A Study Of PF-05280014 [Trastuzumab-Pfizer] Or Herceptin® [Trastuzumab-EU] Plus Paclitaxel In HER2 Positive First Line Metastatic Breast Cancer Treatment (REFLECTIONS B327-02)
- Conditions
- Metastatic Breast Cancer
- Interventions
- Registration Number
- NCT01989676
- Lead Sponsor
- Pfizer
- Brief Summary
The current study will compare the efficacy, safety, pharmacokinetics and immunogenicity of PF-05280014 in combination with paclitaxel versus trastuzumab sourced from the European Union (trastuzumab-EU) with paclitaxel in female patients with HER2-positive, metastatic breast cancer in the first-line treatment setting. The hypothesis to be tested in this study is that the efficacy (ORR) of PF-05280014 is similar to trastuzumab-EU.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 707
- Histologically confirmed diagnosis of breast cancer.
- Presence of metastatic disease.
- Documentation of HER2 gene amplification or overexpression.
- Available tumor tissue for central review of HER2 status.
- At least 1 measurable lesion as defined by RECIST 1.1.
- Eastern Cooperative Oncology Group status of 0 to 2.
- Left ventricular ejection fraction within institutional range of normal, measured by either two dimensional echocardiogram or multigated acquisition scan.
- Relapse within 1 year of last dose of previous adjuvant (including neoadjuvant) treatment (except endocrine therapy) and within 1 year before randomization.
- Prior systemic therapy for metastatic disease (except endocrine therapy).
- Prior cumulative dose of doxorubicin of >400 mg/m2, epirubicin dose >800 mg/m^2, or the equivalent dose for other anthracyclines or derivatives (eg, 72 mg/m^2 of mitoxantrone). If the patient has received more than one anthracycline, then the cumulative dose must not exceed the equivalent of 400 mg/m^2 of doxorubicin.
- Inflammatory breast cancer.
- Active uncontrolled or symptomatic central nervous system metastases.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description PF-05280014 PF-05280014 - PF-05280014 Paclitaxel - Herceptin® Herceptin® - Herceptin® Paclitaxel -
- Primary Outcome Measures
Name Time Method Objective Response Rate (ORR) Derived From Central Radiology Assessments: ITT Population From the date of randomization until all participants had either completed the Week 33 tumor assessment or discontinued study drug earlier than the Week 33 visit ORR was defined as the percentage of participants who achieved complete response (CR, complete disappearance of all target lesions with the exception of nodal disease; all target nodes must have decreased to normal size \[short axis \<10 mm\]) or partial response (PR, \>=30% decrease from baseline of the sum of diameters (SOD) of all target measurable lesions; the short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions) by Week 25 of the study and confirmed on a follow-up assessment (Week 33+/-14 days), based on the assessments of the central radiology review in accordance with RECIST 1.1.
- Secondary Outcome Measures
Name Time Method Serum Peak Concentration of PF-05280014 at Selected Cycles: Pharmacokinetics (PK) Population 1 hour post end of infusion on Day 1 of Cycles 1 and 5 Human PK serum samples were analyzed for concentrations of PF-05280014 using a validated, sensitive, and specific enzyme-linked immunosorbent assay (ELISA).
Serum Peak Concentration of Trastuzumab-EU at Selected Cycles: PK Population 1 hour post end of infusion on Day 1 of Cycles 1 and 5 Human PK serum samples were analyzed for concentrations of trastuzumab-EU using a validated, sensitive, and specific ELISA.
One-year Progression-Free Survival (PFS) Rate Derived From Central Radiology Assessments: ITT Population From the date of randomization until 378 days post-randomization One-year PFS rate was analyzed based on the time from date of randomization to first documentation of progressive disease (PD), or death due to any cause in the absence of documented PD, based on the assessments of the central radiology review in accordance with RECIST 1.1. PD was defined for target disease as at least a 20% increase in sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum was observed during therapy) with a minimum absolute increase of 5 mm. For non-target disease: PD was defined as unequivocal progression of pre-existing lesions and if overall tumor burden increased sufficiently to merit discontinuation of therapy; appearance of any new unequivocal malignant lesion was also considered PD. The 95% CI for the median time to event was based on the Brookmeyer and Crowley method.
Duration of Response (DOR) Per Central Radiology Assessments: ITT Population From the date of randomization until 378 days post-randomization DOR:time from first documentation of objective response (CR or PR) to first documentation of PD/death due to any cause in absence of documented PD, based on central radiology review. As per RECIST v1.1, CR:complete disappearance of all target lesions with exception of nodal disease; all target nodes reduced in short axis \<10 mm. PR: \>=30% decrease from baseline of SOD of target lesions; short diameter used in sum for target nodes,longest diameter used in sum for other target lesions. PD for target disease:at least 20% increase in SOD of target lesions above smallest sum observed (over baseline if no decrease in sum observed) with minimum absolute increase of 5 mm. For non-target disease:unequivocal progression of pre-existing lesions and if overall tumor burden increased sufficiently to merit discontinuation of therapy; appearance of any new unequivocal malignant lesion was also considered PD. The 95% CI for median time to event was based on the Brookmeyer and Crowley method.
Overall Survival: ITT Population From the date of randomization until end of study (approximately 6 years) Overall survival was analyzed based on the time from date of randomization to the date of death due to any cause. Participants last known to be alive were censored on the date of last contact. The 95% CI for the median time to event was based on the Brookmeyer and Crowley Method.
Serum Trough (Pre-dose) Concentration of PF-05280014 at Selected Cycles: PK Population Pre-dose on Day 1 of Cycles 1, 3, 4, 5, 7, 8, 11, 14, 17 and Day 8 of Cycles 1 and 5 Human PK serum samples were analyzed for concentrations of PF-05280014 using a validated, sensitive, and specific ELISA.
Serum Trough (Pre-dose) Concentration of Trastuzumab-EU at Selected Cycles: PK Population Pre-dose on Day 1 of Cycles 1, 3, 4, 5, 7, 8, 11, 14, 17 and Day 8 of Cycles 1 and 5 Human PK serum samples were analyzed for concentrations of trastuzumab-EU using a validated, sensitive, and specific ELISA.
Number of Participants With Positive Neutralizing Antibodies (Nab) Prior to Treatment: Safety Population Cycle 1 Day 1 (prior to treatment) Human serum samples testing positive for the presence of ADA (anti-PF-05280014 or anti-trastuzumab-EU) were analyzed for the presence or absence of NAb (neutralizing anti-PF-05280014 or neutralizing anti-trastuzumab-EU antibodies) following a tiered approach using screening and titer determination. The number of participants at baseline (prior to treatment) with a positive NAb sample (titer \>=1.48) is provided.
Number of Participants With Positive Anti-Drug Antibodies (ADA) Sample: Safety Population Pre-dose on Day 1 of Cycles 1, 3, 5, 8, 11, 14, 17 Two sensitive, specific, and semi-quantitative electrochemiluminescent (ECL) immunoassays, 1 for detecting antibodies against PF-05280014 and the other for detecting antibodies against trastuzumab, were used to analyze ADA samples. Serum samples were first screened for ADA. Any samples that were positive in the screening assay were further analyzed to confirm the positive result and determine the antibody titers. All samples were taken prior to dosing. The number of participants with a positive sample (titer \>=1.0) is provided.
Trial Locations
- Locations (180)
Cancer Center of Central Connecticut
🇺🇸Southington, Connecticut, United States
Florida Cancer Research Institute
🇺🇸Plantation, Florida, United States
COIBA - Centro de Oncologia e Investigacion Buenos Aires
🇦🇷Berazategui, Buenos Aires, Argentina
Instituto De Oncologia De Rosario
🇦🇷Rosario, Santa FE, Argentina
Centro Medico San Roque
🇦🇷San Miguel de Tucuman, Tucuman, Argentina
Sanatorio de la Providencia
🇦🇷C.a.b.a, Argentina
CRIO - Centro Regional Integrado de Oncologia
🇧🇷Fortaleza, CE, Brazil
Associacao de Combate ao Cancer em Goias - Hospital Araujo Jorge
🇧🇷Goiania, GO, Brazil
Liga Paranaense de Combate ao Cancer - Hospital Erasto Gaertner
🇧🇷Curitiba, Parana, Brazil
Instituto do Cancer de Londrina - Hospital do Cancer de Londrina - HCL
🇧🇷Londrina, Parana, Brazil
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