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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)

NCT01989676

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.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

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

  • Metastatic Breast Cancer

Interventions

DrugSynonymsArms
PF-05280014Trastuzumab-PfizerPF-05280014
PaclitaxelPF-05280014
Herceptin®Trastuzumab (EU)Herceptin®
PaclitaxelHerceptin®

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

NameTypeDescriptionInterventions
PF-05280014Experimental
  • Paclitaxel
Herceptin®Active Comparator
  • Paclitaxel

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 the cutoff date of 24 August 2016 when 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 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 as of the cutoff date of 24 August 2016.
Safety Issue:
Description:One (1)-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. The 95% CI for the median time to event was based on the Brookmeyer and Crowley method. The 95% CI for the hazard ratio was based on the Cox's proportional hazards model.
Measure:Duration of Response (DOR) Per Central Radiology Assessments: ITT Population
Time Frame:From the date of randomization until 378 days post-randomization as of the cutoff date of 24 August 2016.
Safety Issue:
Description:DOR was defined as the time from date of the first documentation of objective tumor response (CR or PR) to the first documentation of PD, or to 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. The 95% CI for the median time to event was based on the Brookmeyer and Crowley method. The 95% CI for the hazard ratio was based on the Cox's proportional hazards model.
Measure:One-year Survival Rate: ITT Population
Time Frame:From the date of randomization until 378 days post-randomization as of the cutoff date of 24 August 2016.
Safety Issue:
Description:One-year survival rate was analyzed based on the time from date of randomization to the date of death due to any cause while the participant was on the study. The 95% CI for the median time to event was based on the Brookmeyer and Crowley method. The 95% CI for the hazard ratio was based on the Cox's proportional hazards model.
Measure:Serum Peak (1 Hour Post End of Infusion) Concentration of PF-05280014 at Selected Cycles: Pharmacokinetics (PK) Population
Time Frame:Available peak PK concentration data collected at Cycle 1, Day 1 and Cycle 5, Day 1 as of the data cutoff date of 24 August 2016
Safety Issue:
Description:Human PK serum samples were analyzed for concentrations of PF-05280014 using a validated, sensitive, and specific enzyme-linked immuno-sorbent assay (ELISA).
Measure:Serum Peak (1 Hour Post End of Infusion) Concentration of Trastuzumab-EU at Selected Cycles: PK Population
Time Frame:Available peak PK concentration data collected at Cycle 1, Day 1 and Cycle 5, Day 1 as of the data cutoff date of 24 August 2016
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:Available trough concentrations collected from Cycle 1, Day 1 to Cycle 17, Day 1 as of the data cutoff date of 24 August 2016, except the EOT visit and unplanned records.
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:Available trough concentrations collected from Cycle 1, Day 1 to Cycle 17, Day 1 as of the data cutoff date of 24 August 2016, except the EOT visit and unplanned records.
Safety Issue:
Description:Human PK serum samples were analyzed for concentrations of trastuzumab-EU using a validated, sensitive, and specific ELISA.
Measure:Anti-Drug Antibodies (ADA) Incidence: Safety Population
Time Frame:Available data from Baseline through Cycle 17, Day 1 as of the data cutoff date of 24 August 2016, except the EOT visit and unplanned records.
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:Neutralizing Antibodies (Nab) Incidence at Cycle 1 Day 1 Prior to Treatment: Safety Population
Time Frame:Available data from Baseline to Cycle 17, Day 1 as of the data cutoff date of 24 August 2016, except the EOT visit and unplanned records.
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. All samples at baseline (prior to treatment) or post-treatment were taken prior to dosing. All participants with the exception of 1 participant in the trastuzumab-EU group tested negative for ADA (titer <1.00) from Cycle 1, Day 1 post-treatment through Cycle 17, Day 1. The corresponding NAb result for this Cycle 17, Day 1 ADA positive sample was not yet available; thus, not reported. 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:Active, not recruiting
Lead Sponsor:Pfizer

Trial Keywords

  • Phase 3
  • trastuzumab
  • Breast Neoplasms

Last Updated

December 21, 2017