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Breast CancerPhase 3SAPPHIRENCT02019277

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

A Phase 3 study testing Docetaxel, Nab-paclitaxel and Paclitaxel in people with Breast Cancer, run by Hoffmann-La Roche at 13 sites in Australia.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This open-label, multicenter, Phase IIIb study will assess the safety, tolerability and efficacy of a combination therapy of intravenous (IV) pertuzumab (Perjeta), trastuzumab (Herceptin) SC, and taxane chemotherapy (docetaxel, paclitaxel or nab-paclitaxel) as first-line therapy in participants with HER2-positive… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Breast Cancer
What is being tested?
Docetaxel, Nab-paclitaxel and Paclitaxel
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
13 sitesAustralia
Study dates
5 Dec 2013to 4 Nov 2016
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

13 sites in 1 country.

13 sites in 1 country

Australia13 sites

  • Lyell McEwin Hospital

    Adelaide, South Australia, 5112

  • Bendigo Hospital; Oncology

    Bendigo, Victoria, 3550

  • Monash Medical Centre; Oncology

    Clayton, Victoria, 3168

  • Geelong Hospital; Andrew Love Cancer Centre

    Geelong, Victoria, 3220

  • St George Hospital; Cancer Care Centre

    Kogarah, New South Wales, 2217

  • Launceston General Hospital

    Launceston, Tasmania, 7250

  • Fiona Stanley Hospital

    Murdoch, Western Australia, 6150

  • St John of God Murdoch Hospital; Oncology West

    Murdoch, Western Australia, 6150

  • Royal Melbourne Hospital; Hematology and Medical Oncology

    Parkville, Victoria, 3052

  • Port Macquarie Base Hospital

    Port Macquarie, New South Wales, 2444

  • Mater Hospital; Cancer Services

    South Brisbane, Queensland, 4101

  • Newcastle Mater Misericordiae Hospital; Oncology

    Waratah, New South Wales, 2298

  • Princess Alexandra Hospital Woolloongabba; Clinical Hematology and Medical Oncology

    Woolloongabba, Queensland, 4102

Other trials in Australia

About this study

Official 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

This open-label, multicenter, Phase IIIb study will assess the safety, tolerability and efficacy of a combination therapy of intravenous (IV) pertuzumab (Perjeta), trastuzumab (Herceptin) SC, and taxane chemotherapy (docetaxel, paclitaxel or nab-paclitaxel) as first-line therapy in participants with HER2-positive metastatic breast cancer (mBC). All participants will be treated with 3-week cycles of pertuzumab IV (840 milligrams [mg] first dose; subsequent doses of 420 mg) and trastuzumab SC (600 milligrams [mg]). The taxane treatment regimen will be determined by the investigator. Participants will continue therapy until disease progression, unacceptable toxicity, or the participant withdraws consent, whichever occurs first.

Conditions
Breast Cancer
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DocetaxelDrug

    Dosing regimen to be determined by the investigator, routine clinical practices.

  • Nab-paclitaxelDrug

    Dosing regimen to be determined by the investigator, routine clinical practices.

  • PaclitaxelDrug

    Dosing regimen to be determined by the investigator, routine clinical practices.

  • PertuzumabDrug

    Also called Perjeta

    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.

  • TrastuzumabDrug

    Also called Herceptin

    Trastuzumab will be administered at a fixed dose of 600 mg SC every 3 weeks.

Study groups in NCT02019277
Study groupRoleWhat they receive
Trastuzumab SC, Pertuzumab, and TaxaneExperimentalParticipants 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.
Receives: Drug: Docetaxel; Drug: Nab-paclitaxel; Drug: Paclitaxel; Drug: Pertuzumab; Drug: Trastuzumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants With Adverse Events (AEs) and Serious AEs

    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Percentage of participants with AEs and SAEs was reported. AEs included both SAEs and non-SAEs. The 95% confidence interval (CI) was computed using Clopper-Pearson method.

    Measured: Baseline up to 28 days after last study drug administration (up to 36 months)

  2. Percentage of Participants With AEs by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0 Intensity Grades

    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Intensity of AEs were graded according to NCI CTCAE version 4.0 on a 5-point scale: Grade 1=Mild, intervention not indicated; Grade 2=Moderate, local or noninvasive intervention indicated; Grade 3=Severe or medically significant but not immediately life-threatening; Grade 4= Life-threatening consequences, urgent intervention indicated; and Grade 5=Death related to AE. Percentage of participants with AEs by maximum severity grades was reported.

    Measured: Baseline up to 28 days after last study drug administration (up to 36 months)

  3. Percentage of Participants With AEs Leading to Premature Discontinuation of Investigational Medicinal Products (IMPs)

    An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Percentage of participants with AEs leading to premature discontinuation of IMPs (pertuzumab and trastuzumab) was reported. AEs included both SAEs and non-SAEs. The 95% CI was computed using Clopper-Pearson method.

    Measured: Baseline up to 28 days after last study drug administration (up to 36 months)

  4. Percentage of Participants With AEs of Suspected Cardiac Origin, by New York Heart Association Classification (NYHA)

    NYHA functional classification includes: Class I (no limitation in physical activity; ordinary physical activity does not cause fatigue, breathlessness or palpitation), Class II (slight limitation of physical activity; ordinary physical activity results in fatigue, palpitation, breathlessness or angina pectoris), Class III (marked limitation of physical activity; less than ordinary activity will lead to symptomatically 'moderate' heart failure) and Class IV (inability to carry out any physical activity without discomfort; symptoms of congestive cardiac failure are present even at rest). Percentage of participants with AEs suspected to be of cardiac origin by maximum NYHA classification was reported.

    Measured: Baseline up to 28 days after last study drug administration (up to 36 months)

  5. Percentage of Participants With Left Ventricular Ejection Fraction (LVEF) Below 50%

    LVEF was assessed using echocardiography (ECHO) or multiple-gated acquisition (MUGA) scans. Percentage of participants with LVEF below 50% at any time during the study was reported.

    Measured: Baseline up to 28 days after last study drug administration (up to 36 months)

Secondary outcomes (9)

  1. 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

    BOR was defined as a confirmed CR or PR. All measurable lesions up to a maximum of 2 lesions per organ and 5 in total were identified as target lesions (TLs) and recorded at baseline. A sum of the diameters (longest for non-nodal lesions, short axis [SA] for nodal lesions) for all TLs was calculated as baseline sum of diameters (SD). All other lesions (or sites of disease) were identified as non-TLs and were recorded at baseline. CR was defined as the disappearance of all TLs and SA reduction to less than (<) 10 millimeter (mm) for nodal TLs/ non-TLs. PR was defined as greater than or equal to (>/=) 30% decrease in SD of TLs, taking as reference the baseline SD. Confirmation of response at a consecutive tumor assessment at least 4 weeks apart was required. The 95% CI was computed using Clopper-Pearson method.

    Measured: Baseline up to withdrawal of consent, loss to follow-up, disease progression, death, or study end (up to approximately 36 months)

  2. Percentage of Participants With PD (Assessed According to RECIST Version 1.1) or Death Due to Any Cause

    For TLs, PD was defined as >/=20% relative increase and >/=5 mm of absolute increase in the SD, taking as reference the smallest SD recorded since treatment started or the appearance of 1 or more new lesions. For non-TLs, PD was defined as appearance of 1 or more new lesions and/or unequivocal progression of existing non-TLs.

    Measured: Baseline up to withdrawal of consent, loss to follow-up, disease progression, death, or study end (up to approximately 36 months)

  3. Progression-free Survival (PFS) Assessed According to RECIST Version 1.1

    PFS was defined as the time from start of treatment until first documented PD or death from any cause, whichever occurred first. Participants without PD, death, or who were lost to follow-up at the time of analysis were censored at the date of the last tumor assessment when non-progression was documented or at the last date of follow-up, whichever was last. Participants without tumor assessment data after the baseline were censored at baseline unless death occurred before first scheduled tumor assessment. PD was defined as >/=20% relative increase and >/=5 mm of absolute increase in the SD of TLs, taking as reference the smallest SD recorded since treatment started, and/or unequivocal progression of existing non-TLs, or appearance of 1 or more new lesions. Median PFS was estimated using Kaplan-Meier method. The 95% CI was computed using Brookmeyer and Crowley method.

    Measured: Baseline up to withdrawal of consent, loss to follow-up, disease progression, death, or study end (up to approximately 36 months)

  4. Percentage of Participants Who Died Due to Any Cause

    Percentage of participants who died due to any cause during the study was reported.

    Measured: Baseline up to withdrawal of consent, loss to follow-up, disease progression, death, or study end (up to approximately 36 months)

  5. Overall Survival (OS)

    The OS was defined as the time from the start of treatment until death from any cause. Participants alive at the time of analysis and participants who were lost to follow-up were censored at their last clinical assessment date. Median OS was estimated using Kaplan-Meier method. The 95% CI was computed using Brookmeyer and Crowley method.

    Measured: Baseline up to withdrawal of consent, loss to follow-up, disease progression, death, or study end (up to approximately 36 months)

  6. Event-free Survival (EFS) Assessed According to RECIST Version 1.1

    EFS was defined as the time from the start of treatment until the first documented initiation of non-protocol-specified treatment for metastatic breast cancer, PD, or death from any cause, whichever occurred first. Participants without treatment change, PD, death, or who were lost to follow-up at the time of analysis were censored at the date of the last tumor assessment when non-progression was documented or at the last date of follow-up, whichever was last. Participants without tumor assessment after baseline were censored at baseline unless death occurred before first scheduled tumor assessment. PD was defined as >/=20% relative increase and >/=5 mm of absolute increase in the SD of TLs, taking as reference the smallest SD recorded since treatment started, and/or unequivocal progression of existing non-TLs, or appearance of 1 or more new lesions. Median EFS was estimated using Kaplan-Meier method. The 95% CI was computed using Brookmeyer and Crowley method.

    Measured: Baseline up to withdrawal of consent, loss to follow-up, disease progression, death, or study end (up to approximately 36 months)

  7. Percentage of Participants Who Died During Receiving Second-Line of Treatment

    Percentage of participants who died from any cause during second-line of treatment was reported.

    Measured: 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)

  8. OS During Second-Line of Treatment

    The OS during second-line therapy was defined as the time from the start of second-line therapy (failure of first-line therapy) until death from any cause. Participants alive at the time of analysis and participants who were lost to follow-up were censored at their last clinical assessment date. Median OS during second-line therapy was estimated using Kaplan-Meier method. The 95% CI was computed using Brookmeyer and Crowley method.

    Measured: 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)

  9. Number of Participants Receiving Second-Line Treatment by Treatment Type

    Second-line anti-cancer treatment was initiated after disease progression on first-line therapy. Number of participants who started second-line of treatment by treatment type was reported. Participants who received combination treatment were counted for each treatment type.

    Measured: Baseline up to approximately 35 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Dec 2013 (estimated)
  2. Study start5 Dec 2013
  3. Primary completion4 Nov 2016
  4. Study completion4 Nov 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
50 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02019277
Sponsor's protocol ID
ML28784
Acronym
SAPPHIRE
Status last verified
Sep 2018
First submitted
18 Dec 2013
Last updated
13 Sep 2018

Publications

  • Woodward N, De Boer RH, Redfern A, White M, Young J, Truman M, Beith J. Results From the First Multicenter, Open-label, Phase IIIb Study Investigating the Combination of Pertuzumab With Subcutaneous Trastuzumab and a Taxane in Patients With HER2-positive Metastatic Breast Cancer (SAPPHIRE). Clin Breast Cancer. 2019 Jun;19(3):216-224. doi: 10.1016/j.clbc.2019.02.008. Epub 2019 Feb 27.

    PubMed 30922805

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Docetaxel, Nab-paclitaxel and Paclitaxel in people with Breast Cancer, run by Hoffmann-La Roche at 13 sites in Australia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Jul 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With Adverse Events (AEs) and Serious AEs (time frame: Baseline up to 28 days after last study drug administration (up to 36 months)). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02019277, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Sep 2018.

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