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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)

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ClinicalTrials.gov Identifier: NCT01989676
Recruitment Status : Active, not recruiting
First Posted : November 21, 2013
Results First Posted : January 23, 2018
Last Update Posted : December 5, 2018
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Metastatic Breast Cancer Biological: PF-05280014 Drug: Paclitaxel Biological: Herceptin® Phase 3

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 707 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : February 24, 2014
Actual Primary Completion Date : August 24, 2016
Estimated Study Completion Date : January 18, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: PF-05280014 Biological: PF-05280014
Concentrate for solution for infusion, sterile vial 150 mg. Initial dose of 4 mg/kg over 90 minutes (depending on tolerability) IV infusion, then 2 mg/kg over 30 to 90 minutes (depending on tolerability) IV infusion until disease progression. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the PF-05280014 regimen may be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability.
Other Name: Trastuzumab-Pfizer

Drug: Paclitaxel
A nonaqueous solution intended for dilution with a suitable parenteral fluid prior to intravenous infusion. Paclitaxel is available in 30 mg (5 mL), 100 mg (16.7 mL), and 300 mg (50 mL) multidose vials. Each mL of sterile nonpyrogenic solution contains 6 mg paclitaxel. The starting dose of paclitaxel will be 80 mg/m^2 by IV infusion over 60 minutes (duration of infusion may be modified according to local standard of care, if applicable). Provision is made for dose reduction to 70 mg/m^2 and then 60 mg/m^2 as needed. In the absence of disease progression in the judgment of the investigator or prohibitive toxicity, patients will receive treatment with paclitaxel for at least 6 cycles or until maximal benefit of response is obtained, in the judgment of the investigator.

Active Comparator: Herceptin® Biological: Herceptin®
Concentrate for solution for infusion, sterile vial 150 mg. Initial dose of 4 mg/kg over 90 minutes (depending on tolerability) IV infusion, then 2 mg/kg over 30 to 90 minutes (depending on tolerability) IV infusion weekly until disease progression. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the Herceptin® regimen may be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability.
Other Name: Trastuzumab (EU)

Drug: Paclitaxel
A nonaqueous solution intended for dilution with a suitable parenteral fluid prior to intravenous infusion. Paclitaxel is available in 30 mg (5 mL), 100 mg (16.7 mL), and 300 mg (50 mL) multidose vials. Each mL of sterile nonpyrogenic solution contains 6 mg paclitaxel. The starting dose of paclitaxel will be 80 mg/m^2 by IV infusion over 60 minutes (duration of infusion may be modified according to local standard of care, if applicable). Provision is made for dose reduction to 70 mg/m^2 and then 60 mg/m^2 as needed. In the absence of disease progression in the judgment of the investigator or prohibitive toxicity, patients will receive treatment with paclitaxel for at least 6 cycles or until maximal benefit of response is obtained, in the judgment of the investigator.




Primary Outcome Measures :
  1. 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. ]
    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 :
  1. 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. ]
    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.

  2. 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. ]
    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.

  3. 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. ]
    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.

  4. 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 ]
    Human PK serum samples were analyzed for concentrations of PF-05280014 using a validated, sensitive, and specific enzyme-linked immuno-sorbent assay (ELISA).

  5. 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 ]
    Human PK serum samples were analyzed for concentrations of trastuzumab-EU using a validated, sensitive, and specific ELISA.

  6. 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. ]
    Human PK serum samples were analyzed for concentrations of PF-05280014 using a validated, sensitive, and specific ELISA.

  7. 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. ]
    Human PK serum samples were analyzed for concentrations of trastuzumab-EU using a validated, sensitive, and specific ELISA.

  8. 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. ]
    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.

  9. 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. ]
    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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01989676


  Show 230 Study Locations
Sponsors and Collaborators
Pfizer
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer

Additional Information:
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01989676     History of Changes
Other Study ID Numbers: B3271002
REFLECTIONS B327-02
2013-001352-34 ( EudraCT Number )
B3271002 ( Other Identifier: Alias Study Number )
First Posted: November 21, 2013    Key Record Dates
Results First Posted: January 23, 2018
Last Update Posted: December 5, 2018
Last Verified: November 2018

Keywords provided by Pfizer:
Phase 3
trastuzumab
Breast Neoplasms

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Paclitaxel
Albumin-Bound Paclitaxel
Trastuzumab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action