PARPi or Capecitabine Combined With PD-1 Inhibitors as Adjuvant Therapy in High-risk TNBC

October 31, 2024 updated by: Guangdong Provincial People's Hospital

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
310

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510080
        • Recruiting
        • Department of Breast Cancer, Cancer Center, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Experimental ARM
In the experimental group, patients with confirmed deleterious mutations based on germline BRCA1/2 status receive a combination of Fuzuloparib and Camrelizumab as adjuvant therapy. Patients without germline BRCA1/2 deleterious mutations receive a combination of capecitabine and Camrelizumab as adjuvant therapy.
Drug: As per the germline BRCA1/2 mutation status, the selection of either Fuzuloparib or capecitabine in combination with Camrelizumab is made for adjuvant therapy.
As per the germline BRCA1/2 mutation status, the selection of either Fuzuloparib or capecitabine in combination with Camrelizumab is made for adjuvant therapy.
Active Comparator: Control ARM
9 cycles of Camrelizumab as adjuvant therapy.
Drug: As per the germline BRCA1/2 mutation status, the selection of either Fuzuloparib or capecitabine in combination with Camrelizumab is made for adjuvant therapy.
As per the germline BRCA1/2 mutation status, the selection of either Fuzuloparib or capecitabine in combination with Camrelizumab is made for adjuvant therapy.
Drug: 9 cycles of Camrelizumab as adjuvant therapy.
9 cycles of Camrelizumab as adjuvant therapy.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
IDFS
Time Frame: Up to approximately 5 years
invasive disease free survival
Up to approximately 5 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
OS
Time Frame: Up to approximately 5 years
Overall survival
Up to approximately 5 years
DDFS
Time Frame: Up to approximately 5 years
Distant Disease Free Survival
Up to approximately 5 years
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time Frame: Up to approximately 5 years
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Up to approximately 5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Guangdong Provincial People's Hospital

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Kun Wang, MD, Guangdong Provincial People's Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 1, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2030

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 6, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 29, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 1, 2024

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 4, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 31, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • KY2023-800

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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