Clinical trial NCT06817525: Nab-P+Cb+PD1 Inhibitors Combined/not Combined with Bevacizumab As Neoadjuvant Therapy for Early TNBC
Official title: Nab-P+Cb+PD1 Inhibitor Combined/not Combined with Bevacizumab Neoadjuvant Therapy for Early TNBC: a Single Center, Non Blinded, Randomized Phase II Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Triple-negative Breast Cancer
Keywords: Pathological complete remission rate
Triple-negative breast cancer
Camrelizumab
Neoadjuvant therapy
Bevacizumab
Lead sponsor: Henan Cancer Hospital
Sponsor class: OTHER_GOV
First posted: 2025-02-10
Enrollment: 64
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: We plan to explore the efficacy and safety of albumin-bound paclitaxel+carboplatin+Camrelizumab combined/not combined with bevacizumab in neoadjuvant therapy for early TNBC patients, optimize the administration method and drug combination therapy.

Detailed description: This study is a single center, non blinded, randomized phase II clinical trial. A total of 64 TNBC patients are planned to be enrolled. Patients who meet the inclusion criteria will be randomly divided into four groups (Group A, Group B,Group C, Group D) at a ratio of 1:1:1:1, and stratified according to T stage and N stage. The administration regimen is as follows: Group A： albumin-bound paclitaxe (260 mg/m²,d 1)+Carboplatin (AUC=5, d 1)+Camrelizumab (200 mg, d 1), 21 days as one cycle, 6 cycles; Group B: albumin-bound paclitaxe (125 mg/m²,d 1,8,15)+Carboplatin (AUC=5, d 1 )+Camrelizumab (200 mg, d 1), 21 days as one cycle, 6 cycles; Group C： albumin-bound paclitaxe (260 mg/m²,d 1, 6 cycles)+Carboplatin (AUC=5,d 1, 6 cycles)+Camrelizumab (200 mg, , d 1, 6 cycles)+Bevacizumab (15mg/kg, d 1,5 cycles), 21 days as one cycle; Group D: albumin-bound paclitaxe (125 mg/m²,d 1,8,15,6 cycles)+Carboplatin (AUC=5, d 1, 6 cycles)+Camrelizumab (200 mg, d 1, 6 cycles)+Bevacizumab (15mg/kg, d 1,5 cycles), 21 days as one cycle;

Primary endpoint: Pathological complete response rate (pCR rate).

Secondary study endpoints: Objective response rate (ORR), event free survival rate (EFS), disease-free survival (DFS), distant disease free survival (DDFS), and safety.

Exploratory endpoints: Differences in efficacy and immune microenvironment under different administration methods, synergistic effect of bevacizumab and immunotherapy.

Eligibility criteria: Inclusion Criteria:

1. Age: 18-65 years old;
2. Clinically and pathologically confirmed cT2- cT4d, or cT1c with axillary lymph node metastasis;
3. Three negative type and invasive breast cancer confirmed by histopathology;

   Three negative breast cancer is defined as:
   * ER and PR negative (IHC nuclear staining\<10%)
   * Her-2 negative (IHC 0, 1+without FISH, or IHC 2+without FISH amplification)
4. Clinically measurable lesions:

   Measurable lesions displayed by ultrasound, mammography, or MR (optional) within one month prior to screening;
5. Organ and bone marrow function tests within 2 weeks before chemotherapy indicate no contraindications for chemotherapy:

   * Absolute value of neutrophil count ≥ 2.0 × 109/L
   * Hemoglobin ≥ 100g/L
   * Platelet count ≥ 100 × 109/L
   * Total bilirubin\<1.5 ULN (upper limit of normal)
   * Creatinine\<1.5 × ULN
   * AST/ALT \< 1.5×ULN；
   * Urine test: Urine protein\<2+; If urine protein is ≥ 2+, the 24-hour urine protein quantification display must show protein ≤ 1g
   * Thyroid stimulating hormone (TSH) ≤ upper limit of normal (ULN); If there are abnormalities, T3 and T4 levels should be examined. If T3 and T4 levels are normal, they can be selected
   * Prothrombin time (PT) and activated partial thromboplastin time (APTT) ≤ 1.5 ULN, while meeting international standards Normalization ratio (INR) ≤ 1.5 ULN (not receiving anticoagulant therapy);
6. Cardiac ultrasound EF value ≥ 55%;
7. Women of childbearing age who tested negative for serum pregnancy test 14 days before randomization;
8. ECOG score ≤ 1 point;
9. Voluntary signing of informed consent

Exclusion Criteria:

1. There is evidence of metastatic breast cancer (in order to exclude metastatic breast cancer, chest and abdomen CT and bone scanning should be performed at any time point before diagnosis and randomization; PET/CT scanning can be used as an alternative imaging inspection method);
2. Have Received chemotherapy, endocrine therapy, targeted therapy, radiation therapy, etc. for this disease;
3. The patient has a second primary malignant tumor, in addition to: fully treated skin cancer;
4. Received treatment with anti-PD-1, anti-PDL1, anti-PD-L2 drugs, or other immunotherapy;
5. Diagnosed with immunodeficiency or autoimmune diseases;
6. Severe lung or heart disease;
7. Hepatitis B and C are in active phase;
8. History of organ transplantation or bone marrow transplantation;
9. Pregnant or lactating women;
10. Due to serious and uncontrollable medical conditions, researchers believe there are contraindications to chemotherapy;
11. Screening for clinically significant bleeding symptoms or significant bleeding tendencies within the previous month;
12. Urine routine shows that urine protein is ≥ 2+and confirms that 24-hour urine protein quantification is\>1g;
13. Suffering from serious cardiovascular and cerebrovascular diseases, including but not limited to those that meet NYHA criteria (Grade III or higher), or myocardial infarction or cerebrovascular accident (cerebral ischemia, symptomatic cerebral infarction, etc.) that occurred within 3 months before the first administration, or unstable arrhythmia or unstable angina pectoris accompanied by coronary artery disease that occurred within 1 month before the first administration, or congestive heart failure outside of the above criteria, or symptomatic superior vena cava syndrome, etc;
14. Individuals with hypertension who cannot achieve good control with single antihypertensive medication (systolic blood pressure\>140 mmHg, diastolic blood pressure\>90 mmHg); Individuals with a history of unstable angina pectoris; Newly diagnosed with angina pectoris within the first 3 months of screening or experiencing myocardial infarction events within the first 6 months of screening; Arrhythmia (including QTcF: ≥ 450 ms for males and ≥ 470 ms for females) requires long-term use of antiarrhythmic drugs and New York Heart Association classification of ≥ II heart failure;
15. Screening for arteriovenous thrombosis events such as deep vein thrombosis and pulmonary embolism that occurred within the previous 3 months.

Primary outcomes:
measure: Pathological Complete Response rate(pCR)
timeFrame: through study completion, an average of 1 year
Secondary outcomes:
measure: Objective response rate (ORR)
timeFrame: up to 24 weeks
measure: Event-Free Survival (EFS)
timeFrame: 5 years after surgery
measure: Disease free survival (DFS)
timeFrame: 5 years after surgery
measure: Disease free survival (DDFS)
timeFrame: 5 years after surgery
measure: Incidence of treatment-emergent adverse events
timeFrame: After each cycle of chemotherapy (21 days as 1 cycle)]
Other outcomes:
measure: Association of the tumor microenvironment with treatment response
timeFrame: up to 24 weeks
measure: Association of peripheral blood lymphocyte subsets and cytokines with treatment response
timeFrame: up to 24 weeks
Locations:
city: Zhengzhou
country: China
facility: Henan cancer hospital
state: Henan
Study officials:
affiliation: Henan Cancer Hospital
name: Zhenzhen Liu
role: PRINCIPAL_INVESTIGATOR
References: