/infusion
|
||||||||||
Routes of administration |
Intravenous use
|
||||||||||
Dosage and administration details |
All patients will receive durvalumab (1500mg Q4W) in combination with tremelimumab (75 mg IV Q4W) until confirmed disease progression unless there is unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met. Standard infusion time for each is 60 minutes (±5 minutes). Tremelimumab will be administered first; the durvalumab infusion will start approximately 1 hour (maximum 2 hours) after the end of the tremelimumab infusion.
|
||||||||||
|
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Baseline characteristics reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Full duration = baseline to end of FU
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
All patients who consented to participate in the study and fulfilled all inclusion/exclusion criteria at baseline. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis sets
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set title |
Intent to treat set (ITT)
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set type |
Intention-to-treat | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
All patients who consented to participate in the study and fulfilled all inclusion/exclusion criteria at baseline.
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
End points reporting groups
|
|||
Reporting group title |
MWA + D + T + Gemcitabine (SOC)
|
||
Reporting group description |
Durvalumab and tremelimumab are the investigational drugs. Per protocol, patients receive durvalumab (MEDI4736) 1500 mg IV every four weeks in combination with tremelimumab 75 mg IV every four weeks, starting two weeks prior to MIS-MWA. Standard gemcitabine (1g/m²) is started 6 weeks after the MIS-MWA procedure and is given weekly, in four-week cycles, three administrations followed by a week of rest as background treatment. Gemcitabine is given in combination with both tremelimumab and durvalumab (MEDI4736) on weeks 6 and 10 after MIS-MWA and in combination with durvalumab only afterwards. While only four doses of tremelimumab are foreseen, treatment with durvalumab and gemcitabine is continued until disease progression is observed on CT-scan measurements or patient withdrawal for other reason. | ||
Subject analysis set title |
Intent to treat set (ITT)
|
||
Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
All patients who consented to participate in the study and fulfilled all inclusion/exclusion criteria at baseline.
|
|
|||||||||||||
End point title |
Progression free survival (PFS) [1] | ||||||||||||
End point description |
Standard Kaplan Meier analysis, performed with IBM SPSS statistics, version 29 0.2.0. Survival data cutoff date was 29/05/2024.
The study is exploratory and results are presented descriptively. No formal comparison was foreseen, this is a single arm study. The reference PFS time in patients with non-metastatic locally advanced pancreatic cancer treated with gemcitabine monotherapy is about 6 months.
No conclusion can be drawn due to the insufficient sample size.
|
||||||||||||
End point type |
Primary
|
||||||||||||
End point timeframe |
From signature of informed consent to disease progression or death from any cause.
|
||||||||||||
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: Standard Kaplan Meier analysis for PFS and OS, performed with IBM SPSS statistics, version 29 0.2.0. Survival data cutoff date was 29/05/2024.The study is exploratory and results are presented descriptively. No formal comparison was foreseen, this is a single arm study. The reference PFS time in patients with non-metastatic locally advanced pancreatic cancer treated with gemcitabine monotherapy is about 6 months.No conclusion can be drawn due to the insufficient sample size. |
|||||||||||||
|
|||||||||||||
Attachments |
Untitled (Filename: MIMIPAC_PFS_cutoff 240529_chart.jpg) |
||||||||||||
No statistical analyses for this end point |
|
||||||||||
End point title |
Safety | |||||||||
End point description |
Clinical and hematological toxicity (NCI CTCAE v. 5.0) of chemotherapy and immunotherapy. Summary tabulations and line listings of serious adverse events (14 SAE reported), non-serious adverse events, laboratory anomalies are attached. Also see section Adverse events.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
From signature of informed consent to 90 days post last immunotherapy dose.
|
|||||||||
|
||||||||||
Attachments |
Untitled (Filename: Safety A1_SAE LL.pdf) Untitled (Filename: Safety A2 SAE ST.pdf) Untitled (Filename: Safety A3 AE LL.pdf) Untitled (Filename: Safety A4 AE ST.pdf) Untitled (Filename: Safety A5 Lab ST.pdf) |
|||||||||
No statistical analyses for this end point |
|
||||||||||
End point title |
Post operative complications | |||||||||
End point description |
The number and type of postoperative complications were recorded, i.e. fistula, hemorrhage, abscess, etc... The therapy-oriented severity grading system (TOSGS) of complications were also used and complications were allocated to surgical (SSC) and non-surgical site (NSSC) complications.
Post operative complications after the MIS-MWA procedure occurred in one patient. Three occurrences were recorded as separate AEs and listed as SAE cases 9 and 10 with fatal outcome for this patient. See Safety and Adverse event sections.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
From signature of informed consent to 90 days post last immunotherapy dose.
|
|||||||||
|
||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Length of hospital stay | ||||||||||||
End point description |
Postoperative length of hospital stay (after MIS-MWA)
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From signature of informed consent to 90 days post last immunotherapy dose.
|
||||||||||||
|
|||||||||||||
No statistical analyses for this end point |
|
|||||||||||||
End point title |
Overall survival (OS) | ||||||||||||
End point description |
Tertiary endpoint. Standard Kaplan Meier analysis, performed with IBM SPSS statistics, version 29 0.2.0.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
From signature of informed consent to death of any cause or date of last contact for patients still alive.
|
||||||||||||
|
|||||||||||||
Attachments |
Untitled (Filename: MIMIPAC_OS_cutoff 240529_chart.jpg) |
||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
From signature of ICF to 90 days post last dose of immunotherapy (mandatory safety FU)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
Only grade 3/4/5 of non serious adverse events are reported. All events including grade 1/2 are available in line listings attached.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
NCI CTCAE | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
5
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Total (safety set)
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|
|||
Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
19 Mar 2020 |
Substantial amendment 1 – ICF V1.2 dd 19Feb2020 |
||
14 Jan 2021 |
Substantial amendment 2 – protocol V9 dd 10 Nov 2020 and ICF V1.3 dd 13 Jan 2021 |
||
24 Aug 2021 |
Substantial amendment 3 - protocol V10 dd 20 Jul 2021 and ICF V2 dd 20 Jul 2021 |
||
24 May 2023 |
Substantial amendment 4 - protocol V11 dd 17 Apr 2023 and ICF V3 dd 17 Apr 2023 |
||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
Insufficient sample size due to low accrual. Non randomised design for an efficacy endpoint | |||
Online references |
|||
http://www.ncbi.nlm.nih.gov/pubmed/25524417 http://www.ncbi.nlm.nih.gov/pubmed/24907635 http://www.ncbi.nlm.nih.gov/pubmed/22658128 http://www.ncbi.nlm.nih.gov/pubmed/24070507 http://www.ncbi.nlm.nih.gov/pubmed/15173017 http://www.ncbi.nlm.nih.gov/pubmed/32664183 http://www.ncbi.nlm.nih.gov/pubmed/31318392 http://www.ncbi.nlm.nih.gov/pubmed/31996388 http://www.ncbi.nlm.nih.gov/pubmed/33442411 http://www.ncbi.nlm.nih.gov/pubmed/30578687 http://www.ncbi.nlm.nih.gov/pubmed/32816849 http://www.ncbi.nlm.nih.gov/pubmed/31676670 |