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.

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02650193
• Date of registration: 04/01/2016
• Prospective Registration: No
• Primary sponsor: Pfizer
• Public title: 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.
• Scientific title: A Phase 1-2 Ascending Dose Study To Assess The Pharmacodynamics, Pharmacokinetics, And Safety Of Hsp-130 In Subjects With Non-metastatic Breast Cancer Following Single-dose And Multiple-dose Administration By Subcutaneous Injection
• Date of first enrolment: December 2015
• Target sample size: 25
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02650193
• Study type: Interventional
• Study design: Intervention model: Parallel Assignment. Primary purpose: Other. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Hungary, Spain

Contacts

• Name: Pfizer CT.gov Call Center
• Affiliation: Pfizer

Key inclusion & exclusion criteria

Inclusion Criteria:

- A subject will be eligible for study participation if all of the following criteria
are met at Screening:

1. 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

2. Females = 18 years

3. Histologically confirmed and documented invasive breast cancer

4. Breast cancer without evidence of distant metastases (Stage 4) based on staging
work-up

5. 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

6. Zubrod/WHO/ECOG performance status = 2

7. Adequate bone marrow, hepatic, and renal function reserve as evidenced by:

1. Hemoglobin = 10 mg/dl

2. ANC = 1.5 x 10^9/L

3. Platelet count of = 100 x 10^9/L

4. Total bilirubin = 2 mg/dl

5. Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) = 3 x
the upper limit of normal (ULN) of the reference lab

6. Serum creatinine of = 1.5 x ULN for reference lab or estimated glomerular
filtration rate (eGFR) of = 60 mg/min

8. Body mass index (BMI) of 19 to 40 kg/m^2 , inclusive

9. 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:

1. Barrier methods (condom or diaphragm with spermicide)

2. Intrauterine device (IUD)

3. Hormone contraceptives (such as oral [pill], injection, skin patch, implant,
cervical ring)

4. 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

10. 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:

1. 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

2. Prior autologous stem cell harvest of any type

3. Drug sensitivity, allergic reaction, or known hypersensitivity or idiosyncratic
reaction to E. coli - derived proteins, filgrastim, other G-CSFs, or pegylated
agents

4. Known hypersensitivity to docetaxel, polysorbate 80, or doxorubicin

5. 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

6. 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

7. Known HER2 + ( overexpressing breast cancer)

8. Known triple negative (estrogen receptor-negative, progesterone receptor-negative
and HER2-negative) breast cancer

9. = Grade 2 underlying neuropathy

10. Current diagnosis of active tuberculosis or other severe infection, such as
sepsis, abscesses or opportunistic infections

11. Treatment with systemically active antibiotics within 72 hours before
chemotherapy

12. Known infection with HIV

13. Known sickle cell disease

14. Known severe persistent drug-induced myelosuppression

15. New York Heart Association (NYHA) class III or IV heart failure, severe
uncontrolled cardiac disease (unstable angina, clinically significant ECG
abnormalities) or MI within the previous 6 months before the first administration
of HSP-130

16. Any malignancy other than breast cancer, with exception of adequately treated
squamous or basal cell carcinoma of the skin or cervical carcinoma in situ,
within 5 years before the first administration of the HSP-130

17. Current or recent treatment (within 30 days before the first administration of
the HSP-130) with any other investigational medicinal product

18. Pregnancy or lactation; Subjects planning to be pregnant or to breastfeed before,
during, or within 12 months after administration of the HSP-130 are not permitted
to enroll in the study

19. Received a live, live-attenuated, or non-live vaccine within 4 weeks before the
first administration of the HSP-130

20. Patient has evidence of any other coexisting disease or medical or psychological
condition, metabolic dysfunction, physical examination finding or clinical lab
finding giving reasonable suspicion of a disease or condition that
contraindicated the use of an HSP-130, or patient is high risk for treatment
complication



Age minimum: 18 Years
Age maximum: N/A
Gender: Female

Health Condition(s) or Problem(s) studied

Non-metastatic Breast Cancer

Intervention(s)

Drug: HSP-130

Primary Outcome(s)

Area Under the Serum Concentration Time Curve From Time of Dose Administration to Time Infinity (AUCinf): Cycle 0 [Time Frame: Cycle 0: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose]

Area Under the Serum Concentration Time Curve From Time of Dose Administration to Time of Last Measurable Concentration (AUCt): Cycle 1 and Cycle 4 [Time Frame: Cycle 1 and 4: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose]

Area Under the Effect Curve for Absolute Neutrophil Count (AUECANC): Cycle 0 [Time Frame: Cycle 0: Predose (0 hour), 48, 96, 144, 192, 240 and 312 hours post-dose]

Maximum Observed Serum Concentration (Cmax): Cycle 1 and Cycle 4 [Time Frame: Cycle 1 and 4: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose]

Duration of Severe Neutropenia (DSN): Cycle 1 [Time Frame: Cycle 1: Predose (0 hour), 48, 96, 144, 192, 240 and 312 hours post-dose]

Maximum Observed Serum Concentration (Cmax): Cycle 0 [Time Frame: Cycle 0: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose]

Secondary Outcome(s)

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 [Time Frame: Cycle 1 and 4: Predose (0 hour), 48, 96, 144, 192, 240 and 312 hours post-dose]

Area Under the Serum Concentration Time Curve From Time of Dose Administration to Time Infinity (AUCinf): Cycle 1 and Cycle 4 [Time Frame: Cycle 1 and 4: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose]

Protein-Content Corrected Maximum Observed Serum Concentration (Cmax): Cycle 1 and Cycle 4 [Time Frame: Cycle 1 and 4: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose]

Apparent Clearance (CL/F): Cycle 1 and Cycle 4 [Time Frame: Cycle 1 and 4: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose]

Area Under the Effect Curve for Absolute Neutrophil Count From Time of Dose Administration to Time Infinity (AUEC_ANC Inf): Cycle 0 [Time Frame: Cycle 0: Predose (0 hour), 48, 96, 144, 192, 240 and 312 hours post-dose]

Area Under the Effect Curve (AUEC_ANCt): Cycle 1 and Cycle 4 [Time Frame: Cycle 1 and 4: Predose (0 hour), 48, 96, 144, 192, 240, and 312 hours post-dose]

Incidence of Severe Neutropenia: Cycle 1 and Cycle 4 [Time Frame: Cycle 1 and 4: Predose (0 hour), 48, 96, 144, 192, 240, and 312 hours post-dose]

Maximum Effect for Absolute Neutrophil Count (ANC_Emax): Cycle 0 [Time Frame: Cycle 0: Predose (0 hour), 48, 96, 144, 192, 240 and 312 hours post-dose]

Protein-Content Corrected Area Under the Serum Concentration Time Curve From Time of Dose Administration to Time Infinity (AUCinf): Cycle 1 and Cycle 4 [Time Frame: Cycle 1 and 4: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose]

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 [Time Frame: Cycle 1 and 4: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose]

Protein-Content Corrected Maximum Observed Serum Concentration (Cmax): Cycle 0 [Time Frame: Cycle 0: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose]

Time To Achieve Maximum Serum Concentration (Tmax): Cycle 0 [Time Frame: Cycle 0: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose]

Absolute Neutrophil Count Nadir Concentration: Cycle 1 and Cycle 4 [Time Frame: Cycle 1 and 4: Predose (0 hour), 48, 96, 144, 192, 240, and 312 hours post-dose]

Elimination Rate Constant (?z): Cycle 0 [Time Frame: Cycle 0: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose]

Protein-Content Corrected Area Under the Serum Concentration Time Curve From Time of Dose Administration to Time Infinity (AUCinf): Cycle 0 [Time Frame: Cycle 0: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose]

Area Under the Serum Concentration Time Curve From the Time of Dose Administration to the Time of Last Measurable Concentration (AUCt): Cycle 0 [Time Frame: Cycle 0: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose]

Incidence of Febrile Neutropenia: Cycle 1 and Cycle 4 [Time Frame: Cycle 1 and 4: Predose (0 hour), 48, 96, 144, 192, 240 and 312 hours post-dose]

Maximum Effect for CD34+ Count (CD34+_Emax): Cycle 0 [Time Frame: Cycle 0: Predose (0 hour), 48, 96, 144, 192, 240 and 312 hours post-dose]

Time of ANC Nadir Concentration: Cycle 1 and Cycle 4 [Time Frame: Cycle 1 and 4: Predose (0 hour), 48, 96, 144, 192, 240, and 312 hours post-dose]

Time To Achieve Maximum Serum Concentration (Tmax): Cycle 1 and Cycle 4 [Time Frame: Cycle 1 and 4: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose]

Area Under the Effect Curve for CD34+ (AUECCD34+): Cycle 0 [Time Frame: Cycle 0: Predose (0 hour), 48, 96, 144, 192, 240 and 312 hours post-dose]

Apparent Clearance (CL/F): Cycle 0 [Time Frame: Cycle 0: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose]

Area Under the Effect Curve From Time of Dose Administration to Time Infinity for CD34 + (AUEC_CD34+ Inf): Cycle 0 [Time Frame: Cycle 0: Predose (0 hour), 48, 96, 144, 192, 240 and 312 hours post-dose]

Elimination Half-Life (t1/2): Cycle 1 and Cycle 4 [Time Frame: Cycle 1 and 4: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose]

Protein-Content Corrected Area Under the Serum Concentration Time Curve From Time of Dose Administration to Time of Last Measurable Concentration (AUCt): Cycle 0 [Time Frame: Cycle 0: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose]

Time to ANC Recovery: Cycle 1 and Cycle 4 [Time Frame: Cycle 1 and 4: Predose (0 hour), 48, 96, 144, 192, 240 and 312 hours post-dose]

Duration of Severe Neutropenia (DSN): Cycle 4 [Time Frame: Cycle 4: Predose (0 hour), 48, 96, 144, 192, 240 and 312 hours post-dose]

Elimination Half-Life (t1/2): Cycle 0 [Time Frame: Cycle 0: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose]

Elimination Rate Constant (?z): Cycle 1 and Cycle 4 [Time Frame: Cycle 1 and 4: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose]

Time of Maximum Effect for Absolute Neutrophil Count (ANC_Tmax): Cycle 0 [Time Frame: Cycle 0: Predose (0 hour), 48, 96, 144, 192, 240 and 312 hours post-dose]

Time of Maximum Effect for CD34+ Count (CD34+ Tmax): Cycle 0 [Time Frame: Cycle 0: Predose (0 hour), 48, 96, 144, 192, 240 and 312 hours post-dose]

Secondary ID(s)

ZIN-130-1504

2015-002057-35

C1221002

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Hospira, now a wholly owned subsidiary of Pfizer

Results

• Results available: Yes
• Date Posted: 23/10/2018
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02650193