Trial Review

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02019277




Registration number
NCT02019277
Ethics application status
Date submitted
18/12/2013
Date registered
24/12/2013
Date last updated
13/09/2018

Titles & IDs
Public title
A Study of Pertuzumab and Trastuzumab Subcutaneous (SC) Treatment in Combination With a Taxane in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Metastatic Breast Cancer
Scientific title
An Open-label, Multicentre, Phase IIIb Study With Intravenous Administration of Pertuzumab, Subcutaneous Trastuzumab, and a Taxane in Patients With HER2-positive Metastatic Breast Cancer
Secondary ID [1] 0 0
ML28784
Universal Trial Number (UTN)
Trial acronym
SAPPHIRE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Breast

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Docetaxel
Treatment: Drugs - Nab-paclitaxel
Treatment: Drugs - Paclitaxel
Treatment: Drugs - Pertuzumab
Treatment: Drugs - Trastuzumab

Experimental: Trastuzumab SC, Pertuzumab, and Taxane - Participants will receive pertuzumab, trastuzumab and a taxane (docetaxel, paclitaxel or nab-paclitaxel) once every 3 weeks (21-day cycles). Choice of taxane will be at the discretion of the investigator and administered per routine clinical practices and local prescribing instructions.


Treatment: Drugs: Docetaxel
Dosing regimen to be determined by the investigator, routine clinical practices.

Treatment: Drugs: Nab-paclitaxel
Dosing regimen to be determined by the investigator, routine clinical practices.

Treatment: Drugs: Paclitaxel
Dosing regimen to be determined by the investigator, routine clinical practices.

Treatment: Drugs: Pertuzumab
Pertuzumab will be administered on Day 1 of the first treatment cycle as a loading dose of 840 mg, followed by 420 mg as an IV infusion every 3 weeks.

Treatment: Drugs: Trastuzumab
Trastuzumab will be administered at a fixed dose of 600 mg SC every 3 weeks.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With Adverse Events (AEs) and Serious AEs
Timepoint [1] 0 0
Baseline up to 28 days after last study drug administration (up to 36 months)
Primary outcome [2] 0 0
Percentage of Participants With AEs by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0 Intensity Grades
Timepoint [2] 0 0
Baseline up to 28 days after last study drug administration (up to 36 months)
Primary outcome [3] 0 0
Percentage of Participants With AEs Leading to Premature Discontinuation of Investigational Medicinal Products (IMPs)
Timepoint [3] 0 0
Baseline up to 28 days after last study drug administration (up to 36 months)
Primary outcome [4] 0 0
Percentage of Participants With AEs of Suspected Cardiac Origin, by New York Heart Association Classification (NYHA)
Timepoint [4] 0 0
Baseline up to 28 days after last study drug administration (up to 36 months)
Primary outcome [5] 0 0
Percentage of Participants With Left Ventricular Ejection Fraction (LVEF) Below 50%
Timepoint [5] 0 0
Baseline up to 28 days after last study drug administration (up to 36 months)
Secondary outcome [1] 0 0
Percentage of Participants With Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Timepoint [1] 0 0
Baseline up to withdrawal of consent, loss to follow-up, disease progression, death, or study end (up to approximately 36 months)
Secondary outcome [2] 0 0
Percentage of Participants With PD (Assessed According to RECIST Version 1.1) or Death Due to Any Cause
Timepoint [2] 0 0
Baseline up to withdrawal of consent, loss to follow-up, disease progression, death, or study end (up to approximately 36 months)
Secondary outcome [3] 0 0
Progression-free Survival (PFS) Assessed According to RECIST Version 1.1
Timepoint [3] 0 0
Baseline up to withdrawal of consent, loss to follow-up, disease progression, death, or study end (up to approximately 36 months)
Secondary outcome [4] 0 0
Percentage of Participants Who Died Due to Any Cause
Timepoint [4] 0 0
Baseline up to withdrawal of consent, loss to follow-up, disease progression, death, or study end (up to approximately 36 months)
Secondary outcome [5] 0 0
Overall Survival (OS)
Timepoint [5] 0 0
Baseline up to withdrawal of consent, loss to follow-up, disease progression, death, or study end (up to approximately 36 months)
Secondary outcome [6] 0 0
Event-free Survival (EFS) Assessed According to RECIST Version 1.1
Timepoint [6] 0 0
Baseline up to withdrawal of consent, loss to follow-up, disease progression, death, or study end (up to approximately 36 months)
Secondary outcome [7] 0 0
Percentage of Participants Who Died During Receiving Second-Line of Treatment
Timepoint [7] 0 0
From start of second-line of treatment (any time from baseline up to 35 months) up to death due to any cause or study end (up to approximately 36 months)
Secondary outcome [8] 0 0
OS During Second-Line of Treatment
Timepoint [8] 0 0
From start of second-line of treatment (any time from baseline up to 35 months) up to death due to any cause or study end (up to approximately 36 months)
Secondary outcome [9] 0 0
Number of Participants Receiving Second-Line Treatment by Treatment Type
Timepoint [9] 0 0
Baseline up to approximately 35 months

Eligibility
Key inclusion criteria
* HER2-positive disease, with an immunohistochemistry score of 3+ or in situ hybridization (ISH)-positive on primary tumor or metastatic site
* Histologically or cytologically confirmed adenocarcinoma of the breast with metastatic disease with at least one measurable lesion and/or non-measurable disease according to RECIST Version 1.1
* Eastern Cooperative Oncology Group (ECOG) performance status 0-2 for participants who will receive paclitaxel or nab-paclitaxel chemotherapy and ECOG 0-1 for participants who will receive docetaxel chemotherapy
* LVEF of greater than or equal to (>=) 50 percent (%) measured by ECHO or MUGA scan before the first doses of pertuzumab and trastuzumab
* Previous use of either adjuvant or neoadjuvant anti-HER2 therapy is allowed
* Hormonal therapy will be allowed as per institutional guidelines. Hormonal therapy cannot be administered in combination with taxane therapy
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Previous systemic non-hormonal anticancer therapy for treatment of mBC
* History of other cancers. Participants with curatively treated carcinoma in situ of the cervix or basal cell carcinoma and participants with other curatively-treated cancers who have been disease-free for at least 5 years are eligible. Participants with previous ductal carcinoma in situ (DCIS) of the breast are also eligible for the study
* Pregnant or breastfeeding women. Positive serum pregnancy test in women of childbearing potential, premenopausal or less than 12 months of amenorrhea post-menopause, within 7 days before the first dose of pertuzumab and trastuzumab
* Current peripheral neuropathy of Grade 3 or greater (National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] Version 4.0)
* Radiographic evidence of central nervous system (CNS) metastases as assessed by computed tomography (CT) or magnetic resonance imaging (MRI), unless they have been treated and have been stable for at least 3 months and do not require ongoing corticosteroid treatment
* Participants with other concurrent serious diseases that may interfere with planned treatment, including severe pulmonary conditions/illness
* Inadequate organ function
* Serious cardiac illness or medical conditions that would preclude the use of trastuzumab
* Participants with severe dyspnea at rest or requiring supplementary oxygen therapy
* Concurrent enrollment in another clinical study using an investigational anti-cancer treatment, within 28 days before the first doses of trastuzumab and pertuzumab

Study design
Purpose of the study
Treatment
Allocation to intervention
NA
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
5/12/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
4/11/2016
Sample size
Target
Accrual to date
Final
50
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,TAS,VIC,WA
Recruitment hospital [1] 0 0
St George Hospital; Cancer Care Centre - Kogarah
Recruitment hospital [2] 0 0
Port Macquarie Base Hospital - Port Macquarie
Recruitment hospital [3] 0 0
Newcastle Mater Misericordiae Hospital; Oncology - Waratah
Recruitment hospital [4] 0 0
Mater Hospital; Cancer Services - South Brisbane
Recruitment hospital [5] 0 0
Princess Alexandra Hospital Woolloongabba; Clinical Hematology and Medical Oncology - Woolloongabba
Recruitment hospital [6] 0 0
Lyell McEwin Hospital - Adelaide
Recruitment hospital [7] 0 0
Launceston General Hospital - Launceston
Recruitment hospital [8] 0 0
Bendigo Hospital; Oncology - Bendigo
Recruitment hospital [9] 0 0
Monash Medical Centre; Oncology - Clayton
Recruitment hospital [10] 0 0
Geelong Hospital; Andrew Love Cancer Centre - Geelong
Recruitment hospital [11] 0 0
Royal Melbourne Hospital; Hematology and Medical Oncology - Parkville
Recruitment hospital [12] 0 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [13] 0 0
St John of God Murdoch Hospital; Oncology West - Murdoch
Recruitment postcode(s) [1] 0 0
2217 - Kogarah
Recruitment postcode(s) [2] 0 0
2444 - Port Macquarie
Recruitment postcode(s) [3] 0 0
2298 - Waratah
Recruitment postcode(s) [4] 0 0
4101 - South Brisbane
Recruitment postcode(s) [5] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [6] 0 0
5112 - Adelaide
Recruitment postcode(s) [7] 0 0
7250 - Launceston
Recruitment postcode(s) [8] 0 0
3550 - Bendigo
Recruitment postcode(s) [9] 0 0
3168 - Clayton
Recruitment postcode(s) [10] 0 0
3220 - Geelong
Recruitment postcode(s) [11] 0 0
3052 - Parkville
Recruitment postcode(s) [12] 0 0
6150 - Murdoch

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT02019277