Clinical Trials /

Study of RC48-ADC in Patients With HER2-Positive Advanced Malignant Solid Tumors

NCT02881138

Description:

A tolerance, safety and pharmacokinetic ascending dose Phase I Study of RC48-ADC Administered Intravenously to Subjects With HER2-Positive malignant in Advanced Malignant solid Tumors.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of RC48-ADC in Patients With HER2-Positive Advanced Malignant Solid Tumors
  • Official Title:

Clinical Trial IDs

  • ORG STUDY ID: C001 CANCER
  • NCT ID: NCT02881138

Conditions

  • Solid Tumors

Interventions

DrugSynonymsArms
RC48-ADCRC48-ADC

Purpose

A tolerance, safety and pharmacokinetic ascending dose Phase I Study of RC48-ADC Administered Intravenously to Subjects With HER2-Positive malignant in Advanced Malignant solid Tumors.

Trial Arms

NameTypeDescriptionInterventions
RC48-ADCExperimentalThe phase I component has several dose levels of RC48-ADC (0.5 mg/kg, 1.0mg/kg, 1.5mg/kg, 2.0mg/kg, 2.5mg/kg, 3.0mg/kg, 3.5mg/kg, 4.0 mg/kg and 4.5 mg/kg) and is designed as a traditional dose-escalation study.Determine the recommended Phase II doses and regimens of RC48-ADC. Dosing interval is once two weeks.
  • RC48-ADC

Eligibility Criteria

        Inclusion Criteria:

          -  Signed informed consent form;

          -  Aged 18-65 years;

          -  ECOG physical condition is 0 or 1;

          -  Life expectancy greater than 12 weeks;

          -  Patients with locally advanced or metastatic malignant solid tumors 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:

               -  absolute neutrophil count(ANC) >= 1.5 x 10(9)/L;

               -  platelets>=70*10(9)/L;

               -  Total serum bilirubin <=1.5*ULN;

               -  serum aspartate transaminase (AST) and serum alanine transaminase (ALT)
                  <=3.0*upper limit of normal (ULN), or AST and ALT<=5*ULN if liver function
                  abnormalities are due to underlying malignancy;

               -  normal serum creatinine ;

               -  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 [IUDs], 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;

          -  Major surgery within 4 weeks of first dose of study drug and not fully recovered

          -  receiving palliative radiation therapy for bone metastases if administered <= 2 weeks
             prior to first study 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;

          -  Prior-treatment with clinical research anticancer drugs within 28 days before study
             drug treatment;

          -  Participated in clinical drug studies within 4 weeks;

          -  receiving antineoplaston therapy including chemotherapy or radiotherapy , hormonal
             cancer therapy,biological therapy or immunotherapy within 4 weeks of starting study
             treatment,but excepting for the following treatment:

               -  aiming at treatment of prostate cancer by gonadotropin releasing hormone (GnRH)
                  antagonist ;

               -  Hormone replacement therapy;

          -  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;

          -  Currently active clinically significant cardiovascular disease such as uncontrolled
             arrhythmia, congestive heart failure, or greater than or equal to Class 2 congestive
             heart failure as defined by the New York Heart Association Functional Classification,
             or history of myocardial infarction unstable angina, or acute coronary syndrome within
             6 months prior to enrollment in the study;

          -  Unwilling or unable to participate in all required study evaluations and procedures;

          -  the time interval which is from the last chemotherapy or HER2 targeted therapy until
             the first trial is more than 21 days;

          -  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);

          -  Serious complications such as diabetes, interstitial pneumonia, pulmonary fibrosis,
             hypertension and Acute lung disease;

          -  Patients using trastuzumab in the 60 days before the experiments;

          -  Uncontrolled primary or metastatic tumor of brain;

          -  Current peripheral neuropathy of Grade ≥ 2;

          -  History of nerve or psychiatric disorders.
      
Maximum Eligible Age:65 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:maximal tolerance dose (MTD) of RC48-ADC
Time Frame:DLT will be evaluated on Day 21 during cycle 1
Safety Issue:
Description:The dose level in which >= 2 out of 6 patients have dose-limiting toxicity (DLT). The MTD is defined as the previous dose level.

Secondary Outcome Measures

Measure:Safety (the drug safety as assessed by NCI-CTCAE v4.0)
Time Frame:Up to 1 years
Safety Issue:
Description:The drug safety as assessed by NCI-CTCAE v4.0

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:RemeGen

Last Updated

July 31, 2017