Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Combination of HX008 And Niraparib in GErm-line-mutAted Metastatic Breast Cancer (CHANGEABLE)

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: NCT04508803
Recruitment Status : Not yet recruiting
First Posted : August 11, 2020
Last Update Posted : August 11, 2020
Sponsor:
Information provided by (Responsible Party):
Jian Zhang,MD, Fudan University

Tracking Information
First Submitted Date  ICMJE August 9, 2020
First Posted Date  ICMJE August 11, 2020
Last Update Posted Date August 11, 2020
Estimated Study Start Date  ICMJE September 1, 2020
Estimated Primary Completion Date February 20, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 9, 2020)
Overall Response Rate (ORR) [ Time Frame: Up to approximately 12 weeks ]
ORR is the percentage of participants with the best overall response of complete response (CR) or partial response (PR) according to RECIST 1.1. CR = Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm; PR = At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: August 9, 2020)
  • Overall Survival (OS) [ Time Frame: Up to approximately 30 months ]
    Time from date of randomization to the date of death from any cause
  • Progression-Free Survival (PFS) [ Time Frame: Up to approximately 30 months ]
    PFS defined as the time from the date of randomization to the first evidence of disease progression as defined by response evaluation criteria in solid tumors (RECIST) v1.1 or death from any cause. Progressive Disease (PD) was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. If a participant does not have a complete baseline disease assessment, then the PFS time was censored at the date of randomization, regardless of whether or not objectively determined disease progression or death has been observed for the participant. If a participant was not known to have died or have objective progression as of the data inclusion cutoff date for the analysis, the PFS time was censored at the last adequate tumor assessment date.
  • Clinical Benefit Rate (CBR) [ Time Frame: Up to approximately 12 weeks ]
    Percentage of participants with complete response (CR) or partial response (PR) or stable disease (SD) lasting 24 weeks or longer as defined in RECIST 1.1.CR = Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to < 10 mm; PR = At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters; SD = Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease: PD = At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20% the sum must also demonstrate an absolute increase of at least 5 mm.
  • Duration of Response (DOR) [ Time Frame: Up to approximately 10 months ]
    Time from the first documented response (CR or PR) to the first documented progression or death due to underlying cancer
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Combination of HX008 And Niraparib in GErm-line-mutAted Metastatic Breast Cancer
Official Title  ICMJE Combination of HX008 And Niraparib in GErm-line-mutAted Metastatic Breast Cancer: a muLti-centEr Phase II Study
Brief Summary A number of anti-PD-1/L1 monoclonal antibodies have been approved for the treatment of various advanced tumors in the world, and many studies on anti-PD-1 /L1 monoclonal antibodies for breast cancer are also being carried out. HX008 (Taizhou Hanzhong Biomedical Co., Ltd.China) combined gemcitabine and cisplatin (GP) regimen for first-line treatment of advanced triple negative breast cancer has been shown good efficacy. On the other hand,HRD as the target of PARP inhibitor therapy in the treatment of breast cancer has a broad prospect, In HRD tumor patients, the use of PARPi can make obstacles of DNA damage repair(DDR), accumulation of DNA damage, thus promote the apoptosis of tumor cells. Several PARPi have been approved worldwide (including Olaparib, Rucaparib, Niraparib, Talazoparib, Veliparib) for the treatment of ovarian and/or breast cancer. Theoretically, PARPi and anti-PD-1 monoclonal antibody can play a synergistic mechanism. In this study, HX008 combined with Niraparib is designed to treat metastatic breast cancer patients with DDR gene (BRCA1/2, PALB2, CHEK2, ATM, ATR, BAP1, BARD1, BLM, BRIP1, CHEK1, CDK12, FANCA, FANCC, FANCD2, FANCE, FANCF, FANCM, MRE11A, NBN, PTEN, RAD50, RAD51C, RAD51D, WRN) pathogenic/suspected pathogenic germline mutation, so as to explore the possibility of more combined therapy for breast cancer to achieve better therapeutic effect.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Treatment Efficacy
Intervention  ICMJE
  • Drug: HX008,Niraparib
    Subjects received intravenous HX008 at a fixed dose of 200mg, administered every 3 weeks, and 200mg of Niraparib orally per day.Every 3 weeks is a cycle.
  • Drug: HX008,Niraparib,Trastuzumab
    Subjects received intravenous HX008 at a fixed dose of 200mg once every 3 weeks; 200mg Niraparib orally per day;Trastuzumab 8mg/kg in the first cycle and 6mg/kg after the first cycle intravenously once every 3 weeks; Every 3 weeks is a cycle.
  • Drug: HX008,Niraparib,Pyrrolitinib

    HER-2 negative subjects received intravenous HX008 at a fixed dose of 200mg, administered every 3 weeks, and 200mg of Neirapali orally per day. Every 3 weeks is a cycle.

    Her-2 positive subjects received intravenous HX008 at a fixed dose of 200mg once every 3 weeks; 200mg Niraparib orally per day; Pyrrolitinib is taken orally at 400mg per day; Every 3 weeks is a cycle.

Study Arms  ICMJE
  • Experimental: The main research
    Patients diagnosed with HER2 negative metastatic breast cancer with BRCA1/2, PALB2, CHEK2 pathogenic/suspected pathogenic germline mutation are recruited.
    Intervention: Drug: HX008,Niraparib
  • Experimental: Ancillary Exploration research 1
    Patients diagnosed with HER2 negative metastatic breast cancer with DDR gene (include ATM、ATR、BAP1、BARD1、BLM、BRIP1、CHEK1、CDK12、FANCA、FANCC、FANCD2、FANCE、FANCF、FANCM、MRE11A、NBN、PTEN、RAD50、RAD51C、RAD51D、WRN)pathogenic/suspected pathogenic germline mutation except BRCA1/2, PALB2 and CHEK2 are recruited.
    Intervention: Drug: HX008,Niraparib
  • Experimental: Ancillary Exploration research 2
    Patients diagnosed with HER2 positive metastatic breast cancer with DDR gene pathogenic/suspected pathogenic germline mutation are recruited.
    Intervention: Drug: HX008,Niraparib,Trastuzumab
  • Experimental: Ancillary Exploration research 3
    Patients diagnosed with brain metastases breast cancer with DDR gene pathogenic/suspected pathogenic germline mutation who has not undergone or progressed after brain radiotherapyare recruited.
    Intervention: Drug: HX008,Niraparib,Pyrrolitinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: August 9, 2020)
50
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 28, 2022
Estimated Primary Completion Date February 20, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Performance Status 0-1.
  2. Life expectancy longer than 3 months.
  3. Histological proven unresectable recurrent or advanced breast cancer.
  4. For ehe main research: Patients with histopathologically diagnosed advanced (recurrent or metastatic) HER2-negative breast cancer with definite pathogenic/suspected pathogenic germline mutations in BRCA1/2, or PALB2, or CHEK2.
  5. For ancillary exploration research 1: Patients with histopathologically diagnosed advanced (recurrent or metastatic) HER2-negative breast cancer with definite pathogenic/suspected pathogenic germline mutations in ATM, or ATR, or BAP1, or BARD1, or BLM, or BRIP1, or CHEK1, or CDK12, or FANCA, or FANCC, or FANCD2, or FANCE, or FANCF, or FANCM, or MRE11A, or NBN, or PTEN, or RAD50, or RAD51C, or RAD51D, or WRN.
  6. For ancillary exploration research 2: Patients with histopathologically diagnosed advanced (recurrent or metastatic) HER2-positive breast cancer with definite pathogenic/suspected pathogenic germline mutations in BRCA1/2, or PALB2, or CHEK2, or ATM, or ATR, or BAP1, or BARD1, or BLM, or BRIP1, or CHEK1, or CDK12, or FANCA, or FANCC, or FANCD2, or FANCE, or FANCF, or FANCM, or MRE11A, or NBN, or PTEN, or RAD50, or RAD51C, or RAD51D, or WRN.
  7. For ancillary exploration research 3: Patients with histopathologically diagnosed advanced (recurrent or metastatic) breast cancer with brain and with metastases definite pathogenic/suspected pathogenic germline mutations in BRCA1/2, or PALB2, or CHEK2, or ATM, or ATR, or BAP1, or BARD1, or BLM, or BRIP1, or CHEK1, or CDK12, or FANCA, or FANCC, or FANCD2, or FANCE, or FANCF, or FANCM, or MRE11A, or NBN, or PTEN, or RAD50, or RAD51C, or RAD51D, or WRN.
  8. Not more than 2 - line chemotherapy regimens were received in the stage of recurrence and metastasis.Platinum-based or PARP1 inhibitor treatment may be accepted, but the patient must have no disease progression during or within 8 weeks of the end of platinum-based or PARP1 inhibitor treatment at the stage of recurrence and metastasis, and relapse within 12 months after the end of neoadjuvant/adjuvant therapy.
  9. Patients with hormone-receptor-positive, HER2 negative must received at least first-line endocrine therapy and progress to the stage of recurrence or metastasis, or have disease recurrence or metastasis during adjuvant endocrine therapy or within 1 year after the end of adjuvant therapy.
  10. At least one extracranial measurable disease according to the response evaluation criteria in solid tumor (RECIST 1.1).
  11. All patients enrolled are required to have adequate hematologic, hepatic, and renal function
  12. Women of childbearing age must have a pregnancy test (serum or urine) that is negative within 7 days of enrollment, and be willing to use an appropriate method of contraception during the study and 8 weeks after the last dose of the study drug.
  13. Be able to understand the study procedures and sign informed consent.

Exclusion Criteria:

  1. Pregnant or lactating women.
  2. Treatment with an investigational product within 4 weeks before the first treatment.
  3. Subjects have any active autoimmune disease, history of autoimmune disease, or history of disease or syndrome requiring systemic steroid or immunosuppressive medication.
  4. Subjects had a history of immunodeficiency, including HIV positive, or other acquired or congenital immunodeficiency disorders.
  5. Received chemotherapy, radiotherapy, targeted therapy and major surgery within 3 weeks before the first administration;Received endocrine therapy within 2 weeks prior to first administration.
  6. Uncontrolled serious infection.
  7. Patients with hypertension and uncontrolled hypertension with hypotensive drugs therapy (systolic blood pressure > 140 mmHg, diastolic blood pressure > 90 mmHg). Patients with grade I or above myocardial ischemia or myocardial infarction or arrhythmia (including QT interval ≥ 440 ms) or cardiac insufficiency.
  8. Inability to swallow, gastrointestinal resection, chronic diarrhea and obstruction of the intestine, various factors which affect drug use and absorption.
  9. Patients with active viral hepatitis B or C.
  10. Patients with chronic obstructive pulmonary disease (COPD), or pulmonary fibrosis.
  11. Have received prior treatment with anti-PD-1/PD-L1 drugs and PARP inhibitors;
  12. Patient who has a history of psychotropic substance abuse and is unable to stop or have a history of mental disorders.

    -

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jian Zhang, MD,PhD +8664175590 ext 85000 syner2000@163.com
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04508803
Other Study ID Numbers  ICMJE CHANGEABLE
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Jian Zhang,MD, Fudan University
Study Sponsor  ICMJE Fudan University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jian Zhang, MD,PhD Fudan University
PRS Account Fudan University
Verification Date August 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP