Study of Cipatinib in Patients With HER2 Positive or Uncertain Advanced Breast Cancer

This study has been terminated.
Sponsor:
Collaborator:
Chinese Academy of Medical Sciences
Information provided by (Responsible Party):
Jiangsu HengRui Medicine Co., Ltd.
ClinicalTrials.gov Identifier:
NCT01301911
First received: January 28, 2011
Last updated: December 20, 2012
Last verified: December 2012
  Purpose

Cipatinib is an oral tyrosine kinase inhibitor targeting both HER-1 and HER-2 receptors. This study is designed to evaluate the safety and tolerability of cipatinib in patients with HER2 positive or uncertain advanced breast cancer:

  1. To evaluate the safety and tolerability of cipatinib, and the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT)
  2. To determine the pharmacokinetic profile of cipatinib and its metabolites
  3. To assess preliminary antitumor activity
  4. To determine preliminary regimen for phase II study
  5. To determine the relation of expression of HER-1 and HER-2 to the antitumor activity.

Condition Intervention Phase
Breast Cancer
Drug: Cipatinib
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of Cipatinib in Patients With HER2 Positive or Uncertain Advanced Breast Cancer

Resource links provided by NLM:


Further study details as provided by Jiangsu HengRui Medicine Co., Ltd.:

Primary Outcome Measures:
  • The maximum-tolerated dose (MTD) regimen of cipatinib will be defined as the maximum dose level at which no more than one subject out of six experiences a dose-limiting toxicity (DLT) after completing one treatment cycle. [ Time Frame: 3 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Number of participants with adverse events. [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
  • Cipatinib pharmacokinetic parameters may include AUC, Cmax, Tmax, and t1/2. [ Time Frame: 3 weeks ] [ Designated as safety issue: No ]
  • Objective response rate (ORR). [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]

Enrollment: 26
Study Start Date: January 2011
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cipatinib
Each subject will receive a single dose of cipatinib on treatment day 1, followed by 4-day observation period, and then will receive cipatinib once daily in cycles consisting of 21 days.
Drug: Cipatinib
Cipatinib either at 200, 400, 800, 1200, 1400, 1600 or 1800 mg, p.o. once daily

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Aged ≥ 18 and ≤ 65 years.
  • ECOG performance status of 0 to 1.
  • Life expectancy of more than 3 months.
  • Histologically or cytologic confirmed HER2 positive or uncertain advanced breast cancer that is not curable with available therapies.
  • Screening laboratory values within the following parameters:

    • ANC: ≥ 1.5 x 109/L
    • Platelet count: ≥ 100 x 109/L
    • Hemoglobin: ≥ 9.0 g/dL
    • Serum albumin: ≥ 2.5 g/dL
    • Total bilirubin: ≤ 1.5 x upper limit of normal, ULN
    • ALT and AST: ≤ 1.5 x ULN
    • Serum creatinine: ≤ 1.0 x ULN
    • Creatinie clearnce rate: ≥ 50 mL/min
    • Cholesterol≤7.75 mmol/L and triglyceride≤2.5 x ULN
    • LVEF: ≥ 50%
    • QTcF: < 470 ms
  • Recovery from all clinically significant AEs related to prior therapies. Duration from the latest therapy is more than 6 weeks for nitroso or mitomycin, or more than 4 weeks for operation, radiotherapy, cytotoxic agents or molecular targeting.
  • Ability or willingness to swallow tablets, no dysfunction of gastrointestinal absorption.
  • All subjects who are not surgically sterile or postmenopausal must agree and commit to the use of a reliable method of birth control for the duration of the study and for 6 months after the last dose of test article. For women of child bearing potential, a negative urine or serum pregnancy test result before initiating cipatinib.
  • Signed informed consent.

Exclusion Criteria:

  • Subjects with third space fluid that can not be controled by drainage or other methods.
  • Steroid treatment for more than 50 days, or in need of long-term use of steroids.
  • Subjects with uncontrol hypokalemia and hypomagniesemia before study entry.
  • Subjects can not interrupt the using of the drugs that may cause QT prolongation during study.
  • Subjects with meningioma, or with active central nervous system metastases as indicated by clinical symptoms.
  • Subjects with liver metastases which ALT or AST > 1.5 x ULN.
  • Treated or treating with EGFR or HER2 TKIs before study entry.
  • Receiving any other antitumor therapy.
  • Less than 4 weeks from the last clinical trial.
  • Pregnant or breastfeeding women.
  • Known history of hypersensitivity to cipatinib or any of it components.
  • Ongoing infection (determined by investigator).
  • Subjects had any heart disease: coronary artery disease, arrhythmia need to treat, heart failure, LVEF < 50%, and any other heart disease that is determined as unfit for this study by investigator, etc.
  • Evidence of significant medical illness that in the investigator's judgment will substantially increase the risk associated with the subject's participation in and completion of the study. Examples include, but are not limited to, hypertension, severe diabetes, or thyroid disease.
  • Known history of neurological or psychiatric disease, including epilepsy or dementia.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01301911

Locations
China, Beijing
Cancer Institute and Hospital, Chinese Academy of Medical Sciences
Beijing, Beijing, China, 100021
Sponsors and Collaborators
Jiangsu HengRui Medicine Co., Ltd.
Chinese Academy of Medical Sciences
  More Information

No publications provided

Responsible Party: Jiangsu HengRui Medicine Co., Ltd.
ClinicalTrials.gov Identifier: NCT01301911     History of Changes
Other Study ID Numbers: XPTN-Ia-1.0
Study First Received: January 28, 2011
Last Updated: December 20, 2012
Health Authority: China: Food and Drug Administration

Keywords provided by Jiangsu HengRui Medicine Co., Ltd.:
Breast cancer, Advanced
Cipatinib
phase I
HER2 positive or uncertain advanced breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms
Neoplasms by Site
Skin Diseases

ClinicalTrials.gov processed this record on October 30, 2014