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RC48-ADC Administered Intravenously to Subjects With HER2-Positive in Advanced Breast Cancer

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ClinicalTrials.gov Identifier: NCT03052634
Recruitment Status : Recruiting
First Posted : February 14, 2017
Last Update Posted : February 23, 2017
Sponsor:
Information provided by (Responsible Party):
RemeGen

Brief Summary:
A significance,safety and pharmacokinetic of open-label and multicentric Phase Ib/II Study of RC48-ADC Administered Intravenously to Subjects With HER2-Positive in Advanced Breast Cancer

Condition or disease Intervention/treatment Phase
Advanced Breast Cancer Drug: RC48-ADC Drug: Lapatinib plus capecitabine Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 165 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: The Intervention Model of phase Ib is single group assignment,however ,The Intervention Model of phase II is parallel group assignment.The Experimental of The phase II is RC48-ADC, and the active comparator of RC48-ADC is lapatinib plus capecitabine
Masking: None (Open Label)
Primary Purpose: Treatment
Study Start Date : November 2016
Estimated Primary Completion Date : January 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: RC48-ADC

Phase Ib: Patients will receive RC48-ADC 1.5 mg/kg or 2.0mg/kg or 2.5mg/kg intravenously (IV) administered once every 2 weeks.

Phase II: Patients will receive a suitable RC48-ADC dose which was selected according to the Ib phase of the experimental results RC48-ADC via IV administered once every 2 weeks.

Drug: RC48-ADC
Other Name: ADC=Antibody-drug conjugates

Active Comparator: Lapatinib plus capecitabine

Phase II: Active Comparator:Lapatinib+capecitabine Lapatinib repeating dose taken orally every day for 3 weeks as a treatment cycle.

Capecitabine :1000 mg/m2 bid, oral. Days: 1-14 every three weeks.

Drug: Lapatinib plus capecitabine



Primary Outcome Measures :
  1. Progression Free Survival (PFS) [ Time Frame: Estimated 2 year ]
    Progression-free survival (PFS) was defined as the time from the first day of study treatment (Day 1) to first documented disease progression or death, whichever occurred first. If a patient did not experience disease progression or die, PFS was censored at the day of the last tumor assessment that a patient was known to be progression free.


Secondary Outcome Measures :
  1. Cmax [ Time Frame: Estimated 2 year ]
    Maximum Observed Plasma Concentration

  2. AUC [ Time Frame: Estimated 2 year ]
    Area Under Curve

  3. Tmax [ Time Frame: Estimated 2 year ]
    Time for Cmax

  4. Overall response Rate (ORR) [ Time Frame: Estimated 2 year ]
    As per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 - to estimate the anti-tumor activity of RC48-ADC.

  5. Clinical Benefit Rate (CBR) [ Time Frame: Estimated 2 year ]
    Clinical Benefit Rate was defined as the percentage of patients with complete remission (CR) partial remission (PR) stable (SD) not less than 4 months.



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Signed informed consent form;
  • Aged 18-70 years;
  • Eastern Cooperative Oncology Group(ECOG) physical condition is 0 or 1;
  • Life expectancy greater than 12 weeks;
  • Confirmed by histology or cytology,the patients who are HER2- positive, locally advanced or metastatic breast cancer,and who perform as having no effect on standard therapy (disease progression after treatment or treatment free remission) or intolerant of standard treatment or can not accept the standard treatment .
  • Patients with locally advanced or metastatic advanced breast cancer diagnosed by pathology and refractory to standard of care therapy, or for whom no standard of care therapy is available histology standard of care therapy, or for whom no standard of care therapy is available;
  • Documented Human epidermal growth factor receptor 2 (HER2)-positive as measured either by immunohistochemistry (IHC 2+ and by fluorescence in situ hybridization (FISH)or by immunohistochemistry (score, 3+) ;
  • Patients with measurable and appreciable tumor lesions according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1)
  • Adequate organ function as defined by the following criteria:

    (1)absolute neutrophil count(ANC) >= 1.5 x 10(9)/L; (2) platelets>=100*10(9)/L; (3)Total serum bilirubin <=1.5*ULN; (4)serum aspartate transaminase (AST)and serum alanine transaminase (ALT) <=2.5*upper limit of normal (ULN), or AST and ALT<=5*ULN if liver function abnormalities are due to underlying malignancy; (5) Serum creatinine clearance rate >= 45 mL/min; (6)international normalized ratio(INR) and activated partial thromboplastin time (aPTT) must be less than or equal to 1.5 times the upper limit of the normal range (ULN);

  • Women of child-bearing potential and men must agree to use adequate contraception (e.g., condoms, implants, injectables, combined oral contraceptives, some intrauterine devices, complete sexual abstinence, or sterilized partner) prior to study entry and during the period of therapy and for 30 days after the last dose of study drug.
  • Left ventricular ejection fraction (LVEF) >= 50% as assessed by echocardiogram.

Exclusion Criteria:

  • Current pregnancy or lactation.
  • The patient received anticancer therapy within 4 weeks before study drug treatment;, including chemotherapy, radiotherapy, surgery or hormone therapy, molecular targeted therapy (including trastuzumab so on ), using Trastuzumab emtansine(T-DM1) clinical study or participating in the clinical trial of the drug analogues.
  • The patient have third interstitial fluid (a large number of pleural effusion or ascites) which is clinical symptom or can not be controlled by drainage or other methods;
  • Received Palliative radiation therapy for bone metastases within 2 weeks before study drug treatment;
  • Unresolved toxicities from prior anti-cancer therapy, defined as having not resolved to Common Terminology Criteria for Adverse Event (CTCAE, version 4), grade less than or equal to1, or to the levels dictated in the inclusion/exclusion criteria with the exception of alopecia;
  • Participated in clinical drug studies within 4 weeks;
  • known hypersensitivity or delayed hypersensitivity to the some components of RC48-ADC or similar drugs;
  • the active infection with clinical significance according to the researcher's judgment,
  • Known history of immune deficiency,including HIV-positive or other known acquired or congenital immunodeficiency, or organ transplantation;
  • Unwilling or unable to participate in all required study evaluations and procedures.
  • Serious complications such as diabetes ,interstitial pneumonia ,pulmonary fibrosis,hypertension and Acute lung disease;
  • there are a variety of factors affecting medication intake and absorption such as unable to swallow, chronic diarrhea or intestinal obstruction;
  • un-controlled primary or metastatic tumor of brain;
  • Patients who had received systemic steroid therapy for a long time(Patients who had received systemic steroid therapy for short time and stopped drug more than 2 weeks could be enrolled );
  • Preexisting peripheral neuropathy ≥ grade 2;
  • History of nerve or psychiatric disorders;
  • Cardiovascular disease problems includingAcute myocardial infarction, unstable angina, or myocardial infarction, stroke, transient ischemic attack or New York Heart Association (NYHA) grade 2 or more (including 2) of congestive heart failure within the last 6 months.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03052634


Contacts
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Contact: Lin Li 86-010-58075563 hnanlilin@163.com

Locations
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China, Beijing
Cancer Hospital Chinese Academy of Medical Sciences Recruiting
Beijing, Beijing, China, 100021
Sponsors and Collaborators
RemeGen

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Responsible Party: RemeGen
ClinicalTrials.gov Identifier: NCT03052634     History of Changes
Other Study ID Numbers: C003 CANCER
First Posted: February 14, 2017    Key Record Dates
Last Update Posted: February 23, 2017
Last Verified: December 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Capecitabine
Lapatinib
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors