Clinical Trial Results:
Phase 2 study in pretreated patients with advanced pancreatic cancer to assess efficacy of ipilimumab, nivolumab and tocilizumab in combination with radiation.
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Summary
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EudraCT number |
2019-004438-40 |
Trial protocol |
DK |
Global end of trial date |
17 Nov 2021
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Results information
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Results version number |
v1(current) |
This version publication date |
25 Oct 2022
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First version publication date |
25 Oct 2022
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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 |
GI1950
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04258150 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Department of Oncology, Herlev & Gentofte Hospital
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Sponsor organisation address |
Borgmester Ib Juuls Vej 1, Herlev, Denmark, 2730
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Public contact |
PI Inna Chen, Department of Oncology, Herlev & Gentofte Hospital, +45 38682898, inna.chen@regionh.dk
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Scientific contact |
PI Inna Chen, Department of Oncology, Herlev & Gentofte Hospital, +45 38682898, inna.chen@regionh.dk
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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 |
07 Feb 2022
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
17 Nov 2021
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Global end of trial reached? |
Yes
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Global end of trial date |
17 Nov 2021
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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 |
For PART A LEAD IN : To assess the efficacy of ipilimumab, nivolumab and tocilizumab in combination with SBRT in terms of objective response rate (ORR).
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Protection of trial subjects |
Patients that signed informed consent and fulfilling eligibility criteria were included. Continued monitoring of standard safety parameters during treatment.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
17 Apr 2020
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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 |
Denmark: 26
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Worldwide total number of subjects |
26
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EEA total number of subjects |
26
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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) |
15
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From 65 to 84 years |
11
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85 years and over |
0
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Recruitment
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Recruitment details |
The trial was opened for recruitment in april 2020 and closed for enrollment in January 2021 . Patients were included at a single site, Herlev Hospital, Denmark. | ||||||||||
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Pre-assignment
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Screening details |
Eligible patients were ≥ 18 years with locally advanced or metastatic pancreatic cancer, who had progressed during or after at least 1 line of chemotherapy in the advanced setting, ECOG PS 0-1, adequate organ and hematologic functions. Key exclusion criteria were active autoimmune disease and requirement for > 10 mg/d of prednisone or equivalent. | ||||||||||
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Period 1
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Period 1 title |
Protocol Treatment (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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Ipilimumab, nivolumab, tocilizumab, and SBRT 15 Gy | ||||||||||
Arm description |
Patients received SBRT of 15 Gy to a single primary or metastatic lesion administered on day 1 of the first cycle. Ipilimumab (1 mg/kg) was administered intravenously on day 1 and repeated once after 6 weeks. Nivolumab (6 mg/kg) and tocilizumab (8 mg/kg) were given intravenously on day 1 and every 4 weeks for up to one year or until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or clear clinical deterioration according to the investigator’s judgment. | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
Tocilizumab
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Tocilizumab 8 mg/kg was given IV on day 1 (± 3 days) over 1-hour, repeated every 4 weeks, for up to one year or until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or clear clinical deterioration according to the investigator’s judgment.
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Investigational medicinal product name |
Nivolumab
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Nivolumab 6 mg/kg (up to 480 mg maximum) was given IV on day 1 (± 3 days) of each 28-day treatment cycle until the progression of disease or maximum of 48 weeks, discontinuation due to toxicity, withdrawal of consent.
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Investigational medicinal product name |
Ipilimumab
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Concentrate for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Ipilimumab (1 mg/kg) was administered intravenously on day 1 and repeated once after 6 weeks.
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Baseline characteristics reporting groups
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Reporting group title |
Protocol Treatment
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Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Ipilimumab, nivolumab, tocilizumab, and SBRT 15 Gy
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Reporting group description |
Patients received SBRT of 15 Gy to a single primary or metastatic lesion administered on day 1 of the first cycle. Ipilimumab (1 mg/kg) was administered intravenously on day 1 and repeated once after 6 weeks. Nivolumab (6 mg/kg) and tocilizumab (8 mg/kg) were given intravenously on day 1 and every 4 weeks for up to one year or until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or clear clinical deterioration according to the investigator’s judgment. | ||
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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 |
Tumor assessments were done every 8 weeks until progression of disease
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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, not to be compared with historical data. |
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| Notes [2] - 3 patients without post-baseline imaging for tumorassessment |
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| No statistical analyses for this end point | |||||||||
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End point title |
Disease control rate | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Tumor assessements were performed every 8 weeks until progression
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| Notes [3] - 3 patients without post-baseline imaging available for tumor assessment |
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| No statistical analyses for this end point | |||||||||
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End point title |
Best overall response | ||||||||||||||||
End point description |
Best overall response according to RECIST 1.1
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End point type |
Secondary
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End point timeframe |
Tumor assessment was performed every 8 weeks until progression of disease
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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 |
AE were collected from initiation of study treatment until 100 days after discontinuation of dosing or until starting a new anti-neoplastic therapy (whichever occured first)
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Adverse event reporting additional description |
All serious AE are reported. Non serious adverse event are reported if events were assessed with causal relationship to study treatment only.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
NCI-CTCAE | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
5
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Reporting groups
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Reporting group title |
Ipilimumab, nivolumab, tocilizumab, and SBRT 15 Gy
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Reporting group description |
Patients received SBRT of 15 Gy to a single primary or metastatic lesion administered on day 1 of the first cycle. Ipilimumab (1 mg/kg) was administered intravenously on day 1 and repeated once after 6 weeks. Nivolumab (6 mg/kg) and tocilizumab (8 mg/kg) were given intravenously on day 1 and every 4 weeks for up to one year or until confirmed disease progression, unacceptable toxicity, withdrawal of consent, or clear clinical deterioration according to the investigator’s judgment. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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 Jul 2020 |
- Number of biopsies per timepoint increased to up to three biopsies for additional translational analyses |
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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. | |||
| The study was prematurely ended as the predictive probarbility to meet efficacy gate (ORR 15%) was not given. A substantiel amendment was pre-planned to expand as either non-RCT or RCT depending on ORR observed in part A. | |||
