Description:
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.
Title
- Brief Title: 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)
- Official 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
Clinical Trial IDs
- ORG STUDY ID:
B3271002
- SECONDARY ID:
REFLECTIONS B327-02
- SECONDARY ID:
2013-001352-34
- SECONDARY ID:
B3271002
- NCT ID:
NCT01989676
Conditions
Interventions
| Drug | Synonyms | Arms |
|---|
| PF-05280014 | Trastuzumab-Pfizer | PF-05280014 |
| Paclitaxel | | PF-05280014 |
| Herceptin® | Trastuzumab (EU) | Herceptin® |
| Paclitaxel | | Herceptin® |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| PF-05280014 | Experimental | | |
| Herceptin® | Active Comparator | | |
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | Female |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Objective Response Rate (ORR) Derived From Central Radiology Assessments: ITT Population |
| Time Frame: | 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 |
| Safety Issue: | |
| Description: | 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
| Measure: | One-year Progression-Free Survival (PFS) Rate Derived From Central Radiology Assessments: ITT Population |
| Time Frame: | From the date of randomization until 378 days post-randomization |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Duration of Response (DOR) Per Central Radiology Assessments: ITT Population |
| Time Frame: | From the date of randomization until 378 days post-randomization |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Overall Survival: ITT Population |
| Time Frame: | From the date of randomization until end of study (approximately 6 years) |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Serum Peak Concentration of PF-05280014 at Selected Cycles: Pharmacokinetics (PK) Population |
| Time Frame: | 1 hour post end of infusion on Day 1 of Cycles 1 and 5 |
| Safety Issue: | |
| Description: | Human PK serum samples were analyzed for concentrations of PF-05280014 using a validated, sensitive, and specific enzyme-linked immunosorbent assay (ELISA). |
| Measure: | Serum Peak Concentration of Trastuzumab-EU at Selected Cycles: PK Population |
| Time Frame: | 1 hour post end of infusion on Day 1 of Cycles 1 and 5 |
| Safety Issue: | |
| Description: | Human PK serum samples were analyzed for concentrations of trastuzumab-EU using a validated, sensitive, and specific ELISA. |
| Measure: | Serum Trough (Pre-dose) Concentration of PF-05280014 at Selected Cycles: PK Population |
| Time Frame: | Pre-dose on Day 1 of Cycles 1, 3, 4, 5, 7, 8, 11, 14, 17 and Day 8 of Cycles 1 and 5 |
| Safety Issue: | |
| Description: | Human PK serum samples were analyzed for concentrations of PF-05280014 using a validated, sensitive, and specific ELISA. |
| Measure: | Serum Trough (Pre-dose) Concentration of Trastuzumab-EU at Selected Cycles: PK Population |
| Time Frame: | Pre-dose on Day 1 of Cycles 1, 3, 4, 5, 7, 8, 11, 14, 17 and Day 8 of Cycles 1 and 5 |
| Safety Issue: | |
| Description: | Human PK serum samples were analyzed for concentrations of trastuzumab-EU using a validated, sensitive, and specific ELISA. |
| Measure: | Number of Participants With Positive Anti-Drug Antibodies (ADA) Sample: Safety Population |
| Time Frame: | Pre-dose on Day 1 of Cycles 1, 3, 5, 8, 11, 14, 17 |
| Safety Issue: | |
| Description: | 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. |
| Measure: | Number of Participants With Positive Neutralizing Antibodies (Nab) Prior to Treatment: Safety Population |
| Time Frame: | Cycle 1 Day 1 (prior to treatment) |
| Safety Issue: | |
| Description: | 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. |
Details
| Phase: | Phase 3 |
| Primary Purpose: | Interventional |
| Overall Status: | Completed |
| Lead Sponsor: | Pfizer |
Trial Keywords
- Phase 3
- trastuzumab
- Breast Neoplasms
Last Updated
July 6, 2021
