Clinical Trial Results:
A Phase 1/2 Study to Evaluate the Safety, Tolerability, Immune Response, and Clinical Efficacy of Cancer Peptide Vaccine S-488210 in Patients with Unresectable Locoregionally Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC)
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Summary
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EudraCT number |
2011-005014-12 |
Trial protocol |
BE DE |
Global end of trial date |
15 Jul 2014
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Results information
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Results version number |
v2(current) |
This version publication date |
09 Jul 2016
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First version publication date |
01 Aug 2015
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Other versions |
v1 |
Version creation reason |
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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 |
1122P1811
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Shionogi & Co., Ltd.
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Sponsor organisation address |
1-8 Doshomachi 3-chome Chuo-ku, Osaka/Osaka, Japan, 541-0045
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Public contact |
Kenji Igarashi, Shionogi & Co., Ltd., +81 664855082, kenji.igarashi@shionogi.co.jp
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Scientific contact |
Kenji Igarashi, Shionogi & Co., Ltd., +81 664855082, kenji.igarashi@shionogi.co.jp
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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 Jan 2015
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
15 Jul 2014
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Global end of trial reached? |
Yes
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Global end of trial date |
15 Jul 2014
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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 evaluate the safety and tolerability of S-488210 in human leukocyte antigen (HLA)-A*02:01-positive patients with HNSCC receiving 4 vaccinations of S-488210 at a dose of 1 mg each of the 3 peptides on a weekly basis
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Protection of trial subjects |
1st IDMC meeting:21 Oct 2013, Review of safety data for first 6 patients who received 4 weeks of treatment
2nd IDMC meeting: 25 Mar 2014: Review of safety data for first 6 patients and immune response data of those patients. No safety issues were noticed from both meetings.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
17 Jan 2013
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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 |
6 Months | ||
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 |
Belgium: 4
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Country: Number of subjects enrolled |
Germany: 3
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Worldwide total number of subjects |
7
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EEA total number of subjects |
7
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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) |
4
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From 65 to 84 years |
3
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85 years and over |
0
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Recruitment
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Recruitment details |
First site activated: 25 July 2012. Recruitment stopped 31 December 2013. Type of location was medical hospital. | ||||||||
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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 |
28 [1] | ||||||||
Number of subjects completed |
7 | ||||||||
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Pre-assignment subject non-completion reasons
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Reason: Number of subjects |
protocol exclusion criteria met: 21 | ||||||||
| Notes [1] - The number of subjects reported to have started the pre-assignment period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: Justification: The reported 24 patients were the number of patients planned per protocol. A total of 28 patients were enrolled, and of these patients at least 7 received 1 dose of the study drug. The error in the database occurs because Eudra pulled data from the initial Belgium CT application where the planned number of patients per protocol was filled in (24) and then it compared that number with the actual number of patients screened enrolled in phase 1 (28). |
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Period 1
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Period 1 title |
Step 1(Visit 1-4), Step 2(v5-withdrawal) (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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S-488210 | ||||||||
Arm description |
injection of S-488210 once a week over 4-week treatment period followed by extension period, and every 2 weeks after week 13 | ||||||||
Arm type |
Experimental | ||||||||
Investigational medicinal product name |
not available yet
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Investigational medicinal product code |
S-488210
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Other name |
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Pharmaceutical forms |
Powder for injection
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
3 mg per day
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Baseline characteristics reporting groups
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Reporting group title |
Step 1(Visit 1-4), Step 2(v5-withdrawal)
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Reporting group description |
Injection of S-488210 once a week over 4 weeks treatment period followed by extension period | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
safety analysis set
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Subject analysis set type |
Safety analysis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
All patients who received at least 1 dose of study drug
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Subject analysis set title |
full analysis set
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Subject analysis set type |
Full analysis | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
All patients who received at least 1 dose of study drug
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End points reporting groups
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Reporting group title |
S-488210
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Reporting group description |
injection of S-488210 once a week over 4-week treatment period followed by extension period, and every 2 weeks after week 13 | ||
Subject analysis set title |
safety analysis set
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
All patients who received at least 1 dose of study drug
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Subject analysis set title |
full analysis set
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
All patients who received at least 1 dose of study drug
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End point title |
The number and percentage of patients with at least 1 treatment-emergent AEs (TEAE) [1] | |||||||||
End point description |
Adverse events were assessed from the date the ICF was signed up to 30 days after the last dose of study drug. TEAE was defined as any event not present before exposure to study drug or any event already present that worsened in either intensity or frequency after exposure to study drug.
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End point type |
Primary
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End point timeframe |
Duration from the date the ICF was signed up to 30 days after the last dose of study drug
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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: Justification: Shionogi would not perform any statistical analysis as per protocol since Shionogi & Co, Ltd has decided to terminate phase 2 part because of changing the formula of the cancer peptide vaccine S-488210. |
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| Notes [2] - Patients experienced TEAEs [3] - Patients experienced TEAEs |
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| No statistical analyses for this end point | ||||||||||
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End point title |
Cytotoxic T Lymphocyte Induction Rate | |||||||||
End point description |
Cytotoxic T lymphocyte induction was defined as increased CTL activity compared with baseline
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End point type |
Secondary
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End point timeframe |
Every 4 week until 12 weeks
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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 |
Adverse events were assessed from the date the ICF was signed up to 30 days after the last dose of the study drug.
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Adverse event reporting additional description |
A treatment-emergent AE (TEAE) was defined as any event not present before exposure to study drug or any event already present that worsened in either intensity or frequency after exposure to study drug. Total No of TEAEs, No and % of patients with at least 1 TEAE were tabulated along with the No and % of patients by system/organ/class and pr term
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
17.0
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Reporting groups
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Reporting group title |
S-488210
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Reporting group description |
Injection of S-488210 once a week over 4 week treatment period followed by extension period | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 1% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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06 Feb 2013 |
Amendment 3, Protocol version 4.0
- Inclusion criterion 9 was updated to remove the upper age limit.
- Exclusion criterion 2 was updated to clarify that only patients with proof or suggestion of active infection will be excluded.
- Exclusion criterion 17 was updated to change the allowable time period for previous use of another investigational product from “within 60 days of enrollment” to “within 28 days of enrollment”. |
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21 Jun 2013 |
Amendment 4, Protocol version 5.0
• Exclusion criterion 3 was updated to clarify that the exclusion of patients with human papilloma virus-positive tumor applied to patients in the Phase 2 part of the study only. |
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16 Mar 2014 |
Amendment 5, Protocol version 6.0
• It was added that overall survival and progression-free survival will be assessed for the Phase 1 part 6 months after the last patient has completed Step 1 of the Phase 1 part. |
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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 | |||
