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

NCT02019277 | Completed Phase 3 Results

• 1 other identifier: ML28784
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 13

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.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (5)

• 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.

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

• 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.

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

• 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.

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

• 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.

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

• 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.

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

Secondary Outcomes (9)

• 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

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

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

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

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

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

• Percentage of Participants Who Died Due to Any Cause

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

• Overall Survival (OS)

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

Study Arms (1)

Trastuzumab SC, Pertuzumab, and Taxane

EXPERIMENTAL

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.

Drug: Docetaxel; Drug: Nab-paclitaxel; Drug: Paclitaxel; Drug: Pertuzumab; Drug: Trastuzumab

Interventions

Docetaxel DRUG

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

Trastuzumab SC, Pertuzumab, and Taxane

Nab-paclitaxel DRUG

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

Trastuzumab SC, Pertuzumab, and Taxane

Paclitaxel DRUG

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

Trastuzumab SC, Pertuzumab, and Taxane

Pertuzumab DRUG

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.

Also known as: Perjeta

Trastuzumab SC, Pertuzumab, and Taxane

Trastuzumab DRUG

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

Also known as: Herceptin

Trastuzumab SC, Pertuzumab, and Taxane

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (13)

St George Hospital; Cancer Care Centre

Kogarah, New South Wales, 2217, Australia

Location

Port Macquarie Base Hospital

Port Macquarie, New South Wales, 2444, Australia

Location

Newcastle Mater Misericordiae Hospital; Oncology

Waratah, New South Wales, 2298, Australia

Location

Mater Hospital; Cancer Services

South Brisbane, Queensland, 4101, Australia

Location

Princess Alexandra Hospital Woolloongabba; Clinical Hematology and Medical Oncology

Woolloongabba, Queensland, 4102, Australia

Location

Lyell McEwin Hospital

Adelaide, South Australia, 5112, Australia

Location

Launceston General Hospital

Launceston, Tasmania, 7250, Australia

Location

Bendigo Hospital; Oncology

Bendigo, Victoria, 3550, Australia

Location

Monash Medical Centre; Oncology

Clayton, Victoria, 3168, Australia

Location

Geelong Hospital; Andrew Love Cancer Centre

Geelong, Victoria, 3220, Australia

Location

Royal Melbourne Hospital; Hematology and Medical Oncology

Parkville, Victoria, 3052, Australia

Location

Fiona Stanley Hospital

Murdoch, Western Australia, 6150, Australia

Location

St John of God Murdoch Hospital; Oncology West

Murdoch, Western Australia, 6150, Australia

Location

Related Publications (1)

• 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.

  PMID: 30922805 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Docetaxel; 130-nm albumin-bound paclitaxel; Paclitaxel; pertuzumab; Trastuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2013
• First Posted: December 24, 2013
• Study Start: December 5, 2013
• Primary Completion: November 4, 2016
• Study Completion: November 4, 2016
• Last Updated: September 13, 2018
• Results First Posted: July 23, 2018

Record last verified: 2018-09

Locations

AU (13)