Clinical Trial Results:
A Phase II Study of Palbociclib plus Fulvestrant versus Placebo plus Fulvestrant for pretreated patients with ER+/HER2- Metastatic Breast Cancer.
|
Summary
|
|
EudraCT number |
2014-005387-15 |
Trial protocol |
BE GB IT |
Global end of trial date |
22 Dec 2022
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
27 Mar 2024
|
First version publication date |
27 Mar 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 |
IBCSG 53-14
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
NCT02536742 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
Breast International Group: BIG_14-04, Pfizer Inc.: WI198393 | ||
|
Sponsors
|
|||
Sponsor organisation name |
ETOP IBCSG Partners Foundation
|
||
Sponsor organisation address |
Effingerstrasse 33, Bern, Switzerland, 3008
|
||
Public contact |
ETOP IBCSG Partners Regulatory Office, ETOP IBCSG Partners Foundation, +41 31 511 94 00, ibcsg-regulatory@etop.ibcsg.org
|
||
Scientific contact |
ETOP IBCSG Partners Regulatory Office, ETOP IBCSG Partners Foundation, +41 31 511 94 00, ibcsg-regulatory@etop.ibcsg.org
|
||
|
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 |
28 Aug 2020
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
28 Aug 2020
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
22 Dec 2022
|
||
Was the trial ended prematurely? |
No
|
||
|
General information about the trial
|
|||
Main objective of the trial |
This is a single-arm phase II trial for postmenopausal patients receiving fulvestrant and palbociclib for ER+ / HER2-negative metastatic or locally advanced breast cancer who have progressed under previous endocrine therapy. The primary objective is to interrogate in a prospective manner a series of potential biomarkers, which will be assessed for their association with progression-free survival (PFS).
|
||
Protection of trial subjects |
Participating institutions’ ethics committees or Institutional Review Boards approved the trial according to local laws and regulations. All patients gave written informed consent, and the trial was performed in compliance with the Helsinki Declaration. The Data Safety and Monitoring Board reviewed the data from this research throughout the study.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
04 Jan 2016
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
Yes
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
United Kingdom: 3
|
||
Country: Number of subjects enrolled |
Belgium: 75
|
||
Country: Number of subjects enrolled |
Italy: 46
|
||
Worldwide total number of subjects |
124
|
||
EEA total number of subjects |
121
|
||
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) |
79
|
||
From 65 to 84 years |
45
|
||
85 years and over |
0
|
||
|
|||||||||||||
|
Recruitment
|
|||||||||||||
Recruitment details |
The first patient was registered on 29 August 2016 (randomized on 30 August 2016). The last patient was registered on 14 June 2019. The final accrual was 124 patients. | ||||||||||||
|
Pre-assignment
|
|||||||||||||
Screening details |
1 patient was registered but not enrolled under the original protocol and is not included. | ||||||||||||
|
Period 1
|
|||||||||||||
Period 1 title |
Overall Study (overall period)
|
||||||||||||
Is this the baseline period? |
Yes | ||||||||||||
Allocation method |
Not applicable
|
||||||||||||
Blinding used |
Not blinded | ||||||||||||
Blinding implementation details |
no blinding
|
||||||||||||
|
Arms
|
|||||||||||||
|
Arm title
|
Fulvestrant + palbociclib | ||||||||||||
Arm description |
Patients are treated with fulvestrant (500mg im administered on days 1 and 15 of cycle 1, then on day 1 of every 28 days cycle) plus palbociclib (125mg po per day, continuously for 3 weeks followed by 1 week off; repeated at each subsequent cycle of 28 days). Patients will receive the treatment until progression, lack of tolerability, or patient declines further protocol treatment. Fulvestrant is used in accordance with the currently approved SPC and regarded as non-investigational medicinal product (NIMPs), in accordance with the applicable EU legislation. | ||||||||||||
Arm type |
Experimental | ||||||||||||
Investigational medicinal product name |
Palbociclib
|
||||||||||||
Investigational medicinal product code |
|||||||||||||
Other name |
|||||||||||||
Pharmaceutical forms |
Capsule
|
||||||||||||
Routes of administration |
Oral use
|
||||||||||||
Dosage and administration details |
Palbociclib was administered orally at a dose of 125 mg per day continuously for 3 weeks followed by 1 week off; repeated at each subsequent cycle of 28 days.
|
||||||||||||
|
|||||||||||||
|
||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
||||||||||||||||||||||||||||||||||
Reporting group title |
Overall Study
|
|||||||||||||||||||||||||||||||||
Reporting group description |
- | |||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||
|
Subject analysis sets
|
||||||||||||||||||||||||||||||||||
Subject analysis set title |
Analysis Population
|
|||||||||||||||||||||||||||||||||
Subject analysis set type |
Per protocol | |||||||||||||||||||||||||||||||||
Subject analysis set description |
There were 2 patients excluded who did not start protocol therapy or did not have the target disease, thus 122 patients in the clinical population.
|
|||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
Fulvestrant + palbociclib
|
||
Reporting group description |
Patients are treated with fulvestrant (500mg im administered on days 1 and 15 of cycle 1, then on day 1 of every 28 days cycle) plus palbociclib (125mg po per day, continuously for 3 weeks followed by 1 week off; repeated at each subsequent cycle of 28 days). Patients will receive the treatment until progression, lack of tolerability, or patient declines further protocol treatment. Fulvestrant is used in accordance with the currently approved SPC and regarded as non-investigational medicinal product (NIMPs), in accordance with the applicable EU legislation. | ||
Subject analysis set title |
Analysis Population
|
||
Subject analysis set type |
Per protocol | ||
Subject analysis set description |
There were 2 patients excluded who did not start protocol therapy or did not have the target disease, thus 122 patients in the clinical population.
|
||
|
|||||||||||
End point title |
Number of Participants With and Without Progression Free Survival (PFS) Events [1] | ||||||||||
End point description |
Time from treatment initiation until documented disease progression according to RECIST 1.1 or death, whichever occurs first
|
||||||||||
End point type |
Primary
|
||||||||||
End point timeframe |
Maximum 36 months
|
||||||||||
| 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: No statistical analysis done |
|||||||||||
|
|||||||||||
| No statistical analyses for this end point | |||||||||||
|
|||||||||||||||
End point title |
Best Overall Response | ||||||||||||||
End point description |
Best overall response is based on RECIST (Response evaluation criteria in solid tumors) 1.1 criteria and is defined as best response recorded from enrollment across all time points until disease progression. Confirmation of partial response (PR) or complete response (CR) by an additional scan was not requested in this trial (rationale: initially because of randomized placebo-controlled design; subsequently because no hypothesis testing of progression-free survival, PFS, distribution relative to an historical control).
|
||||||||||||||
End point type |
Secondary
|
||||||||||||||
End point timeframe |
From date of enrolment until patient's end of treatment visit (or a maximum of 12 months after EoT in the absence of tumor progression), assessed up to 48 months.
|
||||||||||||||
|
|||||||||||||||
| No statistical analyses for this end point | |||||||||||||||
|
|||||||||||
End point title |
Best Overall Response of Complete Response (CR) or Partial Response (PR) or Stable Disease (SD) | ||||||||||
End point description |
Disease control is defined as best overall response of complete response (CR) or partial response (PR), or stable disease (SD) (or non-CR/non-PD, progressive disease, in the case of non-measurable disease only) lasting for at least 24 weeks, measured from enrollment until first documentation of progressive disease
|
||||||||||
End point type |
Secondary
|
||||||||||
End point timeframe |
From date of enrolment until patient's end of treatment visit (or a maximum of 12 months after EoT in the absence of tumor progression), assessed up to 48 months.
|
||||||||||
|
|||||||||||
| No statistical analyses for this end point | |||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Maximum 36 months
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse event reporting additional description |
AEs were collected using Common Terminology Criteria for Adverse Events (CTCAE) v4.0. AEs were collected at the end of each cycle, from first dose of trial treatment until 28 days after all treatment discontinuation.
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
NCI CTCAE | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
4.0
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Analysis Population
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
Palbociclib plus Fulvestrant Palbociclib: 125 mg, orally, daily for 3 weeks followed by 1 week off; repeated at every 28 days cycle until progression, lack of tolerability, or patient declines further protocol treatment. Fulvestrant: 500mg, intramuscularly on days 1 and 15 of cycle 1, then on day 1 (+/- 3 days) of every 28 days cycle until progression, lack of tolerability, or patient declines further protocol treatment. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 |
||
26 Jan 2017 |
Based on recommendations from the IBCSG DSMC, IBCSG decided to close the placebo arm of the PYTHIA study on 23 November 2016. The decision was taken after reviewing the current accrual (1 patient randomized since activation of the first center on 04 May 2016) and following the recent announcement by Pfizer that palbociclib received approval in the EU for the treatment of women with HR+/HER2- locally advanced or metastatic breast cancer. The approval also covers the use of palbociclib in combination with fulvestrant in women who have received prior endocrine therapy. The DSMC recommended to unblind the treatment of the one patient randomized, to inform the patient about her treatment assignment, and to offer her palbociclib if she has been randomized to placebo (n.b., per the code break form in the database, she had been assigned to palbociclib). Patients already consented and all future patients were to be informed of the closing of the placebo arm and that they would receive palbociclib and fulvestrant. The PYTHIA trial remained open for patient enrollment in Belgium but not in Italy.
Amendment 1, which was distributed on 20 February 2017, implemented the design change to single-arm trial of 120 patients, with revised primary objective.
|
||
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. | |||
| None reported | |||
