A Prospective, Phase II Trial Using ctDNA to Initiate Post-operation Boost Therapy After Adjuvant Chemotherapy in TNBC

Study Overview
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Brief Summary
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Circulating tumor DNA (ctDNA) has been demonstrated to be an effective prognostic marker in breast cancer. Various studies have shown that early TNBC breast cancer patients with positive ctDNA have high risk of cancer recurrence and worse prognosis. This study aimed to identify TNBC patients with positive ctDNA and initiate boost therapy in these high risk patients.

Official Title
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A Prospective, Phase II Trial Using ctDNA to Initiate Post-operation Boost Therapy After Adjuvant Chemotherapy in TNBC (Artemis)

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: capecitabine
* Drug: capecitabine + camrelizumab + apatinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient is ≥ 18 years-old at the time of consent to participate this trial Stage II - III primary triple negative breast cancer patients(TNBC), TNBC is defined as ER <=1%, PR <=1%；HER2 receptor IHC=1, or IHC=2 and FISH negative. positive ctDNA after curative surgery and/or adjuvant chemotherapy ECOG 0-2 If indicated, patient agree to receive adjuvant radiotherapy according to the institutional guidelines Patient receives adjuvant chemotherapy according to the NCCN guidelines Patient has available tumor tissue from the surgical specimen for next generation sequencing(NCS) Patient agrees to give blood samples for ctDNA tests every 3 months in 5 years Exclusion Criteria: Patient has previously received any PD1/PDL1 blockage treatment Pregnant or breast-feeding (lactating) women or women who plan to become pregnant or breast-feed during the trial Patient with distant metastases of breast cancer beyond regional lymph nodes (stage IV according to AJCC 8th edition) Patient participates another interventional clinical trial Patient has a concurrent invasive malignancy or a prior invasive malignancy whose treatment was completed within 3 years before randomization Patient with autoimmune disease preventing the use of camrelizumab Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the Investigator's judgment, cause unacceptable safety risks, contraindicate patient participation in the clinical trial or compromise compliance with the protocol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Capecitabine<br>Patients assigned to this group will receive oral capecitabine at a dose of 650 mg/m2 twice a day by mouth for 1 year | Drug: capecitabine<br>* capecitabine is proved to improve 5-year disease-free survival among women with early-stage triple-negative breast cancer who received standard adjuvant treatment(The SYSUCC-001 Randomized Clinical Trial)<br>|
| Experimental: Capecitabine + Apatinib + Camrelizumab<br>Patients assigned to this group will receive oral capecitabine at a dose of 650 mg/m2 twice a day, Camrelizumab 200mg intravenously, once every two weeks (Q2W), oral apatinib, 250mg, PO, qd for 1 year | Drug: capecitabine + camrelizumab + apatinib<br>* Camrelizumab combined with apatinib is a safe and effective combination proved in patients with advanced TNBC in our early study<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Invasive Disease Free Survival(IDFS) | Invasive Disease-Free Survival for capecitabine versus capecitabine + apatinib + camrelizumab in ctDNA-positive stage II-III TNBC patients, using STEEP criteria | 60 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Distant disease-free survival(DDFS) | Distant Disease-Free Survival for capecitabine versus capecitabine + apatinib + camrelizumab in ctDNA-positive stage II-III TNBC patients, using STEEP criteria | 60 months | 
| Overall Survival | Overall Survival for capecitabine versus capecitabine + apatinib + camrelizumab in ctDNA-positive stage II-III TNBC patients, using STEEP criteria | 60 months | 
| Brain metastasis rate | Brain metastasis rate for capecitabine versus capecitabine + apatinib + camrelizumab in ctDNA-positive stage II-III TNBC patients, using STEEP criteria | 60 months | 
| The rate of adverse effects(AEs) | AEs related to apatinib and/or camrelizumab | 60 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage II-III