Clinical trial NCT02725606: Study to Assess the Safety, Tolerability, and Pharmacokinetics/Pharmacodynamics of GW003 in Patients With Breast Cancer
Official title: A Phase I Study to Evaluate the Safety, Tolerability, and Pharmacokinetics/Pharmacodynamics of Human Serum Albumin/Human Granulocyte-Colony Stimulating Factor(I) Fusion Protein for Injection (GW003) in Patients With Breast Cancer
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Chemotherapy-induced Neutropenia
Keywords: Neutropenia
Breast Cancer
GW003
Lead sponsor: Jiangsu T-Mab Biopharma Co.,Ltd
Sponsor class: INDUSTRY
First posted: 2016-04-01
Enrollment: 30
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of the present trial is to evaluate the safety, tolerability and pharmacokinetics(PK)/pharmacodynamics(PD) of single subcutaneous injection of GW003 in breast cancer patients. Moreover, the efficacy will be assessed preliminary.

Detailed description: This is an single-center, open-label, randomized, active-controlled phase I study evaluating tolerability and pharmacokinetics/pharmacodynamics of single subcutaneous injections of GW003 in the breast cancer patients.GW003 is recombinant human serum albumin/human granulocyte-colony stimulating factor(I)fusion protein .It is a long-acting G-CSF(Granulocyte-Colony Stimulating Factor). In this study, participants will be administered a single dose of GW003. Every subject will only accept one dose. In addition to tolerability and safety, pharmacokinetics/pharmacodynamics, preliminary efficacy and immunogenicity of GW003 will be evaluated as well.

Eligibility criteria: Inclusion Criteria:

* Aged 18 years to 70 years, female
* Patients with histologically-confirmed breast cancer and plan to accept adjuvant chemotherapy(epirubicin plus cyclophosphamide)
* Have an Eastern Cooperative Oncology Group(ECOG) performance status≤2
* Have no clinically significant impairment in cardiac, liver and kidney
* Adequate hematologic, hepatic and renal function which should meet the following requirements:

  1. Absolute neutrophil count(ANC)≥1.5 x 10\^9/L
  2. Blood platelet(PLT)≥100 x 10\^9/L
  3. Serum creatinine(sCr)≤1.5 times the upper limit of normal(ULN)
  4. Total bilirubin(TBIL)≤1.5×ULN
  5. Aspartate aminotransferase(AST) /serum glutamic-oxaloacetic transaminase(SGOT) and/or alanine aminotransferase(ALT)/serum glutamic pyruvic transaminase(SGPT) ≤ 2.5 x ULN
  6. Hemoglobin(Hb)\>9 g/dL
  7. Alkaline phosphatase(ALP)≤1.5×ULN
* Expected to comply with protocol
* With urine human chorionic gonadotropin (hCG) negative
* Signed informed consent

Exclusion Criteria:

* With acute infection
* With history of bone marrow transplant and/or stem cell transplant
* With primary hematological diseases, such as myelodysplastic syndromes, aplastic anemia, sickle cell anemia
* Received surgery within 3 weeks before chemotherapy
* Received G-CSF within 4 weeks before involved in this study
* Females who are pregnant or lactating
* Participated in other clinical trials at the same time or within 4 weeks before screening
* Known allergy to chemotherapy drugs,recombinant human granulocyte-colony stimulating factor rh(rhG-CSF) or any other biological products
* With cacoethic addiction such as drug abuse or alcoholism
* With other cases which is not suitable for this study judged by investigator

Primary outcomes:
measure: Frequency of adverse events (AEs) and serious adverse events (SAEs) which are related to GW003 as assessed by CTCAE v4.03
timeFrame: 21days
Secondary outcomes:
measure: Maximum observed maximum plasma concentration [Cmax]
timeFrame: 21days
measure: Time to reach the maximum observed plasma concentration [Tmax]
timeFrame: 21days
measure: Area under the plasma concentration-time curve from time zero to infinity[AUC0-inf]
timeFrame: 21days
measure: Area under the plasma concentration-time curve from time zero to time 't' where t is a defined time point after administration [AUC0-t]
timeFrame: 21days
measure: Terminal elimination half-life[T1/2]
timeFrame: 21days
measure: Absolute neutrophil count[ANC]
timeFrame: 21days
measure: CD34+ count
timeFrame: 21days
measure: Time to absolute neutrophil count(ANC) recovery
timeFrame: 21days
measure: Incidence of severe neutropenia
timeFrame: 21days
measure: Duration of severe neutropenia(DSN)
timeFrame: 21days
measure: ANC nadir
timeFrame: 21days
measure: Frequency of subjects with anti-GW003 antibody
timeFrame: 21days
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Fudan University Shanghai Cancer Center
state: Shanghai
Study officials:
affiliation: Principal Investigator
name: Xichun Hu
role: PRINCIPAL_INVESTIGATOR
References: