DOUBLE-BLIND STUDY OF PF-05280014 PLUS PACLITAXEL VERSUS TRASTUZUMAB PLUS PACLITAXEL FOR THE FIRST-LINE TREATMENT OF PATIENTS WITH HER2-POSITIVE METASTATIC BREAST CANCER

• Register: EUCTR
• Last refreshed on: 31 August 2020
• Main ID: EUCTR2013-001352-34-LV
• Date of registration: 28/11/2014
• Prospective Registration: Yes
• Primary sponsor: Pfizer Inc,
• Public title: DOUBLE-BLIND STUDY OF PF-05280014 PLUS PACLITAXEL VERSUS TRASTUZUMAB PLUS PACLITAXEL FOR THE FIRST-LINE TREATMENT OF PATIENTS WITH HER2-POSITIVE METASTATIC BREAST CANCER
• Scientific title: A PHASE 3 RANDOMIZED, DOUBLE-BLIND STUDY OF PF-05280014 PLUS PACLITAXEL VERSUS TRASTUZUMAB PLUS PACLITAXEL FOR THE FIRST-LINE TREATMENT OF PATIENTS WITH HER2-POSITIVE METASTATIC BREAST CANCER
• Date of first enrolment: 27/03/2015
• Target sample size: 630
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-001352-34
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes; Randomised: yes; Open: no; Single blind: no; Double blind: yes; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: yes; Other specify the comparator: Trastuzumab Plus Paclitaxel; Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Brazil, Chile, Colombia, Czech Republic, Greece, Hungary, India, Japan, Korea, Republic of, Latvia, Mexico, Peru, Philippines, Poland, Portugal, Romania, Serbia, Slovakia, South Africa, Spain, Thailand, Turkey, Ukraine, United States

Contacts

• Name: Clinical Trials.gov Call Centre
• Affiliation: Pfizer Inc

• Name: Clinical Trials.gov Call Centre
• Affiliation: Pfizer Inc

Key inclusion & exclusion criteria

Inclusion criteria:
1. Female patients aged 18 years or older. (Where required by regulations, consent from a legally acceptable representative is required for all patients who are younger than 20 years of age.)
2. Histologically confirmed diagnosis of breast cancer.
3. Presence of metastatic disease.
4. Documentation of HER2 gene amplification or overexpression by one of the following:
a. Gene amplification by fluorescent in-situ hybridization (FISH) or chromogenic in-situ hybridization (CISH) or dual in-situ hybridization (DISH) (as defined by the manufacturer’s kit instruction); OR
b. Overexpression by immunohistochemistry (IHC) categorized as IHC3+; OR
c. Overexpression by immunohistochemistry categorized as IHC2+ with FISH, CISH or DISH confirmation.
Determination of HER2 positive status using one of the Sponsor approved analytical test methods listed in Appendix 1 of the protocol must be documented in the patient’s source documentation.
If HER2 status is unavailable or was determined using a test other than a Sponsor-approved assay, eligibility must be documented prior to randomization either by:
a. The sponsor provided central laboratory OR
b. HER2 local testing using both an IHC and an in-situ hybridization analytical test neither of which are considered Sponsor approved. The results from both assays must be unequivocal (ie, IHC result must be categorized as IHC3+).
5. Available tumor tissue (ie, formalin fixed-paraffin embedded blocks or unstained slides) for central review of HER2 status. Tumor tissue should be from metastatic disease or, if not obtainable, may be from the primary tumor at the time of initial or current diagnosis.
6. Documentation of ER status (positive or negative) based on local laboratory or Sponsor-identified central laboratory.
7. At least 1 measurable lesion as defined by RECIST 1.1, measurable lesions must be outside prior radiation fields. The following kinds of lesions are not measurable according to RECIST 1.1: ascites, pleural or pericardial effusion, osteoblastic or osteolytic bone metastases, and carcinomatous lymphangitis of the lung. The site must forward the radiographs to the independent central review laboratory to obtain confirmation of the presence of measurable disease prior to patient randomization.
8. Eastern Cooperative Oncology Group (ECOG) status of 0 to 2
9. Left ventricular ejection fraction (LVEF) within institutional range of normal, measured by either two dimensional echocardiogram (ECHO) or multigated acquisition (MUGA) scan.
10. Screening laboratory values within the following limits:
a. Absolute neutrophil count (ANC) =1.5 x 109 cells/L (1500/mm3);
b. Platelet count =100 x 109cells/L (100,000/mm3);
c. Hemoglobin =9.0 g/dL (90 g/L);
d. Serum creatinine =1.5 x upper limit of normal (ULN);
e. Total bilirubin =1.5 x ULN (<3 ULN if Gilbert’s disease);
f. Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) =2.5 x ULN (=5 x ULN if liver metastases are present).
11. Recovery (to grade 1 or baseline) from all clinically significant adverse effects of prior therapies (excluding alopecia).
12. Patients of childbearing potential must agree to use 2 highly effective methods of contraception (as described in section 4.4 of the protocol) throughout the study and for 12 months after the last dose of assigned treatment. A patient is of childbearing potential if, in the opinion of the investigator, she is biologically capable of
Exclusion criteria:
1. Patients who are investigational site staff members directly involved in the conduct of the trial and their family members, site staff members otherwise supervised by the Investigator, or patients who are Pfizer employees directly involved in the conduct of the trial.
2. Relapse within 1 year of last dose of previous adjuvant (including neoadjuvant) treatment (except endocrine therapy).
3. Prior systemic therapy for metastatic disease (except endocrine therapy).
4. Prior cumulative dose of doxorubicin of >400 mg/m2, epirubicin dose >800 mg/m2, or the equivalent dose for other anthracyclines or derivatives (e.g., 72 mg/m2 of mitoxantrone). If the patient has received more than one anthracycline, then the cumulative dose must not exceed the equivalent of 400 mg/m2 of doxorubicin.
5. Inflammatory breast cancer.
6. Superficial disease site that cannot be assessed by radiographic method as the only site of measurable disease. Patients with superficial lesions that can be measured by computed tomography (CT) scan or magnetic resonance imaging (MRI) are eligible.
7. Major surgery, radiotherapy, or any investigational agents, within 4 weeks before the administration of the first dose of study treatment.
8. Concurrent administration of other anticancer therapies. Bisphosphonate or Receptor Activator for Nuclear Factor KB (RANK) Ligand inhibition therapy for pre-existing bone metastases or osteoporosis is allowed; prophylactic use to prevent bone metastasis is exclusionary.
9. Active uncontrolled or symptomatic central nervous system (CNS) metastases, as evidenced by clinical symptoms, cerebral edema, and/or progressive growth. Patients with a history of CNS metastases or cord compression are eligible if they have completed definitive treated and have not received anticonvulsants or steroids for at least 4 weeks before first dose of study treatment. Patients with newly detected asymptomatic CNS metastases must complete definitive treatment (e.g., radiotherapy, stereotactic surgery) before being considered for study entry. Patients with a history of carcinomatous meningitis (leptomeningeal disease) are not eligible.
10. Active uncontrolled cardiac disease, including cardiomyopathy, congestive heart failure (CHF) New York Heart Association (NYHA) functional classification of =3, unstable angina, or myocardial infarction within 12 months before first dose of study treatment.
11. Preexisting grade 2 or greater motor or sensory neuropathy.
12. History of severe hypersensitivity reaction to taxanes, trastuzumab, murine proteins, or excipients in their formulations.
13. Clinical contraindication to treatment with steroids preventing use as part of paclitaxel premedication.
14. Pregnant females; breastfeeding females; females of childbearing potential who are unwilling or unable to use 2 highly effective methods of contraception as outlined in this protocol for the duration of the study and for 12 months after last dose of investigational product.
15. Known or demonstrated viral infection as listed below. Testing to demonstrate eligibility is required only in countries where regulations mandate testing. In all other countries, testing should be considered if a patient is at risk for having undiagnosed infection (for example due to history of injection drug use or due to geographic location).
a. Seropositivity for human immunodeficiency virus (HIV);
b. Hepatitis B and/or hepatitis C infection (as detected by positive testi

Age minimum:
Age maximum:
Gender:
Female: yes
Male: no

Health Condition(s) or Problem(s) studied

Metastatic Breast Cancer
MedDRA version: 20.0 Level: LLT Classification code 10027475 Term: Metastatic breast cancer System Organ Class: 100000004864

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: Trastuzumab-Pfizer
Product Code: PF-05280014
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: TRASTUZUMAB
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-

Trade Name: Herceptin®
Product Name: Herceptin®
Product Code: trastuzumab-EU
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: trastuzumab
Current Sponsor code: trastuzumab-EU
Other descriptive name: Herceptin®
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 150-

Primary Outcome(s)

Primary end point(s): Objective Response Rate (ORR), evaluating responses achieved by Week 25 and subsequently confirmed, based on the assessments of the central radiology review in accordance with Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1).

Secondary Objective: •To evaluate the safety of trastuzumab-Pfizer plus paclitaxel versus trastuzumab-EU plus paclitaxel;
•To evaluate secondary measures of tumor control;
•To evaluate the population pharmacokinetics (PK) of trastuzumab-Pfizer and trastuzumab-EU;
•To evaluate the immunogenicity of trastuzumab-Pfizer and trastuzumab-EU.

Main Objective: To compare the objective response rate (ORR) in patients with metastatic HER2-positive breast cancer who receive trastuzumab-Pfizer to those who receive trastuzumab-EU in combination with paclitaxel.

Timepoint(s) of evaluation of this end point: Week 25

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Variable. See Study Flow Charts 1-4, pages 7-14 of the protocol.

Secondary end point(s): • Safety characterized by type, incidence, severity, timing, seriousness, and relationship to study therapy of adverse events and laboratory abnormalities;
• Duration of Response (DOR), One-year progression-free survival (PFS) rate and 1-year survival rate;
• Peak and trough trastuzumab-Pfizer and trastuzumab-EU concentrations at selected cycles;
• Incidence of anti-drug (trastuzumab) antibodies (ADA), including neutralizing antibodies (Nab).

Secondary ID(s)

2013-001352-34-CZ

B3271002

NCT01989676

Source(s) of Monetary Support

Pfizer Inc, 235 East 42nd Street, New York, NY 10017

Ethics review

Status: Approved
Approval date: 26/11/2014
Contact:

Results

• Results available: Yes
• Date Posted: 14/10/2017
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2013-001352-34/results