A Study to Evaluate the Efficacy and Safety of Pertuzumab + Trastuzumab + Docetaxel Versus Placebo + Trastuzumab + Docetaxel in Previously Untreated Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Metastatic Breast Cancer

NCT02896855 | Completed Phase 3 Results FDA Drug

• 1 other identifier: YO29296
• Study Type: interventional
• Target: 243
• Locations: 1 country
• Sites: 15

Brief Summary

This Phase III, randomized, double-blind, placebo-controlled, multicenter clinical trial in China will evaluate the efficacy and safety of pertuzumab + trastuzumab + docetaxel compared with placebo + trastuzumab + docetaxel in participants with previously untreated HER2-positive metastatic breast cancer.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Progression-Free Survival, as Determined by the Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

  Progression-free survival (PFS) was defined as the time from randomization to first occurrence of progressive disease (PD), as determined by the investigator using RECIST v1.1, or death from any cause within 18 weeks after the last tumor assessment, whichever occurred first. As per RECIST v1.1, PD is defined as a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 millimeters (mm), and the appearance of new lesions. The Kaplan-Meier approach was used to estimate median PFS for each treatment arm. Data for participants who did not have a PFS event were censored at the time of the last tumor assessment (if no tumor assessments performed after baseline, at randomization plus 1 day).

  From date of randomization until date of PFS event (Median [range] time on study for Arm A vs. Arm B at Primary analysis: 57.14 [3.3-93.3] weeks vs. 59.64 [0.9-90.4] weeks; Final analysis: 145.29 [3.3-225.3] weeks vs. 174.79 [0.9-226.1] weeks)

• Kaplan-Meier Estimate of the Percentage of Participants Event-Free for Progression-Free Survival at 1 to 3 Years, as Determined by the Investigator Using RECIST v1.1

  Progression-free survival (PFS) was defined as the time from randomization to first occurrence of progressive disease (PD), as determined by the investigator using RECIST v1.1, or death from any cause within 18 weeks after the last tumor assessment, whichever occurred first. As per RECIST v1.1, PD is a 20% increase in the sum of the diameters of target lesions, an increase in size of measurable lesions by at least 5 mm, and the appearance of new lesions. The Kaplan-Meier approach was used to estimate the percentage of participants who were event-free for PFS at 1, 2, and 3 years. Data for participants who did not have a PFS event were censored at the time of the last tumor assessment (if no tumor assessments performed after baseline visit, at randomization plus 1 day). At final analysis, the median \[range\] time on study for Arm A vs. Arm B was 145.29 \[3.3-225.3\] weeks vs. 174.79 \[0.9-226.1\] weeks.

  At 1, 2, and 3 years

Secondary Outcomes (11)

• Overall Survival

  From date of randomization until the date of death from any cause (Median [range] time on study for Arm A vs. Arm B at Final analysis: 145.29 [3.3-225.3] weeks vs. 174.79 [0.9-226.1] weeks)

• Kaplan-Meier Estimate of the Percentage of Participants Event-Free for Overall Survival at 1 to 3 Years

  At 1, 2, and 3 Years

• Percentage of Participants With Measurable Disease at Baseline Who Achieved an Objective Response (Complete or Partial Response), as Determined by the Investigator Using RECIST v1.1

  At Baseline and every 9 weeks from date of randomization until disease progression or death, whichever occurs first (Median [range] time on study for Arm A vs. Arm B at Primary analysis: 57.14 [3.3-93.3] weeks vs. 59.64 [0.9-90.4] weeks)

• Duration of Objective Response, as Determined by the Investigator Using RECIST v1.1

  From date of first occurrence of documented objective response to date of event (Median [range] time on study for Arm A vs. Arm B at Primary analysis: 57.14 [3.3-93.3] weeks vs. 59.64 [0.9-90.4] weeks)

• Number of Participants With at Least One Adverse Event

  From first dose of study drug until 42 days after last dose of study drug (up to 4 years, 4 months)

Study Arms (2)

Arm A: Placebo + Trastuzumab + Docetaxel

ACTIVE COMPARATOR

Placebo matched to pertuzumab, trastuzumab (8-milligrams per kilogram \[mg/kg\] loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-milligrams per square meter \[mg/m\^2\]) were administered by intravenous (IV) infusion every 3 weeks until disease progression or unacceptable toxicity.

Drug: Docetaxel; Drug: Placebo; Drug: Trastuzumab

Arm B: Pertuzumab + Trastuzumab + Docetaxel

EXPERIMENTAL

Pertuzumab (840-mg loading dose for Cycle 1, followed by 420 mg for subsequent cycles), trastuzumab (8-mg/kg loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles), and docetaxel (75-mg/m\^2) were administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity.

Drug: Docetaxel; Drug: Pertuzumab; Drug: Trastuzumab

Interventions

Docetaxel DRUG

Docetaxel (75-mg/m\^2) was administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity.

Arm A: Placebo + Trastuzumab + Docetaxel; Arm B: Pertuzumab + Trastuzumab + Docetaxel

Pertuzumab DRUG

Pertuzumab (840-mg loading dose for Cycle 1, followed by 420 mg for subsequent cycles) was administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity.

Also known as: Perjeta

Arm B: Pertuzumab + Trastuzumab + Docetaxel

Placebo DRUG

Placebo matched to pertuzumab was administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity.

Arm A: Placebo + Trastuzumab + Docetaxel

Trastuzumab DRUG

Trastuzumab (8-mg/kg loading dose for Cycle 1, followed by 6 mg/kg for subsequent cycles) was administered by IV infusion every 3 weeks until disease progression or unacceptable toxicity.

Also known as: Herceptin

Arm A: Placebo + Trastuzumab + Docetaxel; Arm B: Pertuzumab + Trastuzumab + Docetaxel

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed adenocarcinoma of the breast with locally recurrent or metastatic disease that is suitable for chemotherapy
• HER2-positive metastatic breast cancer (MBC)
• Left ventricular ejection fraction (LVEF) greater than or equal to (\>=) 55 percent (%) at baseline (within 42 days of randomization)
• Eastern Cooperative Oncology Group Performance Status of 0 or 1
• Women of childbearing potential and men should agree to use an effective form of contraception and to continue its use for the duration of study treatment and for at least 7 months after the last dose of study treatment (trastuzumab and/or pertuzumab)

You may not qualify if:

• History of anti-cancer therapy for MBC (with the exception of one prior hormonal regimen for MBC)
• History of approved or investigative tyrosine kinase/HER inhibitors for breast cancer in any treatment setting, except trastuzumab used in the neoadjuvant or adjuvant setting
• History of systemic breast cancer treatment in the neo-adjuvant or adjuvant setting with a disease-free interval from completion of the systemic treatment (excluding hormonal therapy) to metastatic diagnosis of less than (\<) 12 months
• History of persistent Grade \>= 2 hematologic toxicity resulting from previous adjuvant therapy
• Grade \>= 3 peripheral neuropathy at randomization
• History of other malignancy within the last 5 years, except for carcinoma in situ of the cervix or non-melanoma skin carcinoma that has been previously treated with curative intent
• Current clinical or radiographic evidence of central nervous system (CNS) metastases
• History of exposure to cumulative doses of anthracyclines
• Current uncontrolled hypertension or unstable angina
• History of congestive heart failure (CHF) of any New York Heart Association (NYHA) classification, or serious cardiac arrhythmia requiring treatment
• History of myocardial infarction within 6 months of randomization
• History of LVEF decrease to \< 50% during or after prior trastuzumab neo-adjuvant or adjuvant therapy
• Current dyspnea at rest due to complications of advanced malignancy, or other diseases that require continuous oxygen therapy
• Inadequate organ function within 28 days prior to randomization
• Current severe, uncontrolled systemic disease

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (15)

CHINESE ACADEMY OF MEDICAL SCIENCE; CANCER INST. & HOSPITAL; Medical ward

Beijing, 100021, China

Location

Beijing Cancer Hospital

Beijing, 100142, China

Location

Chinese PLA General Hospital

Beijing, 100853, China

Location

the First Hospital of Jilin University

Changchun, 130021, China

Location

Changzhou First People's Hospital

Changzhou, 213003, China

Location

West China Hospital, Sichuan University

Chengdu, 610041, China

Location

The 900th Hospital of PLA joint service support force

Fuzhou, 110016, China

Location

Guangdong General Hospital

Guangzhou, 510080, China

Location

Harbin Medical University Cancer Hospital

Harbin, 150081, China

Location

Jiangsu province hospital; surgery on galactophore

Nanjing, 210029, China

Location

Jiangsu Cancer Hospital

Nanjing, 211100, China

Location

Fudan University Shanghai Cancer Center

Shanghai, 200120, China

Location

First Hospital of China Medical University

Shenyang, 110001, China

Location

Liaoning cancer Hospital & Institute

Shenyang, 110042, China

Location

Zhejiang Cancer Hospital

Zhejiang, 310022, China

Location

Related Publications (1)

• Xu B, Li W, Zhang Q, Shao Z, Li Q, Wang X, Li H, Sun T, Yin Y, Zheng H, Feng J, Zhang H, Lei G, Restuccia E. Pertuzumab, trastuzumab, and docetaxel for Chinese patients with previously untreated HER2-positive locally recurrent or metastatic breast cancer (PUFFIN): a phase III, randomized, double-blind, placebo-controlled study. Breast Cancer Res Treat. 2020 Aug;182(3):689-697. doi: 10.1007/s10549-020-05728-w. Epub 2020 Jun 20.

  PMID: 32564260 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Docetaxel; 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: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 7, 2016
• First Posted: September 12, 2016
• Study Start: September 13, 2016
• Primary Completion: June 27, 2018
• Study Completion: January 22, 2021
• Last Updated: December 16, 2021
• Results First Posted: July 10, 2019

Record last verified: 2021-11

Locations

CN (15)