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A Study of Pertuzumab and Trastuzumab Treatment in Combination With a Taxane in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Metastatic Breast Cancer

This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
Hoffmann-La Roche Identifier:
First received: December 18, 2013
Last updated: October 11, 2016
Last verified: October 2016
This open-label, multicenter, phase IIIb study will assess the safety, tolerability and efficacy of a combination therapy of intravenous (IV) pertuzumab (Perjeta), subcutaneous (SC) trastuzumab (Herceptin), 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 per 5 milliliter [mg/5 mL]). 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. Time on study treatment is up to 2 years.

Condition Intervention Phase
Breast Cancer
Drug: Docetaxel
Drug: Nab-paclitaxel
Drug: Paclitaxel
Drug: Pertuzumab
Drug: Trastuzumab
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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 (SAPPHIRE)

Resource links provided by NLM:

Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percentage of Participants With Adverse Events (AEs), Serious AEs, and AEs Leading to Premature Discontinuation [ Time Frame: Baseline up to 36 months ] [ Designated as safety issue: No ]
  • Percentage of Participants With Cardiac AEs [ Time Frame: Baseline up to 36 months ] [ Designated as safety issue: Yes ]
  • Percentage of Participants with Congestive Heart Failure (CHF), According to NCI CTCAE Version 4.0 and New York Heart Association Classification (NYHA) [ Time Frame: Baseline up to 36 months ] [ Designated as safety issue: Yes ]
  • Percentage of Participants with Asymptomatic Decline in Left Ventricular Ejection Fraction (LVEF), Assessed Using Echocardiography (ECHO) or Multiple-gated Acquisition (MUGA) Scan [ Time Frame: Baseline up to 28 days after last dose (up to 36 months) ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Percentage of Participants with Best Overall Response of Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 [ Time Frame: Baseline up to 36 months ] [ Designated as safety issue: No ]
  • Progression-free Survival Assessed According to RECIST Version 1.1 [ Time Frame: Baseline up to 36 months ] [ Designated as safety issue: No ]
  • Overall Survival [ Time Frame: Baseline up to 36 months ] [ Designated as safety issue: No ]
  • Event-free Survival Assessed According to RECIST Version 1.1 [ Time Frame: Baseline up to 36 months ] [ Designated as safety issue: No ]
  • Percentage of Participants Receiving Second-Line Treatment [ Time Frame: Baseline up to 36 months ] [ Designated as safety issue: No ]

Enrollment: 50
Study Start Date: December 2013
Estimated Study Completion Date: November 2016
Estimated Primary Completion Date: November 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Trastuzumab, 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.
Drug: Docetaxel
Dosing regimen to be determined by the investigator, routine clinical practices.
Drug: Nab-paclitaxel
Dosing regimen to be determined by the investigator, routine clinical practices.
Drug: Paclitaxel
Dosing regimen to be determined by the investigator, routine clinical practices.
Drug: 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 intravenous infusion every 3 weeks.
Other Name: Perjeta
Drug: Trastuzumab
Trastuzumab will be administered at a fixed dose of 600 milligrams (mg) per 5 milliliter (mL) subcutaneously every 3 weeks.
Other Name: Herceptin


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT02019277

Australia, New South Wales
Kogarah, New South Wales, Australia, 2217
Port Macquarie, New South Wales, Australia, 2444
Waratah, New South Wales, Australia, 2298
Australia, Queensland
South Brisbane, Queensland, Australia, 4101
Woolloongabba, Queensland, Australia, 4102
Australia, South Australia
Adelaide, South Australia, Australia, 5112
Australia, Tasmania
Launceston, Tasmania, Australia, 7250
Australia, Victoria
Bendigo, Victoria, Australia, 3550
East Bentleigh, Victoria, Australia, VIC 3165
Geelong, Victoria, Australia, 3220
Parkville, Victoria, Australia, 3052
Australia, Western Australia
Murdoch, Western Australia, Australia, 6150
Sponsors and Collaborators
Hoffmann-La Roche
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche Identifier: NCT02019277     History of Changes
Other Study ID Numbers: ML28784 
Study First Received: December 18, 2013
Last Updated: October 11, 2016
Health Authority: Australia: Therapeutic Goods Administration

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action processed this record on October 25, 2016