A Phase II Study of Triple-negative Breast Cancer Brain Metastases.

NCT04303988 | Recruiting Phase 2

• 1 other identifier: HR-BLTN 015
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

Study to assess the effectiveness and safety of SHR 1316, bevacizumab combined with cisplatin/carboplatin for treatment of triple-negative breast cancer brain metastases.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (5)

• Clinical Benefit Rate in the CNS

  from enrollment to progression or death (for any reason), assessed up to 24 months

• Progression-free survival

  Up to 2 years

• Overall survival

  Up to 2 years

• First progression site

  Up to 2 years

• Safety as assessed by percentage of patients with any Adverse Event

  Up to 2 years

Study Arms (1)

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.

Drug: SHR-1316; Drug: Bevacizumab; Drug: Cisplatin/Carboplatin

Interventions

SHR-1316 DRUG

IV

Also known as: HTI-1088

Cohort HR-/HER2-

Bevacizumab DRUG

IV

Also known as: Avastin

Cohort HR-/HER2-

Cisplatin/Carboplatin DRUG

IV

Also known as: Bobei

Cohort HR-/HER2-

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years old, and ≤ 70 years old, both genders;
• ECOG performance status 0-2;
• Pathological tests confirm 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- negative is defined as: histologically confirmed to be HER2 IHC (0) or HER2 IHC(1+) or HER2 IHC (2+) and FISH(-);
• 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 months 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.

You may not qualify if:

• 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);
• Whole brain radiotherapy, chemotherapy or surgery within 14 days prior to enrollment. Has received prior therapy with Targeted therapy or Endocrine therapy within the previous week；
• Subjects with HR-/HER2- who has received prior therapy with bevacizumab or PD-1/PD-L1；
• 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.

Sponsors & Collaborators

• Fudan University: lead

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Bevacizumab; Cisplatin; Carboplatin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals

Study Officials

• Jian Zhang, MD

  Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jian Zhang, MD

CONTACT

13918273761; syner2000@163.com

Ting Li, MD

CONTACT

13917792964

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: February 24, 2020
• First Posted: March 11, 2020
• Study Start: March 30, 2020
• Primary Completion: December 30, 2024
• Study Completion: May 30, 2025
• Last Updated: July 18, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)