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.

NCT02650193 | Completed Phase 2 Results

• 3 other identifiers: ZIN-130-1504C12210022015-002057-35
• Study Type: interventional
• Target: 25
• Locations: 2 countries
• Sites: 7

Brief 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.

Conditions

Non-metastatic Breast Cancer

Keywords

HSP-130 Phase 1-2 Study in patients with Breast cancer

Outcome Measures

Primary Outcomes (6)

• Area Under the Effect Curve for Absolute Neutrophil Count (AUECANC): Cycle 0

  Absolute neutrophil count (ANC) is a measure of the number of neutrophil granulocytes (also known as polymorphonuclear cells, PMN's, polys, granulocytes, segmented neutrophils or segs) present in the blood.

  Cycle 0: 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 0

  AUCinf = Area under the serum concentration of HSP-130 versus time curve (AUC) from the time of dose administration to extrapolated infinite time (0-inf).

  Cycle 0: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose

• Maximum Observed Serum Concentration (Cmax): Cycle 0

  Cycle 0: Predose (0 hour), 6, 12, 24, 48, 96, 144, 192, 240 and 312 hours post-dose

• Duration of Severe Neutropenia (DSN): Cycle 1

  Severe Neutropenia was defined as grade 4 neutropenia in which the ANC was \< 0.5 x10\^9 per liter. DSN was defined as the days with grade 4 neutropenia (ANC \< 0.5 x10\^9/L).

  Cycle 1: 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 of Last Measurable Concentration (AUCt): Cycle 1 and Cycle 4

  AUC0-t= Area under the serum concentration of HSP-130 versus time curve from the time of dose administration to time of last quantifiable concentration (0-t).

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

• Maximum Observed Serum Concentration (Cmax): Cycle 1 and Cycle 4

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

Secondary Outcomes (31)

• Maximum Effect for Absolute Neutrophil Count (ANC_Emax): Cycle 0

  Cycle 0: Predose (0 hour), 48, 96, 144, 192, 240 and 312 hours post-dose

• Time of Maximum Effect for Absolute Neutrophil Count (ANC_Tmax): Cycle 0

  Cycle 0: Predose (0 hour), 48, 96, 144, 192, 240 and 312 hours post-dose

• Area Under the Effect Curve for CD34+ (AUECCD34+): Cycle 0

  Cycle 0: Predose (0 hour), 48, 96, 144, 192, 240 and 312 hours post-dose

• Maximum Effect for CD34+ Count (CD34+_Emax): Cycle 0

  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

  Cycle 0: Predose (0 hour), 48, 96, 144, 192, 240 and 312 hours post-dose

Other Outcomes (9)

• Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Baseline up to approximately Day 94

• Number of Participants With Treatment-Emergent Adverse Events (AEs) of Special Interest

  Baseline up to approximately Day 94

• Number of Participants With Laboratory Abnormalities

  Baseline up to approximately Day 94

Study Arms (1)

HSP-130

EXPERIMENTAL

Cycle 0: Regimen A: HSP 130, 3 mg, single SC injection in the deltoid region (n = 6) Regimen B: HSP 130, 6 mg, single SC injection in the deltoid region (n = 6) Cycles 1-4: Regimen B (n = 12): HSP 130, 6 mg, single SC injection in the deltoid region, at least 24 hours after administration of chemotherapy in Cycle 1, Cycle 2, Cycle 3, and Cycle 4. Potential Regimen A (n = 12): 3 mg with background chemotherapy: Inclusion of this cohort will be based on assessment of comparability between Regimens A and B in Cycle 0 for ANC and CD34+ as defined above. If performed, this regimen will be HSP 130, 3 mg, single SC injection in the deltoid region, at least 24 hours after administration of chemotherapy in Cycle 1, Cycle 2, Cycle 3, and Cycle 4, as appropriate. Conditional Regimen C (12 mg):This cohort will not be initiated until data from cycle 0 for 3 mg and 6 mg and Cycles 1-4 for 6 mg has been reviewed and analyzed.

Drug: HSP-130

Interventions

HSP-130 DRUG

Dosage will vary per each cohort: (Five independent cohorts) Cycle 0 Regimen A - 3 mg Cycle 0 Regimen B - 6 mg Cycles 1-4 Regimen B - 6 mg Cycles 1-4 Regimen A (Potential)- 3 mg Cycles 1-4 Regimen C (Conditional)- 12 mg

Also known as: Pegylated filgrastim

HSP-130

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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 systemically active antibiotics within 72 hours before chemotherapy
• Known infection with HIV
• Known sickle cell disease
• Known severe persistent drug-induced myelosuppression

Sponsors & Collaborators

• Pfizer: lead
• Hospira, now a wholly owned subsidiary of Pfizer: collaborator

Study Sites (7)

CRU Hungary Kft.,CRU Early Phase Unit, Miskolci Semmelweis Kórház és Egyetemi Oktató Kórház

Miskolc, BAZ Megye, 3529, Hungary

Location

Debreceni Egyetem Klinikai Központ, ÁOK, Onkológiai Klinika

Debrecen, Hajdú-bihar Megye, 4032, Hungary

Location

Országos Onkológiai Intézet

Budapest, 1122, Hungary

Location

Hospital Universitario Arnau de Vilanova

Lleida, Catalonia, 25198, Spain

Location

Hospital Universitario de Fuenlabrada, Servicio de oncologia

Fuenlanbrada, Madrid, 28942, Spain

Location

START Madrid - CIOCC, Unidad de fases 1 planta 3, Hospital Universitario HM Sanchinarro

Madrid, 28050, Spain

Location

Hospital Arnau de Vilanova. planta 6, unidad de Oncología

Valencia, 46015, Spain

Location

Related Publications (1)

• Yao HM, Jones SR, Morales S, Moosavi S, Zhang J, Freyman A, Ottery FD. Phase I/II study to assess the clinical pharmacology and safety of single ascending and multiple subcutaneous doses of PF-06881894 in women with non-distantly metastatic breast cancer. Cancer Chemother Pharmacol. 2021 Dec;88(6):1033-1048. doi: 10.1007/s00280-021-04355-6. Epub 2021 Oct 7.

  PMID: 34618197 DERIVED

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2016
• First Posted: January 8, 2016
• Study Start: December 1, 2015
• Primary Completion: October 1, 2017
• Study Completion: October 1, 2017
• Last Updated: October 23, 2018
• Results First Posted: October 23, 2018

Record last verified: 2018-09

Locations

ES (4); HU (3)