Phase 2
Completed N=25
A Study Of The Safety And Effects Of One Or More Doses Of HSP-130 Injected Under The Skin In Women With Breast Cancer That Has Not Spread To Distant Sites In The Body.
Non-metastatic Breast Cancer
Source: ClinicalTrials.gov NCT02650193 ↗
Enrolled (actual)
25
Serious AEs
8.0%
Results posted
Oct 2018
Primary outcomePrimary: Area Under the Effect Curve for Absolute Neutrophil Count (AUECANC): Cycle 0 — 3900.482; 5880.985 hour*10^9 Neutrophils per Liter
Summary
This is a study of how one or more injections of HSP-130 under the skin effect the white blood cell counts and drug levels in women with breast cancer that has not spread to distant sites in the body (non-metastatic). This will be studied in women before breast surgery or while receiving chemotherapy. Safety will also be studied.
Additionally, the purpose of this study is to evaluate the effects and safety of single and multiple doses of HSP-130 in subjects with non-metastatic breast cancer. This study will determine the dose to move forward for future clinical trials.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Area Under the Effect Curve for Absolute Neutrophil Count (AUECANC): Cycle 0 |
3900.482; 5880.985 | — |
| PRIMARY Area Under the Serum Concentration Time Curve From Time of Dose Administration to Time Infinity (AUCinf): Cycle 0 |
1425862.2; 5689476.1 | — |
| PRIMARY Maximum Observed Serum Concentration (Cmax): Cycle 0 |
38026.7; 155766.7 | — |
| PRIMARY Duration of Severe Neutropenia (DSN): Cycle 1 |
0.667 | — |
| PRIMARY Area Under the Serum Concentration Time Curve From Time of Dose Administration to Time of Last Measurable Concentration (AUCt): Cycle 1 and Cycle 4 |
10084193.7; 6017621.6 | — |
| PRIMARY Maximum Observed Serum Concentration (Cmax): Cycle 1 and Cycle 4 |
118130.8; 95200.0 | — |
| SECONDARY Maximum Effect for Absolute Neutrophil Count (ANC_Emax): Cycle 0 |
24.512; 43.257 | — |
| SECONDARY Time of Maximum Effect for Absolute Neutrophil Count (ANC_Tmax): Cycle 0 |
71.950; 47.800 | — |
| SECONDARY Area Under the Effect Curve for CD34+ (AUECCD34+): Cycle 0 |
1749.523; 2752.198 | — |
| SECONDARY Maximum Effect for CD34+ Count (CD34+_Emax): Cycle 0 |
13.970; 27.343 | — |
| SECONDARY Time of Maximum Effect for CD34+ Count (CD34+ Tmax): Cycle 0 |
96.000; 96.600 | — |
| SECONDARY Area Under the Effect Curve for Absolute Neutrophil Count From Time of Dose Administration to Time Infinity (AUEC_ANC Inf): Cycle 0 |
5254.288; 6576.165 | — |
| SECONDARY Area Under the Effect Curve From Time of Dose Administration to Time Infinity for CD34 + (AUEC_CD34+ Inf): Cycle 0 |
1835.221; 3159.470 | — |
| SECONDARY Area Under the Serum Concentration Time Curve From the Time of Dose Administration to the Time of Last Measurable Concentration (AUCt): Cycle 0 |
1410202.6; 5677700.3 | — |
| SECONDARY Time To Achieve Maximum Serum Concentration (Tmax): Cycle 0 |
12.0; 23.5 | — |
| SECONDARY Elimination Half-Life (t1/2): Cycle 0 |
50.0; 48.8 | — |
| SECONDARY Elimination Rate Constant (λz): Cycle 0 |
0.015; 0.015 | — |
| SECONDARY Apparent Clearance (CL/F): Cycle 0 |
4235.6; 1655.9 | — |
| SECONDARY Protein-Content Corrected Area Under the Serum Concentration Time Curve From Time of Dose Administration to Time Infinity (AUCinf): Cycle 0 |
1440264.8; 5689476.1 | — |
| SECONDARY Protein-Content Corrected Area Under the Serum Concentration Time Curve From Time of Dose Administration to Time of Last Measurable Concentration (AUCt): Cycle 0 |
1424447.1; 5677700.3 | — |
| SECONDARY Protein-Content Corrected Maximum Observed Serum Concentration (Cmax): Cycle 0 |
38410.8; 155766.7 | — |
| SECONDARY Duration of Severe Neutropenia (DSN): Cycle 4 |
0.667 | — |
| SECONDARY Absolute Neutrophil Count Nadir Concentration: Cycle 1 and Cycle 4 |
1.132; 1.623 | — |
| SECONDARY Time of ANC Nadir Concentration: Cycle 1 and Cycle 4 |
129.231; 142.154 | — |
| SECONDARY Area Under the Effect Curve (AUEC_ANCt): Cycle 1 and Cycle 4 |
2540.285; 3186.542 | — |
| SECONDARY Area Under the Effect Curve for Absolute Neutrophil Count From Time of Dose Administration to Time Infinity (AUEC_ANC Inf): Cycle 1 and Cycle 4 |
5636.963; 12399.370 | — |
| SECONDARY Incidence of Febrile Neutropenia: Cycle 1 and Cycle 4 |
1; 0 | — |
| SECONDARY Incidence of Severe Neutropenia: Cycle 1 and Cycle 4 |
5; 5 | — |
| SECONDARY Time to ANC Recovery: Cycle 1 and Cycle 4 |
2.615; 2.000 | — |
| SECONDARY Area Under the Serum Concentration Time Curve From Time of Dose Administration to Time Infinity (AUCinf): Cycle 1 and Cycle 4 |
10093213.5; 6425013.3 | — |
| SECONDARY Time To Achieve Maximum Serum Concentration (Tmax): Cycle 1 and Cycle 4 |
24.1; 23.5 | — |
| SECONDARY Elimination Half-Life (t1/2): Cycle 1 and Cycle 4 |
30.7; 29.5 | — |
| SECONDARY Elimination Rate Constant (λz): Cycle 1 and Cycle 4 |
0.026; 0.025 | — |
| SECONDARY Apparent Clearance (CL/F): Cycle 1 and Cycle 4 |
1326.8; 2342.8 | — |
| SECONDARY Protein-Content Corrected Area Under the Serum Concentration Time Curve From Time of Dose Administration to Time of Last Measurable Concentration (AUCt): Cycle 1 and Cycle 4 |
10087666.8; 6045733.4 | — |
| SECONDARY Protein-Content Corrected Area Under the Serum Concentration Time Curve From Time of Dose Administration to Time Infinity (AUCinf): Cycle 1 and Cycle 4 |
10096698.3; 6454443.8 | — |
| SECONDARY Protein-Content Corrected Maximum Observed Serum Concentration (Cmax): Cycle 1 and Cycle 4 |
118173.0; 95670.1 | — |
Eligibility Criteria
Inclusion Criteria
- A subject will be eligible for study participation if all of the following criteria are met at Screening:
- Is informed, has been given ample time and opportunity to read about participation in the study and has signed and dated the written informed consent form approved by an Independent Ethics committee (IEC) prior to any study related activities
- Females ≥ 18 years
- Histologically confirmed and documented invasive breast cancer
- Breast cancer without evidence of distant metastases (Stage 4) based on staging work-up
- Chemotherapy naive, who have not received chemotherapy in the neoadjuvant setting and who are candidates for chemotherapy in the adjuvant setting of taxane/cyclophosphamide-based regimen, e.g., TAC, as background chemotherapy
- Zubrod/WHO/ECOG performance status ≤ 2
- Adequate bone marrow, hepatic, and renal function reserve as evidenced by:
- Hemoglobin ≥ 10 mg/dl
- ANC ≥ 1.5 x 10^9/L
- Platelet count of ≥ 100 x 10^9/L
- Total bilirubin ≤ 2 mg/dl
- Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤ 3 x the upper limit of normal (ULN) of the reference lab
- Serum creatinine of ≤ 1.5 x ULN for reference lab or estimated glomerular filtration rate (eGFR) of ≥ 60 mg/min
- Body mass index (BMI) of 19 to 40 kg/m^2 , inclusive
- Subjects of childbearing potential, and their partners, agree to pregnancy prevention throughout the duration of the study (through the Follow-up Visit). Specific type of pregnancy prevention should be discussed with, and acceptable to, the treating oncologist in the context of the tumoral hormone receptor status. Subjects and their partners must agree to use of an effective method of contraception, to avoid impregnation of females throughout the course of the study
Medically acceptable forms of birth control can include, with approval of the treating physician:
- Barrier methods (condom or diaphragm with spermicide)
- Intrauterine device (IUD)
- Hormone contraceptives (such as oral [pill], injection, skin patch, implant, cervical ring)
- Subjects using oral contraceptives must be on a stable regimen for at least 3 months prior to Screening. Sexually active subjects must use contraception while on HSP-130 from admission to the final Follow-up Visit
- Able to understand verbal or written instructions and comply with all study requirements, to communicate effectively with study personnel and is available for the planned duration of the study
Exclusion Criteria
- A subject will NOT be eligible for study participation if any of the following criteria are met at Screening:
- Previous G-CSF exposure, including filgrastim, lenograstim, pegfilgrastim, lipegfilgrastim, granulocyte/macrophage colony stimulating growth factor (GM-CSF), or any other branded or biosimilar G-CSF
- Prior autologous stem cell harvest of any type
- Drug sensitivity, allergic reaction, or known hypersensitivity or idiosyncratic reaction to E. coli - derived proteins, filgrastim, other G-CSFs, or pegylated agents
- Known hypersensitivity to docetaxel, polysorbate 80, or doxorubicin
- For subjects receiving doxorubicin, no concurrent use of inhibitors and inducers of CYP3A4, CYP2D6, and/or P-gp or with trastuzumab due to increased risk of cardiac dysfunction
- Chemotherapy other than that included in this study (taxane/cyclophosphamide-based regimen, e.g., TAC or TC) or neoadjuvant chemotherapy; or known immunosuppressive agents including chronic oral corticosteroid use, or radiation therapy within 4 weeks of first dose of HSP-130, prior bone marrow or stem cell transplantation, or malignancy within 5 years
- Known HER2 + ( overexpressing breast cancer)
- Known triple negative (estrogen receptor-negative, progesterone receptor-negative and HER2-negative) breast cancer
- ≥ Grade 2 underlying neuropathy
- Current diagnosis of active tuberculosis or other severe infection, such as sepsis, abscesses or opportunistic infections
- Treatment with syst
Data sourced from ClinicalTrials.gov (NCT02650193). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.