E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Management of Neutropenia in Patients with Breast Cancer who are Candidates for Adjuvant and Neoadjuvant Chemotherapy with the Docetaxel + Cyclophosphamide (TC) Regimen |
|
E.1.1.1 | Medical condition in easily understood language |
Management of low neutrophil count in Patients with Breast Cancer |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10029354 |
E.1.2 | Term | Neutropenia |
E.1.2 | System Organ Class | 10005329 - Blood and lymphatic system disorders |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective and endpoint of this study is to assess the effect of test doses of HM10460A on the duration of severe neutropenia (DSN) during Cycle 1 in patients with breast cancer who are candidates for adjuvant or neoadjuvant chemotherapy. |
|
E.2.2 | Secondary objectives of the trial |
The secondary objectives and endpoints of this study are to determine the effect of test doses of HM10460A on the following:
Duration of severe neutropenia in Cycles 2-4
Absolute neutrophil count (ANC) in Cycles 1-4
Time to ANC recovery in Cycles 1-4
Depth of ANC nadir in Cycles 1-4
Febrile neutropenia (FN) rates by cycle and overall across Cycles 1-4
Safety profile
Number/duration of hospitalizations
Immunogenicity
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Given written informed consent (IC)
2. Has histologically confirmed breast cancer who is a candidate for adjuvant or neoadjuvant chemotherapy
3. Candidate for docetaxel and cyclophosphamide chemotherapy
4. Female or male ≥ 18 years of age
5. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
6. ANC ≥ 1.5 x 109/L
7. Platelet count ≥ 100 x 109/L
8. Creatinine ≤ 1.5 x upper limit of normal (ULN)
9. Total bilirubin ≤ 1.5 mg/dL ( 25.65 µmol/L)
10. Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) and/or alanine aminotransferase ALT/serum glutamic-pyruvic transaminase (SGPT) ≤ 2.5 x ULN
11. Hemoglobin > 9 g/dL
12. Alkaline phosphatase ≤ 1.5 x ULN
|
|
E.4 | Principal exclusion criteria |
1. Known sensitivity to Escherichia coli (E. coli) derived products (e.g., filgrastim, recombinant insulin [HUMULIN®], L-asparaginase, somatropin [HUMATROPE®] growth hormone, recombinant interferon alfa-2b [INTRON® A]) or known sensitivity to any of the products to be administered during dosing
2. Known human immunodeficiency virus (HIV) infection
3. Hepatitis B virus (HBV) or hepatitis C virus (HCV) diagnosis with detectable viral load or immunological evidence of chronic active disease
4. Active infection or any serious underlying medical condition, which would impair the ability of the patient to receive protocol treatment
5. Prior bone marrow or stem cell transplant
6. Major surgery (except for breast surgery related to the patient’s breast cancer diagnosis) within 4 weeks prior to enrollment
7. Presence of any other malignancy or history of prior malignancy within 5 years of study entry. Within 5 years, patients treated with curative intent for Stage I or II cancers are eligible provided they have a life expectancy of > 5 years. The 5-year exclusion rule does not apply to non-melanoma skin tumors and in situ cervical cancer
8. Currently enrolled in or 30 days have not passed since completing other investigational device or drug trial(s)
9. Prolonged exposure to glucocorticosteroids and immunosuppressive agents
10. Pregnant or breast-feeding (for patients of child-bearing potential)
11. Dementia or significantly altered mental status that would prohibit the understanding and giving of informed consent or limit study compliance.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
The primary objective and endpoint of this study is to assess the effect of test doses of HM10460A on the duration of severe neutropenia (DSN) during Cycle 1 in patients with breast cancer who are candidates for adjuvant or neoadjuvant chemotherapy. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Completion of Cycle 1 of chemotherapy treatment |
|
E.5.2 | Secondary end point(s) |
•Duration of Severe Neutropenia (DSN) in Cycles 2-4
•Absolute neutrophil count (ANC) in Cycles 1-4
•Time to ANC recovery in Cycles 1-4
•Depth of ANC nadir in Cycles 1-4
•Febrile neutropenia (FN) rates by cycle and overall across Cycles 1-4
•Safety profile
•Number/duration of hospitalizations
•Immunogenicity
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
•Duration of Severe Neutropenia (DSN) in Cycles 2-4: following the completion of Cycle 4 of chemotherapy
•Absolute neutrophil count (ANC) in Cycles 1-4: following the completion of Cycle 4 of chemotherapy
•Time to ANC recovery in Cycles 1-4: following the completion of Cycle 4 of chemotherapy
•Depth of ANC nadir in Cycles 1-4: following the completion of Cycle 4 of chemotherapy
•Febrile neutropenia (FN) rates by cycle and overall across Cycles 1-4: following the completion of Cycle 4 of chemotherapy
•Safety profile: following the completion of the safety follow up period (30 days after the End of Study Visit)
•Number/duration of hospitalizations: End of Study Visit
•Immunogenicity: End of Study Visit
|
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 16 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 26 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
Australia |
Czech Republic |
Hungary |
Israel |
Poland |
United States |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 7 |