Clinical Trial Results:
A prospective, multicenter, single-arm, phase II study to evaluate the safety of neoadjuvant liposomal doxorubicin (Myocet®) plus paclitaxel, trastuzumab, and pertuzumab in patients with operable HER2-positive breast cancer
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Summary
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EudraCT number |
2012-001201-24 |
Trial protocol |
ES |
Global end of trial date |
18 Jan 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
27 Apr 2022
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First version publication date |
27 Apr 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 |
SOLTI-1002
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01669239 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
SOLTI
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Sponsor organisation address |
C/ Balmes 89 3-7, Barcelona, Spain, 08008
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Public contact |
Investigación Clinica, SOLTI, +34 933436302, regsolti@gruposolti.org
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Scientific contact |
Investigación Clinica, SOLTI, +34 933436302, regsolti@gruposolti.org
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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 |
05 Apr 2017
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
18 Jan 2016
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Global end of trial reached? |
Yes
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Global end of trial date |
18 Jan 2016
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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 assess cardiac safety, measured by the incidence of type A (symptomatic cardiac failure) and type B (asymptomatic left ventricular ejection fraction [LVEF] decline) cardiac events, of the combination regimen of liposomal doxorubicin, paclitaxel, trastuzumab, and pertuzumab when given as neoadjuvant therapy for patients with operable HER2-positive BC
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Protection of trial subjects |
The screening period included the 28 days prior to the start of the treatment under study to perform the scheduled procedures.
During neoadjuvant treatment also assessment procedures were carried out during Visits 2 to 7
A preoperative visit was scheduled within 7 days prior to surgery.
Peri-Surgery Visit: Surgery was planned for patients whose tumor was considered operable based on standard local practice within 4 to 6 weeks after completion of treatment or discontinuation of neoadjuvant treatment due to unacceptable toxicity or unacceptable or withdrawal of consent. Tumor tissue was collected from the surgical specimen for pathologic response analysis and the type of breast surgery was recorded.
The operated patients returned to the clinic two weeks (± 7 days) after the surgery.
Thereafter, patients were followed every 3 months until completing 12 months from the start of neoadjuvant treatment.
Approximately 28 days after the last study visit, a final safety assessment was performed. Patients were followed up every 3 months until 1 year after initiation of study treatment to collect cardiac safety data (follow-up period).
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
10 Sep 2012
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Long term follow-up planned |
No
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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 |
Spain: 83
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Worldwide total number of subjects |
83
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EEA total number of subjects |
83
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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) |
75
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From 65 to 84 years |
8
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85 years and over |
0
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Recruitment
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Recruitment details |
Between June 2013 and January 2015, 93 patients were proposed for study, of which 10 were screening failures, so 83 patients were finally assigned to treatment. A total of 20 spanish hospitals participated. | ||||||||||||||||||
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Pre-assignment
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Screening details |
Female patients (18 and 74 years old) with untreated HER2 positive histologically confirmed invasive breast carcinoma (stages II to IIIB) and ECOG 0-1 and with no clinical or radiological evidence of metastasis (stage IV), no previous chemotherapy, RT or CM surgery (except tumor excision on the contralateral breast) or concurrent secondary cancer. | ||||||||||||||||||
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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 |
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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Assigned to study treatment | ||||||||||||||||||
Arm description |
- | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Myocet®
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Investigational medicinal product code |
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Other name |
Doxorubicin HCL Liposome
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Pharmaceutical forms |
Powder, dispersion and solvent for concentrate for dispersion for infusion
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Routes of administration |
Injection , Infusion , Intravenous use
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Dosage and administration details |
Myocet® was administered at a dose of 50 mg/m2 as a 1-hour intravenous infusion on Day 1 of each 3-week cycle. Treatment with Myocet® was administered every 3 weeks for 6 cycles.
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Investigational medicinal product name |
Herceptin®
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Investigational medicinal product code |
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Other name |
Trastuzumab
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Pharmaceutical forms |
Powder for concentrate for solution for infusion
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Routes of administration |
Infusion
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Dosage and administration details |
One vial contains 150 mg of trastuzumab. Trastuzumab reconstituted solution contains 21 mg/mL of trastuzumab. Trastuzumab was administered weekly, with a loading dose of 4 mg/kg in the first infusion and 2 mg/kg in subsequent infusions.
During neoadjuvant treatment, trastuzumab was administered weekly for 6 cycles (18 weeks). The administration of adjuvant trastuzumab was recommended for at least 12 months from the first administration, based on currently acceptable practice.
Trastuzumab administrations during the adjuvant period should be given at one-week intervals or
or 3-week intervals. However, adjuvant treatment with trastuzumab was outside the scope of this protocol.
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Investigational medicinal product name |
Perjeta®
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Investigational medicinal product code |
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Other name |
Pertuzumab
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Pharmaceutical forms |
Concentrate for solution for infusion
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Routes of administration |
Infusion , Intravenous use
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Dosage and administration details |
Pertuzumab is supplied as a single-use formulation containing 30 mg/mL of pertuzumab in 20 mM L-histidine-acetate (pH 6.0), 120 mM sucrose and 0.02% polysorbate 20 at 0.02%. Each 20 cc vial (14.0 mL of solution per vial) contains approximately 420 mg of pertuzumab. The entire volume of the bag should be administered as a continuous IV infusion. During neoadjuvant treatment, pertuzumab was administered every 3 weeks for 6 cycles. Pertuzumab was administered on Day 1 of Cycle 1 at the required loading dose of 840 mg as an IV infusion. Three weeks (21 days) after the first dose of pertuzumab, and then every 3 weeks thereafter, pertuzumab was administered at a dose of 420 mg as an IV infusion.
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Investigational medicinal product name |
Taxol®
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Investigational medicinal product code |
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Other name |
Paclitaxel
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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 |
The ingredients per milliliter are: l6 mg paclitaxel, 527 mg polyoxyethylated castor oil and 49.7% dehydrated alcohol. Paclitaxel should be diluted before infusion with sodium chloride 0.9% for injection, USP; 5% dextrose for injection, USP; dextrose 5% and sodium chloride 0.9% for Ringer's injection to a final concentration of 0.3 to 1.2 mg/mL.
Paclitaxel treatment was administered weekly for 6 cycles (18 weeks). Paclitaxel was administered at a dose of 80 mg/m2 intravenously for 1 hour every week.
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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 |
Assigned to study treatment
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Reporting group description |
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Subject analysis set title |
intent–to-treat population
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
All recruited patients were included in the intention-to-treat population.
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Subject analysis set title |
Per Protocol (PP) population
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Per-protocol analysis population: Patients were included in the per-protocol analysis population if they met ALL of the following criteria:
- Have received ≥ 3 cycles of the study medication (in neoadjuvant format) and
- Had not received any other antineoplastic treatment (drugs not included in the study or radiotherapy) and
- Have undergone surgery.
This analysis was only performed if this population differed from the IDT ≥ 10%.
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Subject analysis set title |
Safety population
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
The safety population includes patients who have received at least one dose of the study treatmentand have completed the safety assessment at the time of enrollment.
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End point title |
Cardiac adverse events [1] | ||||||||||
End point description |
The main objective of the study is to evaluate cardiac safety, as measured by the incidence of type A (symptomatic heart failure) and type B (asymptomatic reduction in left ventricular ejection fraction [LVEF]), of the combination regimen of liposomal doxorubicin, paclitaxel, trastuzumab and pertuzumab neoadjuvant therapy in patients with non-metastatic HER2-positive CM.
The safety population includes patients who have received at least one dose of the study treatment and have completed the safety assessment at the time of inclusion.
With 83 patients enrolled, no episode of symptomatic heart failure was observed and only 3 patients had a type B cardiac event.
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End point type |
Primary
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End point timeframe |
Overall study
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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: This non-inferiority study was designed to have 80% statistical power in testing the null hypothesis that the combination would result in a higher rate of cardiac events than the historical value (18%) vs. a non-inferior rate of cardiac events, with a one-sided significance level of 5%. All safety parameters will be summarized and presented in tables based on the safety population. population. |
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| No statistical analyses for this end point | |||||||||||
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End point title |
Complete Pathological Response | ||||||||
End point description |
The pathologic complete response rate determined the primary efficacy endpoint of the study and was assessed at the local level after surgery.
Complete Pathologic Breast Response (CPBR) was defined as the complete absence of invasive breast cancer according to the NSABP algorithm, regardless of axillary status and the presence of carcinoma in situ, assessed after the 6 cycles of treatment and surgery, or after withdrawal from the study, whichever comes first.
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End point type |
Secondary
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End point timeframe |
After surgery
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| No statistical analyses for this end point | |||||||||
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End point title |
Complete Pathologic Response in Breast and Axilla (PCRMA) | ||||||||
End point description |
Complete Pathologic Response in Breast and Axilla (PCRMA) was defined as the absence of invasive tumor cells in the breast and in all axillary lymph nodes removed, assessed after 6 cycles of treatment and surgery, or after withdrawal from the study, whichever comes first.
Nodal stages pN0(i-), pN0(i+), pN0(mol-) and pN0(mol+) were considered pN0.
The rate of RPCMA is summarized as the percentage (%) of patients meeting the criterion, with the exact 95% confidence interval.
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End point type |
Secondary
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End point timeframe |
After surgery
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| No statistical analyses for this end point | |||||||||
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End point title |
Overall response rate (ORR) | ||||||||||||||
End point description |
The clinical tumor response evaluates efficacy before surgery (pre-surgery), and is classified according to the RECIST 1.1 criteria.
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End point type |
Secondary
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End point timeframe |
Before surgery
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Objective Clinical Response Rate | ||||||||
End point description |
The Objective Clinical Response Rate (ORR) was defined as the overall response before surgery equal to complete response (CR) or partial response (PR).
The ORR is summarized as the percentage (%) of patients meeting the definition, with the confidence interval (%) of patients meeting the definition, with the exact 95% confidence interval.
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End point type |
Secondary
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End point timeframe |
Before surgery
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| No statistical analyses for this end point | |||||||||
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End point title |
Clinical Benefit | ||||||||
End point description |
Clinical Benefit (CB) was defined as the overall response before surgery equal to complete response (CR) or partial response (PR) or stable disease (SD).
The CB is summarized with the percentage (%) of patients meeting the definition, with the exact confidence interval of 95%
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End point type |
Secondary
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End point timeframe |
Before surgery
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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 |
Overall study
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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 |
18.0
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Reporting groups
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Reporting group title |
Safety Population
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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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05 Dec 2012 |
Protocol v.2.0_19-Jul-2012 |
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18 Dec 2013 |
Protocol v.3.0_17-oct-2013 |
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22 Jul 2015 |
Protocol v.4.0_20-may-2015 |
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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 | |||
