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Study to assess the effectiveness and safety of SHR 1316, bevacizumab combined with cisplatin/carboplatin for treatment of triple-negative breast cancer brain metastases.
This is a prospective, single-arm, single-center, Simon's two-stage design, phase II clinical trial in triple-negative breast cancer brain metastases patients. Subjects will receive bevacizumab,SHR1316 combined with cisplatin/carboplatin,and will be treated until disease progression, toxicity is intolerable, informed consent is withdrawn, or investigators determine that medication must be discontinued. Drug efficacy and safety data will be collected.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort HR-/HER2- | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| SHR-1316 | Drug | IV |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | from enrollment to progression or death (for any reason), assessed up to 24 months |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | from enrollment to progression or death (for any reason), assessed up to 24 months |
| Progression-free survival |
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Inclusion Criteria:
(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:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Jian Zhang, MD | Contact | 13918273761 | syner2000@163.com | |
| Ting Li, MD | Contact | 13917792964 |
| Name | Affiliation | Role |
|---|---|---|
| Jian Zhang, MD | Fudan University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fudan University Shanghai Cancer Center | Recruiting | Shanghai | Shanghai Municipality | 200032 | China |
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| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
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| ID | Term |
|---|---|
| D000068258 | Bevacizumab |
| D002945 | Cisplatin |
| D016190 | Carboplatin |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
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| Bevacizumab |
| Drug |
IV |
|
|
| Cisplatin/Carboplatin | Drug | IV |
|
|
PFS will be defined as the time from the first dose of treatment to death or disease progression. |
| Up to 2 years |
| Overall survival | OS will be defined as the time from the first dose of treatment to death for any cause. | Up to 2 years |
| First progression site | The first lesion to progress. | Up to 2 years |
| Safety as assessed by percentage of patients with any Adverse Event | Adverse event according to NCI-CTC AE 5.0 | Up to 2 years |
| D017437 |
| Skin and Connective Tissue Diseases |
| D007162 |
| Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017672 | Nitrogen Compounds |
| D017671 | Platinum Compounds |
| D056831 | Coordination Complexes |
| D009930 | Organic Chemicals |