Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Breast Neoplasms

Breast Diseases

Skin Diseases

Antineoplastic Agents

All Drugs and Chemicals

Pharmaceutical Solutions

Natriuretic Agents

Trastuzumab

Carboplatin

Docetaxel

Mannitol

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Immunological

Concentrate for solution for infusion, sterile vial 150 mg, Day 1 Cycle 1 will be a loading dose of 8 mg/kg infused over 90 minutes. Subsequent infusions will follow every 3 weeks (i.e., cycled every 21 days) with a dose of 6 mg/kg administered over 30 to 90 minutes depending on tolerability, maximum of 6 cycles.

PF-05280014

Injection concentrate single-dose vials containing 20 mg (0.5 mL) or 80 mg (2 mL), each mL contains 40 mg docetaxel (anhydrous) and 1040 mg polysorbate 80, The starting dose of Taxotere® (docetaxel) will be 75 mg/m2 administered intravenously over 60 minutes every three weeks on Day 1 of each cycle (i.e., every 21 days), maximum 6 cycles.

Taxotere®

Lyophilized powder, single-dose vials containing 50 mg, 150 mg, and 450 mg of Carboplatin for administration by intravenous infusion (each vial contains equal parts by weight of Carboplatin and mannitol), starting dose 6 AUC, over 15 minutes or longer every three weeks on Day 1 of each cycle (i.e., every 21 days), maximum 6 cycles.

Paraplatin®

Concentrate for solution for infusion, sterile vial 150 mg, Day 1 Cycle 1 will be a loading dose of 8 mg/kg infused over 90 minutes. Subsequent infusions will follow every 3 weeks (i.e., cycled every 21 days) with a dose of 6 mg/kg administered over 30 to 90 minutes depending on tolerability, maximum 6 cycles.

Trastuzumab-EU

Pfizer CT.gov Call Center

The current study will compare PK, efficacy, safety, and immunogenicity of PF-05280014 (Trastuzumab-Pfizer) in combination with Taxotere® and Carboplatin (Paraplatin) versus Herceptin® (Trastuzumab-EU) approved in the EU in combination with Taxotere® and Carboplatin (Paraplatin) in patients with operable HER2 positive, breast cancer in the neoadjuvant setting. The hypothesis to be tested in this study is the percentage of patients with steady state Cycle 5 Ctrough (Cycle 6 pre-dose) \>20 µg/mL of trastuzumab-Pfizer is similar to EU-approved trastuzumab, using a margin of -12.5%.

A Study Of PF-05280014 Or Trastuzumab Plus Taxotere® And Carboplatin In HER2 Positive Breast Cancer In The Neoadjuvant Setting (REFLECTIONS B327-04)

A RANDOMIZED, DOUBLE-BLIND PHARMACOKINETIC STUDY OF PF-05280014 PLUS TAXOTERE (REGISTERED) AND CARBOPLATIN VERSUS HERCEPTIN (REGISTERED) PLUS TAXOTERE (REGISTERED) AND CARBOPLATIN FOR THE NEOADJUVANT TREATMENT OF PATIENTS WITH OPERABLE HER2-POSITIVE BREAST CANCER

Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

The percentage of participants with Cycle 5 Ctrough (Cycle 6 pre-dose) \>20 μg/mL in each treatment group, the denominator being the number of participants in the per protocol population for each treatment group.

Samples of blood were taken pre-dose on Cycles 1, 2, 4, 5, and 6, and at 1 hour post dose on Cycles 1 and 5 for pharmacokinetic evaluation.

Following surgery after treatment completion, tumors were assessed as Complete Pathological Response, Partial Pathological Response, or No Pathological Response.

ORR was defined as Complete Response (CR), Partial Response (PR), Stable (SD), Progressive Disease (PD) or Indeterminate (IND). ORR was the percentage of participants who had CR or PR at Cycle 6/End of treatment.

The number of participants with positive (titer \>=1.00) pre-dose ADA samples, participants counted towards the total if for at least one sample, the ADA was positive.

The number of participants with positive (NAb response \>=1.48) pre-dose NAb samples, participants counted towards the total if for at least one sample, the NAb was positive.

Pfizer

Treatment emergent adverse events were defined as any adverse event that occurred or any preexisting adverse event that worsened within the reporting time frame.

Participants received a loading dose of 8 mg/kg of PF-05280014 on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin AUC 6 were administered on Day 1 of each cycle.

Participants received a loading dose of 8 mg/kg of trastuzumab-EU on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin AUC 6 were administered on Day 1 of each cycle.

Total

Age, Continuous

Female

Sex/Gender, Customized

All participants who were randomized into the study.

It was decided that the secondary study objective to explore the relationship between drug exposure and pCR for PF-05280014 versus trastuzumab-EU would not be analyzed.

All participants who were HER2+ and randomized into the study; and who had received 6 cycles of PF-05280014 or trastuzumab-EU treatment; and had no temporary delays of PF-05280014 or trastuzumab-EU treatment lasting more than 1 week; and had no other significant protocol deviations.

Percentage of Participants With Steady State Drug Concentration Ctrough (Cycle 6 Pre-dose) >20 µg/mL at Cycle 5.

Cycle 1/Day 1 0 hours N= 101, 88

Cycle 1/Day 1 1 hour N= 97, 80

Cycle 2/Day 21 0 hours N= 99, 88

Cycle 4/Day 63 0 hours N= 98, 89

Cycle 5/Day 84 0 hours N= 101, 87

Cycle 5/Day 84 1 hour N= 90, 80

Cycle 6/Day 105 0 hours N= 101, 89

All participants who were HER2+ and randomized into the study; and who have received 6 cycles of PF-05280014 or trastuzumab-EU treatment; and had no temporary delays of PF-05280014 or trastuzumab-EU treatment lasting more than 1 week; and had no other significant protocol deviations.

Mean Predose Trastuzumab-Pfizer and Trastuzumab-EU Concentrations at Cycles 1 Through 6.

Pathologic Complete Response (pCR) Defined as the Absence of Invasive Neoplastic Cells in the Breast and Lymph Nodes.

Objective Response Rate (ORR) Defined as the Percentage of Participants Having Complete or Partial Response at End of Treatment, Based on Radiographic Assessments of the Tumor.

Cycle 1 (n=113,112)

Cycle 2 (n=111,112)

Cycle 4 (n=108,109)

Cycle 6 (n=108,108)

All participants who received at least 1 dose of study drug.

Incidence of Anti-trastuzumab Antibodies (ADAs) at Cycles 1 Through 6.

Cycle 2 (n=110,112)

Cycle 4 (n=108,110)

Incidence of Neutralizing Antibodies (NAb) at Cycles 1 Through 6.

Participants received a loading dose of 8 mg/kg of PF-05280014 on Cycle 1 Day 1. Subsequent infusions followed every 3 weeks with a dose of 6 mg/kg. Taxotere 75 mg/m2 and carboplatin area under the concentration versus time curve (AUC) 6 were administered on Day 1 of each cycle.

Study

Treatment

Blood and Lymph Conditions

Rare Diseases

Neutropenia

Agranulocytosis

Leukopenia

Cytopenia

Hematologic Diseases

Leukocyte Disorders

Granulocytopenia

Lenograstim

During each chemotherapy cycle eligible patients receive Neulasta® s.c. post chemotherapy application.

During each chemotherapy cycle eligible patients receive LA-EP2006 s.c. post chemotherapy application.

Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.

LA-EP2006

Neulasta®

Sandoz Biopharmaceutical Clinical Development

The study will assess the efficacy of LA-EP2006 compared to Neulasta® with respect to the mean duration of severe neutropenia during treatment with myelosuppressive chemotherapy in breast cancer patients.

This randomized, double-blind trial compared the proposed biosimilar LA-EP2006 with the reference Neulasta® in women (≥18 years) receiving chemotherapy for breast cancer. Therefore patients were randomized to receive LA-EP2006 (n = 159) or the reference product (n = 157) for ≤6 cycles of (neo)-adjuvant TAC (docetaxel 75mg/m\^2, doxorubicin 50 mg/m\^2, and cyclophosphamide 500mg/m\^2) chemotherapy. The primary end point was the duration of severe neutropenia (DSN) during Cycle 1 (defined as number of consecutive days with absolute neutrophil count \<0.5 × 10\^9/l). The equivalence was confirmed if 95% CIs were within a ±1 day margin. LA-EP2006 was equivalent to the reference product in DSN (difference: 0.07 days; 95% CI \[-0.12, 0.26\]). Further, LA-EP2006 and the reference Neulasta® showed no clinically meaningful differences regarding efficacy and safety.

Phase III Study Comparing the Efficacy and Safety of LA-EP2006 and Neulasta®

A Randomized, Double-blind, Parallel-group, Multi-center Phase 3 Comparative Study Investigating Efficacy and Safety of LA-EP2006 and Neulasta® in Breast Cancer Patients Treated With Myelosuppressive Chemotherapy

Mean duration of severe neutropenia, defined as number of consecutive days with ANC \<0.5 × 10\^9 cells/L (grade 4 neutropenia).

FN was defined as an oral temperature ≥ 38.3°C while having an absolute neutrophil count (ANC) \< 0.5 × 10\^9 cells/L. Serious treatment-emergent adverse events (TEAEs) were reconciled with the fever and ANC results recorded in the patient diary and CRF and therefore only the serious TEAEs of FN ("febrile neutropenia", "neutropenic sepsis") were taken into account.

Fever was defined as an oral temperature ≥ 38.3°C. Fever episodes were characterized by maximum oral temperature and the number of patients who had fever at least once.

The depth of ANC nadir was defined as the patient's lowest ANC (10\^9 cells/L) in Cycle 1. Only the evaluable patients with a depth of ANC in Cycle 1 are given.

Numbers of patients with ANC nadir based per day during Cycle 1 are given.

Time to absolute neutrophil count (ANC) recovery in Cycle 1 was defined as the time in days from ANC nadir until the patient's ANC had increased to ≥ 2 × 10\^9 cells/L. Only the evaluable patients with a depth of ANC in Cycle 1 and a later increase of ANC ≥ 2 × 10\^9 cells/L are given.

The number of patients with infections was recorded for each cycle and across all cycles. Infections were identified by the AE documentation page selecting all events coded with System Organ Class "Infections and Infestations".

Number of patients with death due to infections

Sandoz GmbH

Sandoz

If not otherwise specified, only treatment-emergent adverse event (TEAEs) (i.e. AEs with a date of onset on or after the date of the first administration of chemotherapy and not later than 30 days after the last dose of chemotherapy) and post-TEAEs (i.e. AEs with a date of onset after the time point of 30 days after the last chemotherapy administration) are reported. SAF set = safety analysis set was used

During each chemotherapy cycle eligible patients receive LA-EP2006 s.c. post chemotherapy application.

LA-EP2006: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.

During each chemotherapy cycle eligible patients receive Neulasta® s.c. post chemotherapy application.

Neulasta®: Eligible patients are scheduled to receive six cycles of chemotherapy every three weeks. During each chemotherapy cycle pegfilgrastim is injected s.c. post chemotherapy application.

Sex: Female, Male

Ethnicity (NIH/OMB)

More than one race patients (n = 6) were of Mestizo or Parda origin.

Race (NIH/OMB)

BMI is missing for 1 patient allocated to Neulasta®

For 4 patients in the LA-EP2006 treatment group, time since initial diagnosis was \> 12 months. It was confirmed by the respective study site that the patients had not received treatment between diagnosis and study entry.

For 6 patients in the LA-EP2006 treatment group and 10 patients in the Neulasta® treatment group, the date of initial diagnosis was incomplete.

Time since diagnosis

TNM Disease stage was defined according to the American Joint Committee on Cancer (AJCC): (I) = T1 N0 M0 / T0 N1mi M0 / T1 N1mi M0; (II) = T0 N1 M0 / T1 N1 M0 / T2 N0 M0 / T2 N1 M0 / T3 N0 M0; (III) = T0 N2 M0 / T1 N2 M0 / T2 N2 M0 / T3 N1 M0 / T3 N2 M0 / T4 N0 M0 / T4 N1 M0 / T4 N2 M0 / AnyT N3 M0; (IV) = AnyT AnyN M1; T: size or direct extent of the primary tumour; N: degree of spread to regional lymph nodes; N1mi: Micrometastases (\> 0.2 mm and/or \> 200 cells, but none \> 2.0 mm); M: presence of distant; https://www.cancer.gov/types/breast/hp/breast-treatment-pdq#link/_27

Disease stage

Previous breast cancer surgery

Previous radiotherapy

0 (fully active)

1 (restricted in physically strenuous activity)

ECOG = Eastern Cooperative Oncology Group

ECOG performance status

Strategic Planning, Biopharmaceutical Clinical Development

The hierarchical test procedure aimed to show that

1. LA-EP2006 and Neulasta® are equivalent with respect to DSN duration in Cycle 1 (margin±1 day), and, if so
2. LA-EP2006 is non-inferior to Neulasta® with respect to DSN duration in Cycle 1 (margin of -0.6 days).

FAS set = full analysis set; PP set = per protocol set

Mean Duration of Severe Neutropenia (DSN) During Cycle 1 of Chemotherapy

Cycle 1

Cycle 2

Cycle 3

Cycle 4

Cycle 5

Cycle 6

All cycles (at least on incidence)

Number of patients with at least one episode of febrile neutropenia by cycle and across all cycles (FAS set)

Incidence of Febrile Neutropenia (FN)

Overall

Patients with more than 1 event during the study (overall) are counted only once. FAS set = full analysis set

Number of Patients With at Least One Episode of Fever by Cycle and Across All Cycles

Depth of ANC Nadir in Cycle 1

Days 1-5

Day 6

Day 7

Day 8

Day 9

Days 10-15

Number of Patients With ANC Nadir Per Day in Cycle 1

Time to ANC Recovery in Days in Cycle 1

Frequency of Infections by Cycle and Across All Cycles

Mortality Due to Infection

Overall Study

Immune System Diseases

Heart and Blood Diseases

Lymphoma

Multiple Myeloma

Neoplasms, Plasma Cell

Hodgkin Disease

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hemorrhagic Disorders

Lymphosarcoma

Hodgkin Lymphoma

Adjuvants, Immunologic

Immunologic Factors

All consecutive patients, treated for lymphoma or myeloma, which underwent autologous stem cell transplantation in the University Hospital of Brest. All these patients were treated with biosimilars of Filgrastim: Zarzio®.

Daily subcutaneous injection of Zarxio post ASCT, from day 5 until bone marrow recovery (neutrophils \>1 giga/l)

Filgrastim Prefilled Syringe [Zarzio®]

IANOTTO Jean-Christophe, MD, PhD

There are limited data concerning the use of biosimilars of filgrastim in autologous stem cell transplantation (ASCT). This study aimed to evaluate G-CSF efficiency and safety (based on haemograms, transfusion needs and complications) of two biosimilars (Zarzio and Ratiograstim®) compared to those of Neupogen® for our patients who underwent ASCT.

Since 2008, Investigator collected data of all patients who underwent ASCT to treat lymphoma or myeloma.

All the patients signed an institutional informed consent form before the harvest of peripheric stem cells (PROMISE program). Patients received Neupogen® (Amgen-SA) between April 2008 and February 2010, and the next group of patients was treated with Ratiograstim® (Ratiopharm GmbH) until May 2012. The last group of patients received Zarzio® (Sandoz GmbH) until November 2014.

Investigator studied the impact of the Zarzio® use on biological parameters of the bone marrow recovery, transfusion needs and infectious complications. These parameters were then compared to those of the previous patients which were treated with the two other drugs.

The patients were recruited in the University Hospital of Brest. They were consecutive patients, treated by ASCT for their high risk lymphoma and myeloma but without selection.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study Of PF-05280014 Or Trastuzumab Plus Taxotere® And Carboplatin In HER2 Positive Breast Cancer In The Neoadjuvant Setting (REFLECTIONS B327-04)	NCT02187744	Early Breast Ca...	PF-05280014 Taxotere® Paraplatin® Trastuzumab-EU Taxotere® Paraplatin®	18 Years -	Pfizer
Phase III Study Comparing the Efficacy and Safety of LA-EP2006 and Neulasta®	NCT01735175	Neutropenic Com... Breast Neoplasm... Chemotherapy-in... Chemotherapeuti...	LA-EP2006 Neulasta®	18 Years -	Sandoz
Use of Zarzio® in Post-autologous Stem Cell Transplantation Procedure	NCT03323541	Multiple Myelom... Non-hodgkin Lym... Hodgkin Lymphom...	Filgrastim Pref...	18 Years -	University Hospital, Brest
Phase III Study Comparing the Efficacy and Safety of LA-EP2006 and Neulasta®	NCT01735175	Neutropenic Com... Breast Neoplasm... Chemotherapy-in... Chemotherapeuti...	LA-EP2006 Neulasta®	18 Years -	Sandoz
Safety of Anti-tumor Necrosis Factor (TNF) Monoclonal Antibodies in Inflammatory Bowel Disease	NCT02066272	Inflammatory Bo... Ulcerative Coli... Crohn's Disease Indeterminate C...		-	Maria Sklodowska-Curie National Research Institute of Oncology
A Comparative Study Between ABP 501 and Humira® in Participants With Moderate to Severe Plaque Psoriasis	NCT05073315	Plaque Psoriasi...	Adalimumab ABP 501	18 Years - 75 Years	Amgen
A Comparative Study Between ABP 501 and Humira® in Participants With Moderate to Severe Plaque Psoriasis	NCT05073315	Plaque Psoriasi...	Adalimumab ABP 501	18 Years - 75 Years	Amgen
A Study Of PF-05280014 Or Trastuzumab Plus Taxotere® And Carboplatin In HER2 Positive Breast Cancer In The Neoadjuvant Setting (REFLECTIONS B327-04)	NCT02187744	Early Breast Ca...	PF-05280014 Taxotere® Paraplatin® Trastuzumab-EU Taxotere® Paraplatin®	18 Years -	Pfizer
Phase III Study Comparing the Efficacy and Safety of LA-EP2006 and Neulasta®	NCT01735175	Neutropenic Com... Breast Neoplasm... Chemotherapy-in... Chemotherapeuti...	LA-EP2006 Neulasta®	18 Years -	Sandoz
Phase III Study Comparing the Efficacy and Safety of LA-EP2006 and Neulasta®	NCT01735175	Neutropenic Com... Breast Neoplasm... Chemotherapy-in... Chemotherapeuti...	LA-EP2006 Neulasta®	18 Years -	Sandoz
Safety of Anti-tumor Necrosis Factor (TNF) Monoclonal Antibodies in Inflammatory Bowel Disease	NCT02066272	Inflammatory Bo... Ulcerative Coli... Crohn's Disease Indeterminate C...		-	Maria Sklodowska-Curie National Research Institute of Oncology

Spots Global Cancer Trial Database for biosimilars

Every month we try and update this database with for biosimilars cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for biosimilars

Every month we try and update this database with for biosimilars cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for biosimilars cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.