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A Study of RC48-ADC Administered Intravenously to Patients With HER2-Positive Metastatic Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03500380
Recruitment Status : Recruiting
First Posted : April 18, 2018
Last Update Posted : January 7, 2020
Sponsor:
Information provided by (Responsible Party):
RemeGen

Brief Summary:
This is a Phase II, randomized, multicenter, 2-arm, open-label clinical trial designed to compare the safety and efficacy of RC48-ADC with that of capecitabine + lapatinib in participants with human epidermal growth factor receptor 2 (HER2)-positive locally advanced or metastatic breast cancer. Participants will be treated until disease progression (PD), unmanageable toxicity, or study termination. Once disease progression is reported, all participants will be followed for survival every 3 months until death, loss to follow-up, withdrawal of consent, or study termination.

Condition or disease Intervention/treatment Phase
Breast Neoplasms Breast Diseases Capecitabine HER2-positive Breast Cancer HER2 Positive Breast Carcinoma Drug: RC48-ADC Drug: Lapatinib Drug: Capecitabine Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 228 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized, Multicenter, Phase II Study of the Efficacy and Safety of Recombinant Humanized Anti-HER2 Monoclonal Antibody-MMAE Conjugate For Injection in Patients With HER2-Positive Locally Advanced or Metastatic Breast Cancer
Actual Study Start Date : April 24, 2018
Estimated Primary Completion Date : July 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
Participants will receive RC48-ADC 2.0 mg/kg intravenous (IV) infusion each 14-day treatment cycle until disease progression (PD) (as assessed by the investigator), unmanageable toxicity, or study termination.
Drug: RC48-ADC
RC48-ADC 2.0 mg/kg IV every 14 days
Other Name: RC48

Active Comparator: Lapatinib + Capecitabine
Participants will receive lapatinib 1250 mg orally once daily during each 21-day cycle + capecitabine 2000 mg/m^2 orally daily on Days 1-14 of each 21-day treatment cycle until PD (as assessed by the investigator), unmanageable toxicity, or study termination.
Drug: Lapatinib
Lapatinib 1250 mg orally once daily during each 21-day cycle.

Drug: Capecitabine
Capecitabine 2000 mg/m^2 orally daily on Days 1-14 of each 21-day treatment cycle.




Primary Outcome Measures :
  1. Progression-free Survival (PFS) as Assessed by an IRC [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months ]
    Tumor response was assessed by an IRC according to RECIST v1.1.


Secondary Outcome Measures :
  1. Progression-free Survival (PFS) as Assessed by Investigator [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months ]
    Tumor response was assessed by investigator according to RECIST v1.1.

  2. Objective Response Rate (ORR) [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months ]
    Objective Response Rate was defined as the percentage of participants with a complete response (CR) or partial response (PR).

  3. Duration of Objective Response (DOR) [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months ]
    DOR was defined as the time from first documented OR to first documented PD or death from any cause, whichever occurred earlier.

  4. Clinical Benefit Rate (CBR) [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months ]
    Participants were considered as experienced clinical benefit if they had an OR or maintained stable disease (SD) for at least 6 months from randomization. OR: CR or PR determined on 2 consecutive tumor assessments >/=4 weeks apart.

  5. Time to Treatment Failure [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months ]
    Time to treatment failure was defined as the time from randomization to discontinuation of treatment for any reason, including PD (per investigator review), treatment toxicity, or death from any cause.

  6. Overall Survival [ Time Frame: From date of randomization until the date of death from any cause, assessed up to 48 months ]
    OS was defined as the time from the date of randomization to the date of death from any cause.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


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

Inclusion Criteria:

  • Voluntary agreement to provide written informed consent.
  • Age ≥ 18 years and ≤ 70 years.
  • Predicted survival ≥ 3 months.
  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
  • All female subjects will be considered to be of child-bearing potential unless they are postmenopausal, or have been sterilized surgically. Female subjects of child-bearing potential must agree to use two forms of highly effective contraception. Male subjects and their female partner who are of child-bearing potential must agree to use two forms of highly effective contraception.
  • Willing to adhere to the study visit schedule and the prohibitions and restrictions specified in this protocol.
  • Adequate organ function, evidenced by the following laboratory results:

Hemoglobin ≥ 9.0 g/dL; Absolute neutrophil count ≥ 1500 cells/mm3 Hemoglobin ≥ 9.0 g/dL Total bilirubin ≤ 1.5× ULN AST, ALT, and ALP ≤ 2.5× ULN and ≤ 5 x ULN with hepatic metastasis; Serum creatinine ≤1╳ULN or creatinine clearance≥ 60ml/min (Cockcroft-Gault equation) or 24-hour urine creatinine clearance≥ 60ml/min.

Cardiac ejection fraction ≥ 50 %.

  • Histologically or cytologically confirmed invasive breast cancer: incurable, unresectable, locally advanced breast cancer or MBC.
  • HER2-positive (defined as IHC 3+ or gene-amplified by FISH).
  • Prior treatment for breast cancer in the neoadjuvant, adjuvant, unresectable, locally advanced, or metastatic setting must include taxane, alone or in combination with another agent.
  • Prior treatment for breast cancer in the adjuvant, unresectable, locally advanced, or metastatic setting must include trastuzumab, alone or in combination with another agent.
  • Documented progression of incurable unresectable, locally advanced, or metastatic breast cancer, defined by the investigator: Progression must occur during or after most recent treatment for locally advanced/MBC or within 6 months after completing adjuvant therapy.
  • Prior treatment for breast cancer in the locally advanced, or metastatic setting must include 1-2 lines of systemic chemotherapy.
  • Measurable disease according to RECIST 1.1.

Exclusion Criteria:

  • Current severe, uncontrolled systemic disease (e.g., clinically significant diabetes, hypertension, pulmonary disease).
  • Currently known active infection with HIV or tuberculosis.
  • Has known active liver disease ( e.g., Hepatitis B virus/ Hepatitis C virus or liver cirrhosis).
  • Presence of conditions that could affect gastrointestinal absorption: malabsorption syndrome, resection of the small bowel or stomach, and ulcerative colitis.
  • History of treatment with other investigational drug within 4 weeks of planned start of trial treatment.
  • History of major surgery within 4 weeks of planned start of trial treatment.
  • Has received a live virus vaccine within 4 weeks of planned start of trial treatment.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Has a history of severe hypersensitivity reaction to study drug.
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
  • Pregnancy or lactation.
  • Assessed by the investigator to be unable or unwilling to comply with the requirements of the protocol.
  • known central nervous system metastases.
  • History of other malignancy within the previous 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, or cancers with a similar curative outcome as those mentioned above.
  • Subjects who have not recovered from acute toxicities as a result of prior anti-cancer therapy to ≤ Grade 1, according to Common Terminology Criteria for Adverse Events (CTCAE), except for alopecia.
  • History of receiving any anti-cancer drug/biologic treatment within 4 weeks prior to trial treatment except hormone therapy, which could be given up to 7 days.
  • History of receiving any Chinese drug within 7 days prior to trial treatment.
  • History of receiving any HER2-target drug.
  • History of receiving capecitabine within 6 months prior to trial treatment or intolerable to capecitabine.
  • Known hypersensitivity to 5-fluorouracil or known dihydropyrimidine dehydrogenase deficiency.
  • History of receiving t-dm1.
  • History of radiation therapy within 14 days of trial treatment.

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): NCT03500380


Contacts
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Contact: Jianmin Fang +8610-58075763 jianminfang@hotmail.com

Locations
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Sponsors and Collaborators
RemeGen
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Responsible Party: RemeGen
ClinicalTrials.gov Identifier: NCT03500380    
Other Study ID Numbers: RC48-C006
First Posted: April 18, 2018    Key Record Dates
Last Update Posted: January 7, 2020
Last Verified: January 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Breast Neoplasms
Breast Diseases
Neoplasms by Site
Neoplasms
Skin Diseases
Capecitabine
Lapatinib
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors