Clinical Trial Results:
An open label biomarker pilot study of the antitumoral acrivity of denosumab in the pre-operative setting of early breast cancer
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Summary
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EudraCT number |
2016-002678-11 |
Trial protocol |
ES |
Global end of trial date |
25 Jan 2022
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Results information
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Results version number |
v1(current) |
This version publication date |
06 Jul 2023
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First version publication date |
06 Jul 2023
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Other versions |
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Summary report(s) |
ICO_Final Report |
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 |
ICO-13-001
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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 |
Institut Catala d'Oncologia
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Sponsor organisation address |
Av. Gran Via 199-203, L'Hospitalet de Llobregat, Spain, 08908
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Public contact |
Gestora de proyectos, Institut Catala d'Oncologia, 34 932607139, cmoreno2@iconcologia.net
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Scientific contact |
Gestora de proyectos, Institut Catala d'Oncologia, 34 932607139, cmoreno2@iconcologia.net
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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 |
28 Feb 2023
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
25 Jan 2022
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Global end of trial reached? |
Yes
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Global end of trial date |
25 Jan 2022
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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 demonstrate the antiproliferative and/or pro-apoptotic activity of denosumab in early breast cancer.
If the Hypothesis of this study is proven right it will substantiate and provide rationale to the development of denosumab as an ant-cancer drug in breast cancer.
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Protection of trial subjects |
N/A
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
30 Apr 2018
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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 |
Spain: 58
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Worldwide total number of subjects |
58
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EEA total number of subjects |
58
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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) |
42
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From 65 to 84 years |
15
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85 years and over |
1
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Recruitment
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Recruitment details |
Subjects diagnosed with early, resectable, Her-2 negative breast cancer are candidates to this study. Once the informed consent form of this study is signed by the patients, a tumor biopsy and blood sample will be obtained (biopsy A). | ||||||||||||||||||
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Pre-assignment
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Screening details |
Subjects meeting the study eligibility criteria as assessed during the screening period should be randomized 2:1 into the two described cohorts within 7 days of planned initiation of study treatment. | ||||||||||||||||||
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Period 1
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Period 1 title |
Overall trial (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 |
Subject, Investigator | ||||||||||||||||||
Blinding implementation details |
This study will be a biomarker finding study. Laboratory investigators will be blinded to the randomization of the subject. The study team not involved in laboratory investigations will have access to the randomization of the subjects.
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Arms
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Are arms mutually exclusive |
No
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Arm title
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Arm A Denosumab | ||||||||||||||||||
Arm description |
Subjects are planned to be randomized into two cohorts (arm A and arm B) in a 2:1 fashion. Only those patients allocated to arm A will receive the study treatment with two doses of 120 mg sc of Deno-sumab on days 1 and 8, prior to surgery. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Denosumab
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection in vial
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Routes of administration |
Injection
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Dosage and administration details |
If the patients are considered eligible, after the screening period, two doses of subcutaneous Denosumab (120 mg) (d1, 8) will be administered.
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Arm title
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Arm B Observational | ||||||||||||||||||
Arm description |
- | ||||||||||||||||||
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 |
Overall trial
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Reporting group description |
- | |||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Arm A Denosumab
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Reporting group description |
Subjects are planned to be randomized into two cohorts (arm A and arm B) in a 2:1 fashion. Only those patients allocated to arm A will receive the study treatment with two doses of 120 mg sc of Deno-sumab on days 1 and 8, prior to surgery. | ||
Reporting group title |
Arm B Observational
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Reporting group description |
- | ||
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End point title |
Endpoints to evaluate the primary Objective | |||||||||
End point description |
Changes in the percentage of tumor cells expressing Ki67 and/or cleaved caspase 3 between Biopsy A (pre-treatment) and Biopsy B (post-treatment).
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End point type |
Primary
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End point timeframe |
Only subjects assigned to arm A will receive two doses of denosumab 120 mg sc, administered on days 1 and 8 stating 21 days (±7 days) prior to scheduled surgery.
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| Notes [1] - 60 patients were included as planned, however, only 58 patients were evaluable. |
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Statistical analysis title |
Ki67 | |||||||||
Comparison groups |
Arm A Denosumab v Arm B Observational
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Number of subjects included in analysis |
58
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Analysis specification |
Pre-specified
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Analysis type |
other [2] | |||||||||
P-value |
= 0.894 | |||||||||
Method |
t-test, 2-sided | |||||||||
Parameter type |
Mean difference (final values) | |||||||||
Confidence interval |
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| Notes [2] - Denosumab did not reduce tumor cell proliferation compared with control arm. Quantifications were performed blindly by two independent pathologists specialized in breast cancer. The percentage of tumor cells that express Ki67 increased in the experimental arm, but also in the control arm. |
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Statistical analysis title |
Cleaved_Caspase 3 | |||||||||
Comparison groups |
Arm A Denosumab v Arm B Observational
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Number of subjects included in analysis |
58
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Analysis specification |
Pre-specified
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Analysis type |
other [3] | |||||||||
P-value |
= 0.038 | |||||||||
Method |
t-test, 2-sided | |||||||||
Confidence interval |
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| Notes [3] - No increase in Cleaved-Caspase 3 were observed after denosumab. The findings are statistically significant, although marginally, and not clinically relevant. |
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Adverse events information
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Timeframe for reporting adverse events |
All Adverse events occurring out to 30 days following the completion of study treatment phase was reported. All “related” adverse events was reported within the period between 30 days after completion of study treatment.
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Assessment type |
Non-systematic | ||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
CTCAE | ||||||||||||||||||||
Dictionary version |
4.3
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Reporting groups
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Reporting group title |
Experimental
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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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15 Jun 2018 |
Change of an excipient (sorbitol) in the study drug formulation. |
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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 | |||
