search
Back to results

A Multi-cohort Phase II Study of HER2-positive and Triple-negative Breast Cancer Brain Metastases.

Primary Purpose

Breast Cancer

Status
Unknown status
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Pyrotinib
Temozolomide Injection
SHR-1316
Bevacizumab
Cisplatin/Carboplatin
Sponsored by
Fudan University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Cancer

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Age ≥ 18 years old, and ≤ 70 years old, both genders;
  2. ECOG performance status 0-2;
  3. Pathological tests confirm HR-negative / HER2-positive or HR-negative / HER2-negative breast cancer;there is evidence of local recurrence or metastasis;not suitable with curative surgery or radiation therapy;HR negative is defined as: ER-negative and PR-negative, the proportion of positively stained tumor cells in all tumor cells is <1%;HER2-positive is defined as: Immunohistochemical detection of HER2 (3+) or fluorescence in situ hybridization (FISH) detection result is positive;
  4. Patients with HER2 + breast cancer who have previously received trastuzumab and taxanes; For TNBC, it is required that no platinum drugs have been used before, or platinum drugs have been used (cisplatin/carboplatin only one regimen) and platinum sensitive: no progression during at least 4 cycles of treatment, more than 3 month period between last platinum regimen and the progression of disease;
  5. MRI confirmed brain metastases, at least one intracranial parenchymal metastatic lesion with a longest diameter ≥ 1.0 cm without prior radiotherapy;
  6. Mannitol or steroid hormone therapy is allowed before enrollment, but the dose of steroid hormone should be stable for at least one week;
  7. Adequate function of major organs meets the following requirements:

(1)Blood routine

  • ANC≥1.5×109/L;
  • PLT≥75×109/L;
  • Hb≥90 g/L(Allows blood transfusion or the use of medication to ensure that the content of hemoglobin) (2)Coagulation: INR≤1.5,APTT≤1.5×ULN, PT does not exceed the upper limit of normal (3)Blood biochemistry
  • TBIL≤1.5 × ULN;
  • ALT and AST≤3 × ULN (liver metastasis≤5.0 × ULN);
  • Urea nitrogen ≤ 1.5 × ULN;
  • Cr≤1.5 × ULN or creatinine clearance ≥50 mL / min (Cockcroft-Gault formula) (4)Cardiac ultrasound: LVEF≥50%; (5)12-lead ECG: females QTcF interval <470msec and males <450ms; 8.Willing to join the study, sign informed consent, have good compliance and cooperate with follow-up.

Exclusion Criteria:

  1. Leptomeningeal or cystic metastases confirmed by MRI or lumbar puncture.
  2. Presence of third interstitial fluid that cannot be controlled by drainage or other methods (e.g., a large amount of pleural effusion and ascites);
  3. Suffering from gastrointestinal diseases such as intestinal obstruction, peptic ulcer or active bleeding, which affects the taking and absorption of drugs;
  4. Whole brain radiotherapy, chemotherapy or surgery within 14 days prior to enrollment. Has received prior therapy with trastuzumab within the previous week;
  5. Subjects with HR+/HER2- who has received prior therapy with temozolomide. Subjects with HR-/HER2- who has received prior therapy with bevacizumab or PD-1/PD-L1;
  6. Any previous or concurrent treatment with Anti-HER2 TKIs;
  7. Participation in any other clinical trials within 2 weeks of enrollment;
  8. Concurrent use of any other Anti-cancer drugs;
  9. Other malignancies within 5 years, except cured in-situ of uterine cervix carcinoma , skin basal cell carcinoma and squamous-cell carcinoma;
  10. History of heart disease: (1) Arrhythmias requiring medical treatment or clinical significance, (2) Myocardial infarction, (3) Heart failure, (4)Any heart diseases that investigator believes not suitable for this study;
  11. History of allergy or hypersensitivity to any of the study drugs or study drug components;
  12. History of immunodeficiency including HIV-positive, active hepatitis B/C, other acquired, congenital immunodeficiency disease or history of organ transplantation;
  13. A clear history of neurological or mental disorders, including epilepsy or dementia;
  14. Pregnant or breastfeeding women. Women of childbearing potential who have a positive pregnancy test or unwilling to use adequate contraception prior to enrollment and for the duration of study participation;
  15. According to the investigator's judgment, there is a concomitant disease that seriously endangers the safety of subjects or affects the completion of the study (including but not limited to severe hypertension, severe diabetes, active infection, thyroid disease that cannot be controlled by drugs);
  16. Any condition which in the investigator's opinion makes the subjects unsuitable for the study participation.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Experimental

    Arm Label

    Cohort HR+/HER2+

    Cohort HR-/HER2-

    Arm Description

    Hormone receptor negative, HER2 positive participants will receive Pyrotinib in combination with Temozolomide until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.

    Hormone receptor negative, HER2 negative participants will receive SHR1316 in combination with bevacizumab plus cisplatin or carboplatin until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.

    Outcomes

    Primary Outcome Measures

    Overall Response Rate in the CNS
    CNS ORR will be assessed by the investigator according to RANO-BM criteria. According to these criteria Complete Response (CR) will be defined as the disappearance of all CNS target lesions sustained for at least 4 weeks; no new lesions, no corticosteroids; stable or improved clinically. Partial Response (PR) will be defined as a decrease of at least 30% in the sum longest diameter (LD) of CNS target lesions, taking as reference the baseline sum LD, sustained for at least 4 weeks; no new lesions; no corticosteroids; stable or improved clinically.

    Secondary Outcome Measures

    Clinical Benefit Rate in the CNS
    CNS clinical benefit rate (CBR) will be defined as the percentage of patients who experience a CR, PR or Stable Disease (SD) for at least 24 weeks.
    Progression-free survival
    PFS will be defined as the time from the first dose of treatment to death or disease progression.
    Overall survival
    OS will be defined as the time from the first dose of treatment to death for any cause.
    First progression site
    The first lesion to progress.
    Safety as assessed by percentage of patients with any Adverse Event
    Adverse event according to NCI-CTC AE 5.0

    Full Information

    First Posted
    February 24, 2020
    Last Updated
    March 9, 2020
    Sponsor
    Fudan University
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT04303988
    Brief Title
    A Multi-cohort Phase II Study of HER2-positive and Triple-negative Breast Cancer Brain Metastases.
    Official Title
    A Prospective, Single-arm, Single-center, Multi-cohort Phase II Clinical Study of HER2-positive and Triple-negative Breast Cancer Brain Metastases
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    March 2020
    Overall Recruitment Status
    Unknown status
    Study Start Date
    March 30, 2020 (Anticipated)
    Primary Completion Date
    December 30, 2021 (Anticipated)
    Study Completion Date
    January 30, 2022 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Fudan University

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No

    5. Study Description

    Brief Summary
    The study is being conducted to assess the effectiveness and safety of treatment options for breast cancer brain metastases based on molecular typing.
    Detailed Description
    This is a prospective, single-arm, single-center, two cohorts, Simon's two-stage design, phase II clinical trial in HER2-positive and triple-negative breast cancer brain metastases patients. Subjects will be divided into two cohorts by hormone receptor status and HER2 status. HER2+/HR- subjects will enter Cohort A to receive pyrotinib plus temozolomide; HER2-/HR- subjects will enter Cohort B to receive bevacizumab, SHR1316 combined with cisplatin/carboplatin. Subjects in both cohorts will be treated until disease progression, toxicity is intolerable, informed consent is withdrawn, and investigators determine that medication must be discontinued. Drug efficacy and safety data will be collected.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Breast Cancer

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Non-Randomized
    Enrollment
    59 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Cohort HR+/HER2+
    Arm Type
    Experimental
    Arm Description
    Hormone receptor negative, HER2 positive participants will receive Pyrotinib in combination with Temozolomide until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
    Arm Title
    Cohort HR-/HER2-
    Arm Type
    Experimental
    Arm Description
    Hormone receptor negative, HER2 negative participants will receive SHR1316 in combination with bevacizumab plus cisplatin or carboplatin until disease progression, unacceptable toxicity, withdrawal of consent or death, whichever occurs first.
    Intervention Type
    Drug
    Intervention Name(s)
    Pyrotinib
    Other Intervention Name(s)
    SHR-1258
    Intervention Description
    PO
    Intervention Type
    Drug
    Intervention Name(s)
    Temozolomide Injection
    Other Intervention Name(s)
    Ainituo
    Intervention Description
    IV
    Intervention Type
    Drug
    Intervention Name(s)
    SHR-1316
    Other Intervention Name(s)
    HTI-1088
    Intervention Description
    IV
    Intervention Type
    Drug
    Intervention Name(s)
    Bevacizumab
    Other Intervention Name(s)
    Avastin
    Intervention Description
    IV
    Intervention Type
    Drug
    Intervention Name(s)
    Cisplatin/Carboplatin
    Other Intervention Name(s)
    Bobei
    Intervention Description
    IV
    Primary Outcome Measure Information:
    Title
    Overall Response Rate in the CNS
    Description
    CNS ORR will be assessed by the investigator according to RANO-BM criteria. According to these criteria Complete Response (CR) will be defined as the disappearance of all CNS target lesions sustained for at least 4 weeks; no new lesions, no corticosteroids; stable or improved clinically. Partial Response (PR) will be defined as a decrease of at least 30% in the sum longest diameter (LD) of CNS target lesions, taking as reference the baseline sum LD, sustained for at least 4 weeks; no new lesions; no corticosteroids; stable or improved clinically.
    Time Frame
    from enrollment to progression or death (for any reason), assessed up to 24 months
    Secondary Outcome Measure Information:
    Title
    Clinical Benefit Rate in the CNS
    Description
    CNS clinical benefit rate (CBR) will be defined as the percentage of patients who experience a CR, PR or Stable Disease (SD) for at least 24 weeks.
    Time Frame
    from enrollment to progression or death (for any reason), assessed up to 24 months
    Title
    Progression-free survival
    Description
    PFS will be defined as the time from the first dose of treatment to death or disease progression.
    Time Frame
    Up to 2 years
    Title
    Overall survival
    Description
    OS will be defined as the time from the first dose of treatment to death for any cause.
    Time Frame
    Up to 2 years
    Title
    First progression site
    Description
    The first lesion to progress.
    Time Frame
    Up to 2 years
    Title
    Safety as assessed by percentage of patients with any Adverse Event
    Description
    Adverse event according to NCI-CTC AE 5.0
    Time Frame
    Up to 2 years

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    80 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Age ≥ 18 years old, and ≤ 70 years old, both genders; ECOG performance status 0-2; Pathological tests confirm HR-negative / HER2-positive or HR-negative / HER2-negative breast cancer;there is evidence of local recurrence or metastasis;not suitable with curative surgery or radiation therapy;HR negative is defined as: ER-negative and PR-negative, the proportion of positively stained tumor cells in all tumor cells is <1%;HER2-positive is defined as: Immunohistochemical detection of HER2 (3+) or fluorescence in situ hybridization (FISH) detection result is positive; Patients with HER2 + breast cancer who have previously received trastuzumab and taxanes; For TNBC, it is required that no platinum drugs have been used before, or platinum drugs have been used (cisplatin/carboplatin only one regimen) and platinum sensitive: no progression during at least 4 cycles of treatment, more than 3 month period between last platinum regimen and the progression of disease; MRI confirmed brain metastases, at least one intracranial parenchymal metastatic lesion with a longest diameter ≥ 1.0 cm without prior radiotherapy; Mannitol or steroid hormone therapy is allowed before enrollment, but the dose of steroid hormone should be stable for at least one week; Adequate function of major organs meets the following requirements: (1)Blood routine ANC≥1.5×109/L; PLT≥75×109/L; Hb≥90 g/L(Allows blood transfusion or the use of medication to ensure that the content of hemoglobin) (2)Coagulation: INR≤1.5,APTT≤1.5×ULN, PT does not exceed the upper limit of normal (3)Blood biochemistry TBIL≤1.5 × ULN; ALT and AST≤3 × ULN (liver metastasis≤5.0 × ULN); Urea nitrogen ≤ 1.5 × ULN; Cr≤1.5 × ULN or creatinine clearance ≥50 mL / min (Cockcroft-Gault formula) (4)Cardiac ultrasound: LVEF≥50%; (5)12-lead ECG: females QTcF interval <470msec and males <450ms; 8.Willing to join the study, sign informed consent, have good compliance and cooperate with follow-up. Exclusion Criteria: Leptomeningeal or cystic metastases confirmed by MRI or lumbar puncture. Presence of third interstitial fluid that cannot be controlled by drainage or other methods (e.g., a large amount of pleural effusion and ascites); Suffering from gastrointestinal diseases such as intestinal obstruction, peptic ulcer or active bleeding, which affects the taking and absorption of drugs; Whole brain radiotherapy, chemotherapy or surgery within 14 days prior to enrollment. Has received prior therapy with trastuzumab within the previous week; Subjects with HR+/HER2- who has received prior therapy with temozolomide. Subjects with HR-/HER2- who has received prior therapy with bevacizumab or PD-1/PD-L1; Any previous or concurrent treatment with Anti-HER2 TKIs; Participation in any other clinical trials within 2 weeks of enrollment; Concurrent use of any other Anti-cancer drugs; Other malignancies within 5 years, except cured in-situ of uterine cervix carcinoma , skin basal cell carcinoma and squamous-cell carcinoma; History of heart disease: (1) Arrhythmias requiring medical treatment or clinical significance, (2) Myocardial infarction, (3) Heart failure, (4)Any heart diseases that investigator believes not suitable for this study; History of allergy or hypersensitivity to any of the study drugs or study drug components; History of immunodeficiency including HIV-positive, active hepatitis B/C, other acquired, congenital immunodeficiency disease or history of organ transplantation; A clear history of neurological or mental disorders, including epilepsy or dementia; Pregnant or breastfeeding women. Women of childbearing potential who have a positive pregnancy test or unwilling to use adequate contraception prior to enrollment and for the duration of study participation; According to the investigator's judgment, there is a concomitant disease that seriously endangers the safety of subjects or affects the completion of the study (including but not limited to severe hypertension, severe diabetes, active infection, thyroid disease that cannot be controlled by drugs); Any condition which in the investigator's opinion makes the subjects unsuitable for the study participation.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Zhang Jian
    Phone
    13918273761
    Email
    syner2000@163.com
    First Name & Middle Initial & Last Name or Official Title & Degree
    Li Ting
    Phone
    13917792964
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Jian Zhang,MD
    Organizational Affiliation
    Fudan University
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Learn more about this trial

    A Multi-cohort Phase II Study of HER2-positive and Triple-negative Breast Cancer Brain Metastases.

    We'll reach out to this number within 24 hrs