PK and Drug Interaction Study of Utidelone Plus Capecitabine in Patients With Advanced Breast Cancer

Open, Multicenter, Phase Ic Clinical Study on the Pharmacokinetics and Drug Interactions of Utidelone Plus Capecitabine in Patients With Recurrent and Metastatic Breast Cancer

This trial is an open, multi-center, phase Ic clinical study on the pharmacokinetics and drug interactions of utidelone injection combined with capecitabine in patients with recurrent and metastatic breast cancer.

The purpose of this trial is:

1. To evaluate the pharmacokinetic characteristics of continuous intravenous administration of utidelone.
2. To evaluate the drug interaction of utidelone and capecitabine.

Study Overview

• Status: Completed
• Conditions: Advanced and Metastatic Breast Cancer
• Intervention / Treatment: Drug: Utidelone; Drug: Utidelone Injection; capecitabine

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China
      • Hunan Cancer Hospital
    • Changsha, Hunan, China
      • The Third Xiangya Hospital of Central South University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Voluntarily sign an informed consent form, have good compliance, and cooperate with relevant inspections.
2. Histologically and/or cytologically diagnosed patients with advanced, metastatic breast cancer.
3. Patients who have previously received at least one anthracycline and taxane drug therapy (neoadjuvant therapy, adjuvant therapy, or recurrence and metastasis therapy), or the investigator believes that they can be included in this study.
4. Age ≥18 years; physical condition score ECOG 0~2 points.
5. Within 4 weeks before enrollment, Neuropathy should be less than grade 2 (NCI CTCAE 5.0).

6. Within 1 week before enrollment, routine blood examinations were basically normal (based on the normal value of each research center laboratory):

   1. White blood cell count (WBC) ≥3.0×109/L;
   2. Neutrophil count (ANC) ≥ 1.5×109/L;
   3. Platelet count (PLT) ≥100×109/L.
   4. Hemoglobin ≥9g/dL.

7. Within 1 week before enrollment, liver and kidney function tests were basically normal (the normal value of each research center laboratory is standard):

   1. Total bilirubin (TBIL)≤1.5×upper limit of normal (ULN);
   2. Alanine aminotransferase (SGPT/ALT)≤2.5×ULN (for liver metastases≤5×ULN);
   3. Aspartate aminotransferase (SGOT/AST)≤2.5×ULN (for liver metastases≤5×ULN);
   4. Creatinine clearance rate (Ccr) ≥60 ml/min.
8. No major organ dysfunction.
9. The patient must agree to provide blood, urine and stool samples for pharmacokinetic studies, and collect them in strict accordance with the required time points and intervals.
10. No mental abnormality, able to understand and undertake informed consent.

Exclusion Criteria:

1. Those who need to receive non-investigative anti-cancer therapy (such as chemotherapy, immunotherapy or biological therapy) during the administration period of this trial.
2. People who are severely allergic to castor oil, or who have had serious adverse reactions to anti-microtubule drugs in the past.
3. Within 4 weeks before receiving treatment, have had any major surgery or suffered major trauma; or are expected to undergo major surgery during the treatment.
4. Pregnancy (positive pregnancy test), breastfeeding patients, or those who are unwilling to use contraception during the test;
5. Those with uncontrollable intracranial hypertension syndrome (persistent headache, short-term blurred vision, and/or diplopia)
6. Combined serious diseases, including severe heart disease, cerebrovascular disease, uncontrolled diabetes, uncontrolled high blood pressure, severe infection, active peptic ulcer, etc.
7. Known HIV infection, or untreated active hepatitis B or C;
8. Known to have alcohol or drug addiction, or have a history of uncontrollable mental illness, lack of legal capacity or limited legal capacity;
9. The investigator believes that it is inappropriate to participate in this trial.
10. Participate in another clinical trial or use other research treatments at the same time.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Utidelone	Drug: Utidelone; 8 patients will be assigned to utidelone arm and receive utidelone injection 30 mg/m2/day intravenously, once a day for 5 consecutive days in a 21-day cycle.
Experimental: Utidelone plus capecitabine	Drug: Utidelone Injection; capecitabine; 8 patients will be assigned to utidelone plus capecitabine arm receiving utidelone plus capecitabine. Utidelone injection 30mg/m2/day, intravenously administered once a day for 5 consecutive days; capecitabine tablets, 1000mg/m2, orally, 2 times a day for 14 consecutive days. 21 days is a cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak Plasma Concentration (Cmax)	To measure the maximal plasma concentration of the study drugs and evaluate the pharmacokinetic characteristics of continuous intravenous administration of utidelone, measure PK parameters such as Maximum Plasma Concentration [Cmax]	12 weeks
C-T curve	To evaluate the pharmacokinetic interaction of utidelone and capecitabine in patients when administered in combination.	12 weeks
Area under the plasma concentration versus time curve (AUC)	To get area under the plasma concentration versus time curve	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure and plot r-t curve	To analyse mass balance	12 weeks
Incidence of treatment-related adverse events as assessed by CTCAE v4.0	To evaluate the safety of the study	6 months

Collaborators and Investigators

• Sponsor: Beijing Biostar Pharmaceuticals Co., Ltd.
• Collaborators: Chengdu Biostar Pharmaceuticals
• Investigators: Principal Investigator: Quchang Ouyang, MD, Hunan Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2020
• Primary Completion (Actual): January 13, 2021
• Study Completion (Actual): February 19, 2021

Study Registration Dates

• First Submitted: May 30, 2021
• First Submitted That Met QC Criteria: September 12, 2021
• First Posted (Actual): September 22, 2021

Study Record Updates

• Last Update Posted (Estimate): January 10, 2023
• Last Update Submitted That Met QC Criteria: January 8, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Capecitabine
• Other Study ID Numbers: BG01-2001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No