Clinical trial NCT06533384: PARPi or Capecitabine Combined With PD-1 Inhibitors as Adjuvant Therapy in High-risk TNBC
Official title: PARPi or Capecitabine Combined With PD-1 Inhibitors Was Selected Based on the Germline BRCA1/2 Mutation vs. PD-1 Inhibitors Alone as Adjuvant Therapy in High-risk Non-pCR TNBC
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Triple-negative Breast Cancer
Lead sponsor: Guangdong Provincial People's Hospital
Sponsor class: OTHER
First posted: 2024-08-01
Enrollment: 310
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: In TNBC patients who have completed neoadjuvant immunotherapy and local treatment, a 9-cycle regimen of PD-1 inhibitor adjuvant immunotherapy is currently considered the standard approach. Based on the classification according to their BRCA mutation status, patients with BRCA mutations choose the PD-1 inhibitor + PARPi regimen, while patients without BRCA mutations opt for the PD-1 inhibitor + capecitabine regimen. Compared to monotherapy with PD-1 inhibitors, these combination regimens may offer improved efficacy and acceptable tolerability. This study is designed as a prospective, randomized, controlled, open-label, single-center phase III trial aimed at assessing the efficacy and safety of selecting PARPi or capecitabine in combination with PD-1 inhibitors based on germline BRCA1/2 mutations as adjuvant therapy in high-risk TNBC patients who have achieved non-pCR after completion of neoadjuvant immunotherapy in conjunction with chemotherapy and local treatment.


Eligibility criteria: Inclusion Criteria:

* Pathologically confirmed invasive breast cancer.
* Negative expression of estrogen receptor (ER) and progesterone receptor (PR) according to immunohistochemistry (i.e., tumor cells showing positive staining in less than 1% of all tumor cells).
* Negative human epidermal growth factor receptor 2 (HER2) status as determined by immunohistochemistry: HER2 score of 0/1+ or, if the score is 2+, HER2/CEP17 ratio less than 2.0 or HER2 gene copy number less than 4, as confirmed by in situ hybridization (ISH).
* Clinical tumor staging: T1c, N1-N2 or T2, N0-N2 or T3, N0-N2 or T4a-d, N0-N2.
* The subjects were required to have good organ function, as evidenced by the following tests conducted within 7 days before randomization:

Hematology examination (excluding blood transfusion or use of hematopoietic stimulating agents for correction):

* Hemoglobin (Hb) ≥ 90 g/L.
* Absolute neutrophil count (ANC) ≥ 1.5 × 109/L.
* Absolute lymphocyte count (ALC) ≥ 0.5 × 109/L.
* Platelet count (PLT) ≥ 100 × 109/L.
* White blood cell count (WBC) ≥ 3.0 × 109/L and ≤ 15 × 109/L.

Serum biochemistry examination (excluding recent blood transfusion or albumin administration):

* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 1.5 times the upper limit of normal (ULN).
* Alkaline phosphatase (ALP) ≤ 2.5 ULN.
* Total bilirubin (TBIL) ≤ 1.5 ULN.
* Serum creatinine (Cr) ≤ 1.5 ULN, with creatinine clearance (CrCL) ≥ 50 mL/min (calculated using the Cockcroft-Gault formula).
* Prothrombin time (PT) and activated partial thromboplastin time (APTT) ≤ 1.5 ULN, and international normalized ratio (INR) ≤ 1.5 ULN (if not receiving anticoagulant therapy).

  * Thyroid-stimulating hormone (TSH) within the normal range; if TSH is abnormal, levels of free triiodothyronine (FT3) and free thyroxine (FT4) should be examined. If FT3/FT4 results are not available, T3 and T4 measurements can be considered, and if T3/T4 levels are within the normal range, the subject can be included.
  * Urine analysis: Urinary protein \< 2+; if urinary protein is ≥ 2+, a 24-hour urine protein quantification should demonstrate protein ≤ 1g.
  * Cardiac echocardiography: Left ventricular ejection fraction (LVEF) ≥ 55%.
  * 12-lead electrocardiogram: Fridericia-corrected QT interval (QTcF) \< 470 msec.
  * Women of childbearing potential must have a negative serum pregnancy test within 3 days prior to initiating medication, and they and their partners must agree to use highly effective methods of contraception during the study and for 180 days after the last administration of the investigational drug.
  * Voluntary participation in the clinical trial and signing of the informed consent form are required.

Exclusion Criteria:

* Known history of allergy to the components of the investigational drug.
* Previous receipt of antitumor treatment or radiation therapy for any malignancy (excluding previously cured cervical carcinoma in situ and basal cell carcinoma).
* Undergone major surgery unrelated to breast cancer within the past 4 weeks, or patients who have not fully recovered from such surgery.
* Inability to swallow, intestinal obstruction, or other factors that may affect the administration and absorption of the medication.
* Severe cardiac disease or discomfort that prevents treatment.
* Presence of mental illness or substance abuse that interferes with compliance.
* Pregnant or breastfeeding women.
* Concurrent participation in other clinical trials.
* Subjects deemed by the investigator to have conditions that pose a serious risk to the safety of the participant or may affect the completion of the study, or individuals who are considered unsuitable for inclusion based on other reasons.

Primary outcomes:
measure: IDFS
timeFrame: Up to approximately 5 years
Secondary outcomes:
measure: OS
timeFrame: Up to approximately 5 years
measure: DDFS
timeFrame: Up to approximately 5 years
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: Up to approximately 5 years
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Department of Breast Cancer, Cancer Center, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University
state: Guangdong
Study officials:
affiliation: Guangdong Provincial People's Hospital
name: Kun Wang, MD
role: STUDY_CHAIR
References: