Trial Title:
Neoadjuvant Treatment of gBRCA-Mutated HER2-Negative Breast Cancer With HRS-1167 and Famitinib ± Camrelizumab
NCT ID:
NCT06516289
Condition:
BRCA-Mutated Breast Carcinoma
HER2-negative Breast Cancer
Conditions: Official terms:
Breast Neoplasms
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
HRS-1167
Description:
a highly selective PARP1 inhibitor
Arm group label:
Phase 2: Cohort A (HR+/HER2-, gBRCAm)
Arm group label:
Phase 2: Cohort B (HR-/HER2-, gBRCAm)
Arm group label:
Phase 2: Cohort C (HR+/HER2-, gBRCAm expansion cohort)
Arm group label:
Phase 2: Cohort D (HR-/HER2-, gBRCAm expansion cohort)
Arm group label:
Safety run-in
Intervention type:
Drug
Intervention name:
Famitinib
Description:
a tyrosine kinase inhibitor targeting VEGFR2, PDGFR, and c-kit
Arm group label:
Phase 2: Cohort A (HR+/HER2-, gBRCAm)
Arm group label:
Phase 2: Cohort B (HR-/HER2-, gBRCAm)
Arm group label:
Phase 2: Cohort C (HR+/HER2-, gBRCAm expansion cohort)
Arm group label:
Phase 2: Cohort D (HR-/HER2-, gBRCAm expansion cohort)
Arm group label:
Safety run-in
Intervention type:
Drug
Intervention name:
Camrelizumab
Description:
a humanised anti-programmed death-1 (anti PD-1) antibody
Arm group label:
Phase 2: Cohort C (HR+/HER2-, gBRCAm expansion cohort)
Arm group label:
Phase 2: Cohort D (HR-/HER2-, gBRCAm expansion cohort)
Summary:
This study is a prospective, open-label, multi-center, phase II clinical trial designed
for HER2-negative breast cancer with pathogenic mutations in the germline gene (gBRCA1/2)
that were indicated for neoadjuvant chemotherapy. The characteristics of this study are a
precision treatment scheme without chemotherapy, the scheme of HRS-1167 combined with
famitinib neoadjuvant therapy for patients with gBRCA mutations is explored, and the
efficacy of combined immunotherapy is further explored according to the efficacy of the
combination of the two drugs.
Detailed description:
This study is a prospective, open-label, multi-center, phase II clinical trial designed
for HER2-negative breast cancer with pathogenic mutations in the germline gene (gBRCA1/2)
that were indicated for neoadjuvant chemotherapy. The characteristics of this study are a
precision treatment scheme without chemotherapy, the scheme of HRS-1167 combined with
famitinib neoadjuvant therapy for patients with gBRCA mutations is explored, and the
efficacy of combined immunotherapy is further explored according to the efficacy of the
combination of the two drugs. The study consists of a safety run-in period to explore the
safety of HRS-1167 combined with famitinib, which is used to provide a recommended dose
for the combination of HRS-1167 and famitinib. The latter phase II period is used to
explore the efficacy of HRS-1167 plus famitinib /HRS-1167 plus famitinib plus
camrelizumab as neoadjuvant therapy for gBRCA-mutated HER2-negative breast cancer. The
primary endpoints in safety run-in period: the incidence of dose-limiting toxicity (DLT),
the incidence and severity of adverse events (AE) and serious adverse events (SAE) ; in
phase 2: the rate of pathological complete response (pCR) after surgery for each cohort
as assessed by the investigator. Secondary endpoints included residual cancer burden
(RCB) score, 3-year event-free survival (EFS), objective response rate (ORR), complete
cell cycle arrest (CCCA) rate for HR+/HER2 - breast cancer, safety, and translational
exploration study.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Age 18 to 70 years old, female.
2. Patients with histologically confirmed unilateral primary invasive breast cancer who
meet the criteria of cT0-4, N1-3, M0 or cT≥3, N0, M0 (inflammatory breast cancer not
included).
3. Patients with HER-2 negative disease. HER2-negative disease was defined as follows:
disease whose HER-2 is 1+ or negative by immunohistochemical (IHC), or fluorescence
in situ hybridization (FISH) is negative if IHC is 2+.
4. Patients with pathogenic germline BRCA 1/2 mutation.
5. According to the RECIST 1.1 criteria, there is at least one measurable objective
lesion.
6. Eastern Cooperative Oncology Group (ECOG) performance score 0-1.
7. Appropriate haematological, hepatic and renal function (no blood transfusion or
hematopoietic stimulating factors within 14 days): 1) Absolute number of neutrophils
(ANC) ≥ 1.5 x 10^9/L; 2) Platelets ≥ 100 x 10^9/L; 3) Hemoglobin ≥ 90 g/L ; 4) White
blood cell (WBC) ≥ 3.0×10^9/L and ≤15×10^9/L; 5) Total bilirubin (TBIL) ≤ 1.5 times
the upper limit of normal (ULN); 6) AST (SGOT) and ALT (SGPT) ≤ 2.5 x ULN; 7) serum
creatinine (Cr) ≤1.5×ULN, and creatinine clearance (CrCL) ≥50 mL/min
(Cockcroft-Gault equation); 8) Prothrombin time (PT) and activated partial
thromboplastin time (APTT) ≤1.5 ULN with international normalized ratio (INR) ≤1.5
ULN (not receiving anticoagulation); 9) Serum albumin ≥ 2.5g/dL.
8. Left ventricular ejection fraction (LVEF) ≥ 50%.
9. 12-lead ECG: QT interval corrected by Fridericia method (QTcF) < 470 msec.
10. Urine test: urinary protein < 2+; If urinary protein ≥ 2+, 24-hour urinary protein
quantification must show protein ≤1g.
11. Subject is willing and able to comply with the protocol (including contraceptive
measures) for the duration of the study including undergoing treatment and scheduled
visits and examinations including follow up.
12. With good compliance with the planned treatment, are able to understand the
follow-up procedures of this study and sigh the informed consent form.
Exclusion Criteria:
Patients with any of the following were not enrolled in the study:
1. Cancer-related history and treatment history: 1) Bilateral breast cancer; 2)
Previous history of ductal carcinoma in situ (DCIS) or lobular carcinoma in situ
(LCIS); 3) Previous history of invasive or metastatic breast cancer; 4) Any
malignant tumor was diagnosed within 3 years before signing the informed consent,
excluding cured cervical carcinoma in situ, basal cell carcinoma or squamous cell
carcinoma; 5) Received systemic chemotherapy, systemic targeted therapy and local
radiotherapy within 3 years before signing the informed consent; 6) Previously
treated with VEGFR small molecule tyrosine kinase inhibitors (such as famitinib,
sorafenib, sunitinib, regorafenib, etc.) (except bevacizumab); 7) Prior treatment
with PARP inhibitors for any disease;
2. Stage IV breast cancer according to the AJCC staging system, 8th edition.
3. Inflammatory breast cancer or breast rupture.
4. There are clinical symptoms or diseases of the heart that are not well controlled
5. Hypertension that is not well controlled by antihypertensive medication: systolic
blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 90 mmHg has a history of
hypertensive crisis or hypertensive encephalopathy.
6. NCI-CTCAE v5.0 grade ≥2 bleeding events occurred within 4 weeks before the first
medication, including but not limited to hemoptysis (single episode of hemoptysis
volume ≥ 2mL), vaginal bleeding, gastrointestinal bleeding, etc.
7. Excessive arterial/venous thrombosis events occurred within 6 months before the
first medication, such as cerebrovascular accident (including transient ischemic
attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and
pulmonary embolism, etc. Patients with lower extremity intermuscular venous
thrombosis who were evaluated as not requiring anticoagulant therapy, and those
whose mural thrombus caused by catheterization had disappeared and did not require
drug therapy were considered for enrollment.
8. Inability to swallow tablets normally or abnormal gastrointestinal function, which
may affect drug absorption as judged by the researcher;
9. Receipt of a strong inhibitor of CYP3A4, CYP2D6, P-gp, or BCRP from the date of
first dose <5 times of drug half-lives or 14 days; The interval between receiving
treatment with the above enzyme strong inducers and the first dose < 28 days.
10. Evidence of any disease as judged by the investigator (e.g., severe or uncontrolled
systemic disease, including severe systemic infection, uncontrolled hypertension,
renal transplantation and active bleeding disease, coagulation disorders, platelet
dysfunction, severe chronic gastrointestinal disease, or patients with other serious
medical conditions);
11. Have undergone major surgery other than invasive diagnostic procedures, peripherally
inserted central catheter (PICC) procedures, or pathological biopsy within 28 days
prior to the first dose, or are expected to undergo major surgery during the study
period;
12. Unhealed wounds, ulcers, or fractures;
13. Active hepatitis B (defined as hepatitis B surface antigen [HBsAg] positive and
HBV-DNA ≥500IU/ml);
14. Hepatitis C infection (defined as a positive test for hepatitis C virus antibody
[HCV-Ab] and an HCV-RNA test higher than the lower limit of the assay);
15. Known history of human immunodeficiency virus (HIV) infection;
16. Known history of psychotropic substance abuse, alcohol or drug abuse;
17. Active psychiatric disorders (schizophrenia, major depressive disorder, bipolar
disorder, etc.) and depression being treated with antidepressants were not exclusion
criteria.
18. Patients with known allergy or intolerance to the study drug or its excipents;
19. Patients of reproductive age who are pregnant or lactating, and who refuse to use
appropriate contraception during the course of the trial;
20. Participated in other trial studies within 30 days before the first dose of the
study drug, or not more than 5 half-lives since the last dose of the study drug;
21. Patients judged by the investigator to be ineligible for the study.
Gender:
Female
Minimum age:
18 Years
Maximum age:
70 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Breast cancer institute of Fudan University Cancer Hospital
Address:
City:
Shanghai
Zip:
200032
Country:
China
Start date:
July 2024
Completion date:
June 2027
Lead sponsor:
Agency:
Fudan University
Agency class:
Other
Source:
Fudan University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06516289
