Clinical trial NCT02019277: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Breast Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2013-12-24
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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 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.


Eligibility criteria: 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

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

Primary outcomes:
measure: Percentage of Participants With Adverse Events (AEs) and Serious AEs
timeFrame: Baseline up to 28 days after last study drug administration (up to 36 months)
measure: Percentage of Participants With AEs by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.0 Intensity Grades
timeFrame: Baseline up to 28 days after last study drug administration (up to 36 months)
measure: Percentage of Participants With AEs Leading to Premature Discontinuation of Investigational Medicinal Products (IMPs)
timeFrame: Baseline up to 28 days after last study drug administration (up to 36 months)
measure: Percentage of Participants With AEs of Suspected Cardiac Origin, by New York Heart Association Classification (NYHA)
timeFrame: Baseline up to 28 days after last study drug administration (up to 36 months)
measure: Percentage of Participants With Left Ventricular Ejection Fraction (LVEF) Below 50%
timeFrame: Baseline up to 28 days after last study drug administration (up to 36 months)
Secondary outcomes:
measure: 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
timeFrame: Baseline up to withdrawal of consent, loss to follow-up, disease progression, death, or study end (up to approximately 36 months)
measure: Percentage of Participants With PD (Assessed According to RECIST Version 1.1) or Death Due to Any Cause
timeFrame: Baseline up to withdrawal of consent, loss to follow-up, disease progression, death, or study end (up to approximately 36 months)
measure: Progression-free Survival (PFS) Assessed According to RECIST Version 1.1
timeFrame: Baseline up to withdrawal of consent, loss to follow-up, disease progression, death, or study end (up to approximately 36 months)
measure: Percentage of Participants Who Died Due to Any Cause
timeFrame: Baseline up to withdrawal of consent, loss to follow-up, disease progression, death, or study end (up to approximately 36 months)
measure: Overall Survival (OS)
timeFrame: Baseline up to withdrawal of consent, loss to follow-up, disease progression, death, or study end (up to approximately 36 months)
measure: Event-free Survival (EFS) Assessed According to RECIST Version 1.1
timeFrame: Baseline up to withdrawal of consent, loss to follow-up, disease progression, death, or study end (up to approximately 36 months)
measure: Percentage of Participants Who Died During Receiving Second-Line of Treatment
timeFrame: 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)
measure: OS During Second-Line of Treatment
timeFrame: 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)
measure: Number of Participants Receiving Second-Line Treatment by Treatment Type
timeFrame: Baseline up to approximately 35 months
Other outcomes:
Locations:
city: Kogarah
country: Australia
facility: St George Hospital; Cancer Care Centre
state: New South Wales
city: Port Macquarie
country: Australia
facility: Port Macquarie Base Hospital
state: New South Wales
city: Waratah
country: Australia
facility: Newcastle Mater Misericordiae Hospital; Oncology
state: New South Wales
city: South Brisbane
country: Australia
facility: Mater Hospital; Cancer Services
state: Queensland
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital Woolloongabba; Clinical Hematology and Medical Oncology
state: Queensland
city: Adelaide
country: Australia
facility: Lyell McEwin Hospital
state: South Australia
city: Launceston
country: Australia
facility: Launceston General Hospital
state: Tasmania
city: Bendigo
country: Australia
facility: Bendigo Hospital; Oncology
state: Victoria
city: Clayton
country: Australia
facility: Monash Medical Centre; Oncology
state: Victoria
city: Geelong
country: Australia
facility: Geelong Hospital; Andrew Love Cancer Centre
state: Victoria
city: Parkville
country: Australia
facility: Royal Melbourne Hospital; Hematology and Medical Oncology
state: Victoria
city: Murdoch
country: Australia
facility: Fiona Stanley Hospital
state: Western Australia
city: Murdoch
country: Australia
facility: St John of God Murdoch Hospital; Oncology West
state: Western Australia
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.