Breast Cancer
Conditions
Keywords
Breast Carcinoma, Breast neoplasms, Breast Tumors, Cancer of Breast, Anti-Drug Antibodies (ADA), Immunogenicity
Brief summary
The purpose of this study is to compare the immunogenicity of Peg-filgrastim versus Neulasta® as an adjunct to chemotherapy in patients with breast cancer
Detailed description
An open-label, randomized, comparative, parallel group study to assess the Immunogenicity of Lupin's Peg-filgrastim versus Neulasta® as an Adjunct to Chemotherapy in Patients with Breast Cancer Primary Objective: To assess the immunogenicity of Lupin's Peg-filgrastim with Neulasta® in patients with breast cancer. Secondary Objectives: To assess the safety of Lupin's Peg-filgrastim with Neulasta® in patients with breast cancer
Interventions
DRUGLupin's Pegfilgrastim
Administration of Pegfilgrastim
DRUGNeulasta®
Administration of Neulasta®
Sponsors
Lupin Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients must be able and willing to give written informed consent prior to any study related procedures 2. Ambulatory, female patients with an age ≥ 18 years 3. Patients with histologically or cytologically proven diagnosis of breast cancer who are eligible for neoadjuvant or adjuvant chemotherapy. 4. Patients who are planned and eligible to receive/ receiving myelosuppressive chemotherapy regimen that contains at least one chemotherapeutic agent from docetaxel/ paclitaxel / doxorubicin/ cyclophosphamide/ epirubicin 5. Patients who have not received any hematopoietic growth factors (e.g. G-CSF, PegGCSF, erythropoietin) or cytokines (e.g. interleukins, interferons) anytime in the past 6. Patients with baseline WBC ≥ LLN/ 3.5 x 109/L, ANC of ≥ 1.5 x 109/L, platelet count ≥ 100 x 109/L and hemoglobin ≥ 8.5 g/dL 7. Patients with ECOG Performance status of ≤ 2 8. Patient who have estimated life expectancy of more than six months 9. No evidences of hemorrhage
Exclusion criteria
1 Male patients 2\. Hypersensitivity to any of the study drugs or its components like E.coli proteins or similar product 3\. Patients weighing \<45 Kg 4\. Patients with myeloid malignancies and myelodysplasia or evidence of metastatic disease in bone marrow or brain 5\. Patients currently receiving radiation therapy or have completed radiation therapy within 4 weeks before study entry or likely to receive radiotherapy during the study 6\. Patients with prior bone marrow or stem cell transplantation 7\. Patients with chronic use of oral corticosteroids (Except ≤ 20 mg/day dose of prednisolone/ equivalent steroids), immunotherapy, monoclonal antibody therapy and/or biological therapy or use of any other pegylated drug. 8\. Patients with history of systemic antibiotic use within 72 hours prior to chemotherapy 9\. Patients with any active infection which may require systemic antimicrobial therapy. Patients with inadequate hepatic and renal function \[defined as Alkaline Phosphatase \> 2.5 X Upper limits of normal (ULN), serum SGOT \> 2.5 X ULN, SGPT \> 2.5 X ULN, Total bilirubin \> 1.5 X ULN and Creatinine \> 1.5 X ULN of the reference range at the screening assessment\] 10\. Patients with seropositivity for HIV or HBV or HCV 11\. Known cases of Sickle Cell Anemia 12\. Patients with radiographic evidence of active pulmonary infections and/or recent history of pneumonia within 1 month of screening 13\. Patients with clinically evident splenomegaly confirmed subsequently by ultrasonography 14\. Patients with any other clinically significant disease(s) which, in the opinion of the investigator, could compromise the patient's involvement in the study or overall interpretation of the data. \[for e.g. uncontrolled hematologic, renal, hepatic, endocrine, neurologic, psychiatric, metabolic, pulmonary, cardiovascular disease/impaired functioning or history of any autoimmune disease\] 15\. Patients who have participated in another therapeutic clinical study within the past 30 days prior to screening, or are likely to simultaneously participate in another therapeutic clinical study 16\. Patients who are doubtful to comply with study procedures for mental, psychological or social reasons. 17\. Women of child-bearing potential who are not willing to follow a reliable & effective contraceptive measure during the course of the study & at least 3 months after the last dose of study drug. 18\. Pregnant and Breast feeding women.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Comparison of Cumulative Incidence of Anti-pegfilgrastim Antibodies (Binding and Neutralizing) to Pegfilgrastim Between Treatment Groups at the End of Cycle 4 (Day 84). | End of cycle 4, Day 84 | The difference in cumulative incidence of anti-pegfilgrastim antibodies (binding and neutralizing) (measured as difference in proportion of patients with antibodies) to Pegfilgrastim between study groups at the end of cycle 4 will be calculated. Those samples confirmed to be positive for binding antibodies were analyzed for presence of neutralizing antibodies to Pegfilgrastim. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Comparison of Cumulative Incidence of Anti-peg Antibodies (Binding and Neutralizing) Between Treatment Groups at the End of Cycle 4 (Day 84). | Day 84. | The presence of anti-peg antibodies (binding) (measured as difference in proportion of patients with antibodies) between treatment groups at the end of cycle 4 (Day 84) were compared and analysis for the ITT population |
| Comparison of Incidence of Anti-pegfilgrastim Antibodies (Binding & Neutralizing) to Pegfilgrastim Between Treatment Groups on Day 10, Day 21, Day 42, Day 63 and Day 84 | Assessment at each study visit on Day 10, Day 21, Day 42, Day 63, Day 84 | Comparison of incidence of anti-pegfilgrastim antibodies (binding & neutralizing) (measured as difference in proportion of patients with antibodies) to pegfilgrastim between treatment groups on Day 10, Day 21, Day 42, Day 63, Day 84. Analysis population : ITT |
| Secondary Immunogenicity Endpoint | Day 10, Day 21, Day 42, Day 63 and Day 84. | Comparison of incidence of anti-peg antibodies (binding & neutralizing) (measured as difference in proportion of patients with antibodies) between treatment groups on Day 10, Day 21, Day 42, Day 63 and Day 84. Analysis population: ITT population |
Countries
India
Participant flow
Recruitment details
The treatment group (Lupin pegfilgrastim or Neulasta®) for each patient during the study was determined according to the study randomization list. The treatment was assigned at the time of randomization, after confirming the patient's eligibility. Patients were randomized in a 1:1 ratio to receive either Lupin pegfilgrastim or Neulasta®.
Pre-assignment details
All enrolled population included all screened patients who signed the informed consent. The randomized population included all randomized patients irrespective of whether patient received any study drug.
Participants by arm
| Arm | Count |
|---|---|
| Lupin's Pegfilgrastim 6 mg, subcutaneous injection on day 2 or 3 of each 21 ± 3 day cycle. Number of cycles: 4.
Lupin's Pegfilgrastim: Administration of Pegfilgrastim | 70 |
| Neulasta® 6 mg, subcutaneous injection on day 2 or 3 of each 21 ± 3 day cycle. Number of cycles: 4.
Neulasta®: Administration of Neulasta® | 68 |
| Total | 138 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Patient not coming or schedule visit | 1 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 2 |
Baseline characteristics
| Characteristic | Lupin's Pegfilgrastim | Total | Neulasta® |
|---|---|---|---|
| Age, Continuous | 53.6 years STANDARD_DEVIATION 11.59 | 51.2 years STANDARD_DEVIATION 10.52 | 48.8 years STANDARD_DEVIATION 8.73 |
| ECOG Status at Screening Grade 0 | 20 Participants | 36 Participants | 16 Participants |
| ECOG Status at Screening Grade 1 | 50 Participants | 102 Participants | 52 Participants |
| ECOG Status at Screening Grade 2 | 0 Participants | 0 Participants | 0 Participants |
| ECOG Status at Screening Grade 3 | 0 Participants | 0 Participants | 0 Participants |
| ECOG Status at Screening Grade 4 | 0 Participants | 0 Participants | 0 Participants |
| ECOG Status at Screening Grade 5 | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 70 Participants | 138 Participants | 68 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 70 Participants | 138 Participants | 68 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment India | 70 participants | 138 participants | 68 participants |
| Sex: Female, Male Female | 70 Participants | 138 Participants | 68 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 70 | 0 / 68 |
| other Total, other adverse events | 57 / 70 | 56 / 68 |
| serious Total, serious adverse events | 0 / 70 | 2 / 68 |
Outcome results
Primary
Comparison of Cumulative Incidence of Anti-pegfilgrastim Antibodies (Binding and Neutralizing) to Pegfilgrastim Between Treatment Groups at the End of Cycle 4 (Day 84).
The difference in cumulative incidence of anti-pegfilgrastim antibodies (binding and neutralizing) (measured as difference in proportion of patients with antibodies) to Pegfilgrastim between study groups at the end of cycle 4 will be calculated. Those samples confirmed to be positive for binding antibodies were analyzed for presence of neutralizing antibodies to Pegfilgrastim.
Time frame: End of cycle 4, Day 84
Population: Intention-to-treat analysis population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lupin's Pegfilgrastim | Comparison of Cumulative Incidence of Anti-pegfilgrastim Antibodies (Binding and Neutralizing) to Pegfilgrastim Between Treatment Groups at the End of Cycle 4 (Day 84). | 0.0145 Proportion of patients with antibodies |
| Neulasta® | Comparison of Cumulative Incidence of Anti-pegfilgrastim Antibodies (Binding and Neutralizing) to Pegfilgrastim Between Treatment Groups at the End of Cycle 4 (Day 84). | 0.0441 Proportion of patients with antibodies |
Comparison: Analysis population : ITTp-value: 0.007Difference in proportion
Secondary
Comparison of Cumulative Incidence of Anti-peg Antibodies (Binding and Neutralizing) Between Treatment Groups at the End of Cycle 4 (Day 84).
The presence of anti-peg antibodies (binding) (measured as difference in proportion of patients with antibodies) between treatment groups at the end of cycle 4 (Day 84) were compared and analysis for the ITT population
Time frame: Day 84.
Population: Intention to treat population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lupin's Pegfilgrastim | Comparison of Cumulative Incidence of Anti-peg Antibodies (Binding and Neutralizing) Between Treatment Groups at the End of Cycle 4 (Day 84). | 0.0145 Proportion of patients with antibodies |
| Neulasta® | Comparison of Cumulative Incidence of Anti-peg Antibodies (Binding and Neutralizing) Between Treatment Groups at the End of Cycle 4 (Day 84). | 0 Proportion of patients with antibodies |
Comparison: Analysis population: ITTp-value: <0.001Difference in proportion
Secondary
Comparison of Incidence of Anti-pegfilgrastim Antibodies (Binding & Neutralizing) to Pegfilgrastim Between Treatment Groups on Day 10, Day 21, Day 42, Day 63 and Day 84
Comparison of incidence of anti-pegfilgrastim antibodies (binding & neutralizing) (measured as difference in proportion of patients with antibodies) to pegfilgrastim between treatment groups on Day 10, Day 21, Day 42, Day 63, Day 84. Analysis population : ITT
Time frame: Assessment at each study visit on Day 10, Day 21, Day 42, Day 63, Day 84
Population: The Intention-to-Treat (ITT) population included all patients who received at least one dose of study medication and subsequently provided immunogenicity variable data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lupin's Pegfilgrastim | Comparison of Incidence of Anti-pegfilgrastim Antibodies (Binding & Neutralizing) to Pegfilgrastim Between Treatment Groups on Day 10, Day 21, Day 42, Day 63 and Day 84 | Day 21 | 0 Participants |
| Lupin's Pegfilgrastim | Comparison of Incidence of Anti-pegfilgrastim Antibodies (Binding & Neutralizing) to Pegfilgrastim Between Treatment Groups on Day 10, Day 21, Day 42, Day 63 and Day 84 | Day 63 | 0 Participants |
| Lupin's Pegfilgrastim | Comparison of Incidence of Anti-pegfilgrastim Antibodies (Binding & Neutralizing) to Pegfilgrastim Between Treatment Groups on Day 10, Day 21, Day 42, Day 63 and Day 84 | Day 42 | 1 Participants |
| Lupin's Pegfilgrastim | Comparison of Incidence of Anti-pegfilgrastim Antibodies (Binding & Neutralizing) to Pegfilgrastim Between Treatment Groups on Day 10, Day 21, Day 42, Day 63 and Day 84 | Day 84 (EOS) | 0 Participants |
| Lupin's Pegfilgrastim | Comparison of Incidence of Anti-pegfilgrastim Antibodies (Binding & Neutralizing) to Pegfilgrastim Between Treatment Groups on Day 10, Day 21, Day 42, Day 63 and Day 84 | Day 10 | 1 Participants |
| Neulasta® | Comparison of Incidence of Anti-pegfilgrastim Antibodies (Binding & Neutralizing) to Pegfilgrastim Between Treatment Groups on Day 10, Day 21, Day 42, Day 63 and Day 84 | Day 84 (EOS) | 0 Participants |
| Neulasta® | Comparison of Incidence of Anti-pegfilgrastim Antibodies (Binding & Neutralizing) to Pegfilgrastim Between Treatment Groups on Day 10, Day 21, Day 42, Day 63 and Day 84 | Day 10 | 0 Participants |
| Neulasta® | Comparison of Incidence of Anti-pegfilgrastim Antibodies (Binding & Neutralizing) to Pegfilgrastim Between Treatment Groups on Day 10, Day 21, Day 42, Day 63 and Day 84 | Day 21 | 1 Participants |
| Neulasta® | Comparison of Incidence of Anti-pegfilgrastim Antibodies (Binding & Neutralizing) to Pegfilgrastim Between Treatment Groups on Day 10, Day 21, Day 42, Day 63 and Day 84 | Day 42 | 1 Participants |
| Neulasta® | Comparison of Incidence of Anti-pegfilgrastim Antibodies (Binding & Neutralizing) to Pegfilgrastim Between Treatment Groups on Day 10, Day 21, Day 42, Day 63 and Day 84 | Day 63 | 1 Participants |
Secondary
Secondary Immunogenicity Endpoint
Comparison of incidence of anti-peg antibodies (binding & neutralizing) (measured as difference in proportion of patients with antibodies) between treatment groups on Day 10, Day 21, Day 42, Day 63 and Day 84. Analysis population: ITT population
Time frame: Day 10, Day 21, Day 42, Day 63 and Day 84.
Population: The Intention-to-Treat (ITT) population included all patients who received at least one dose of study medication and subsequently provided immunogenicity variable data.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Lupin's Pegfilgrastim | Secondary Immunogenicity Endpoint | Day 21 | 0 Participants |
| Lupin's Pegfilgrastim | Secondary Immunogenicity Endpoint | Day 63 | 0 Participants |
| Lupin's Pegfilgrastim | Secondary Immunogenicity Endpoint | Day 42 | 1 Participants |
| Lupin's Pegfilgrastim | Secondary Immunogenicity Endpoint | Day 84 (EOS) | 0 Participants |
| Lupin's Pegfilgrastim | Secondary Immunogenicity Endpoint | Day 10 | 0 Participants |
| Neulasta® | Secondary Immunogenicity Endpoint | Day 84 (EOS) | 0 Participants |
| Neulasta® | Secondary Immunogenicity Endpoint | Day 10 | 0 Participants |
| Neulasta® | Secondary Immunogenicity Endpoint | Day 21 | 0 Participants |
| Neulasta® | Secondary Immunogenicity Endpoint | Day 42 | 0 Participants |
| Neulasta® | Secondary Immunogenicity Endpoint | Day 63 | 0 Participants |