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

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. Read our disclaimer for details. Identifier: NCT04303988
Recruitment Status : Unknown
Verified March 2020 by Fudan University.
Recruitment status was:  Not yet recruiting
First Posted : March 11, 2020
Last Update Posted : March 11, 2020
Information provided by (Responsible Party):
Fudan University

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.

Condition or disease Intervention/treatment Phase
Breast Cancer Drug: Pyrotinib Drug: Temozolomide Injection Drug: SHR-1316 Drug: Bevacizumab Drug: Cisplatin/Carboplatin Phase 2

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 Subjects in both cohorts will be treated until disease progression, toxicity is intolerable, informed consent is withdrawn, and investigators determine that medication must be discontinued.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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 59 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Prospective, Single-arm, Single-center, Multi-cohort Phase II Clinical Study of HER2-positive and Triple-negative Breast Cancer Brain Metastases
Estimated Study Start Date : March 30, 2020
Estimated Primary Completion Date : December 30, 2021
Estimated Study Completion Date : January 30, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer

Arm Intervention/treatment
Experimental: Cohort HR+/HER2+
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.
Drug: Pyrotinib
Other Name: SHR-1258

Drug: Temozolomide Injection
Other Name: Ainituo

Experimental: Cohort HR-/HER2-
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.
Drug: SHR-1316
Other Name: HTI-1088

Drug: Bevacizumab
Other Name: Avastin

Drug: Cisplatin/Carboplatin
Other Name: Bobei

Primary Outcome Measures :
  1. Overall Response Rate in the CNS [ Time Frame: from enrollment to progression or death (for any reason), assessed up to 24 months ]
    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 :
  1. Clinical Benefit Rate in the CNS [ Time Frame: from enrollment to progression or death (for any reason), assessed up to 24 months ]
    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.

  2. Progression-free survival [ Time Frame: Up to 2 years ]
    PFS will be defined as the time from the first dose of treatment to death or disease progression.

  3. Overall survival [ Time Frame: Up to 2 years ]
    OS will be defined as the time from the first dose of treatment to death for any cause.

  4. First progression site [ Time Frame: Up to 2 years ]
    The first lesion to progress.

  5. Safety as assessed by percentage of patients with any Adverse Event [ Time Frame: Up to 2 years ]
    Adverse event according to NCI-CTC AE 5.0

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

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 identifier (NCT number): NCT04303988

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Contact: Zhang Jian 13918273761
Contact: Li Ting 13917792964

Sponsors and Collaborators
Fudan University
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Study Director: Jian Zhang,MD Fudan University
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Responsible Party: Fudan University Identifier: NCT04303988    
Other Study ID Numbers: HR-BLTN 015
First Posted: March 11, 2020    Key Record Dates
Last Update Posted: March 11, 2020
Last Verified: March 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Breast Neoplasms
Brain Neoplasms
Triple Negative Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Central Nervous System Neoplasms
Nervous System Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action