Shorter Chemo-Immunotherapy Without Anthracycline Drugs for Early-Stage Triple Negative Breast Cancer

Résumé

This phase III trial compares the effects of shorter chemotherapy (chemo)-immunotherapy without anthracyclines to usual chemo-immunotherapy for the treatment of early-stage triple negative breast cancer. Paclitaxel is in a class of medications called anti-microtubule agents. It stops cancer cells from growing and dividing and may kill them. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of cancer cells. Cyclophosphamide is in a class of medications called alkylating agents. It works by damaging the cell's deoxyribonucleic acid (DNA) and may kill cancer cells. It may also lower the body's immune response. Docetaxel is in a class of medications called taxanes. It stops cancer cells from growing and dividing and may kill them. Doxorubicin is an anthracycline chemotherapy drug that damages DNA and may kill cancer cells. Pembrolizumab may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Shorter treatment without anthracycline chemotherapy may work the same as the usual anthracycline chemotherapy treatment for early-stage triple negative breast cancer.

Éligibilité

Conception de l'étude

Critères de jugement

1. Critère de jugement principal

   Breast cancer event-free survival (BC-EFS)

   Time from randomization to the earliest occurrence of any of the following events: progression prior to surgery, invasive recurrence after surgery, new contralateral breast cancer, or death due to any cause. New non-breast primaries are not included as events. BC-EFS will be compared between the treatment arms using Cox regression with adjustment for nodal status and sTIL enrichment.

   Délai Up to 5 years

2. Critère de jugement secondaire

   Pathologic complete response (pCR)

   pCR rates by assigned treatment arm will be compared using a difference of two proportions overall and by stromal tumor infiltrating lymphocytes (sTIL) group. Additionally, a multivariable logistic regression model will estimate the odds ratio for treatment adjusting for nodal status and sTIL group.

   Délai From date of randomization to date of the earliest occurrence of any of the following events: progression prior to surgery, invasive recurrence after surgery, new contralateral breast cancer, or death due to any cause, assessed up to 5 years

3. Critère de jugement secondaire

   Residual cancer burden (RCB)

   RCB 0/I rates (i.e., RCB-0 and RCB-I combined) by assigned treatment arm will be compared using a difference of two proportions overall and by sTIL group. Additionally, a multivariable logistic regression model will estimate the odds ratio for treatment adjusting for nodal status and sTIL group.

   Délai Up to 5 years

4. Critère de jugement secondaire

   Distant relapse-free survival (DRFS)

   DRFS will be compared by treatment arms using Cox regression for treatment adjusted by nodal status and sTIL status.

   Délai From date of randomization to date of invasive distant disease recurrence or death due to any cause, assessed up to 5 years

5. Critère de jugement secondaire

   Overall survival (OS)

   OS will be compared by treatment arms using Cox regression for treatment adjusted by nodal status and sTIL status.

   Délai From date of randomization to date of death due to any cause, assessed up to 5 years

6. Critère de jugement secondaire

   Distant relapse-free interval (DRFI)

   DRFI will be compared by treatment arms using Cox regression for treatment adjusted by nodal status and sTIL status. Deaths not due to breast cancer will be considered competing risks in this analysis. Cumulative incidence curves will describe the two arms over the follow-up period from randomization.

   Délai From date of randomization to date of invasive distant disease recurrence or death due to breast cancer or its treatment, assessed up to 5 years

7. Critère de jugement secondaire

   Relapse free survival (RFS)

   RFS measured from time of surgery will compare treatment arms in a Cox regression for patients who had pCR. Nodal status and sTIL status will be included as covariates if there are sufficient numbers of events for the analysis. The expectation is that invasive breast cancer-free survival after pCR should not differ by treatment assignment.

   Délai From time of surgery to date of invasive distant disease recurrence or death due to breast cancer or its treatment, assessed up to 5 years

8. Critère de jugement secondaire

   RFS

   RFS measured from time of surgery will compare treatment arms in a Cox regression for patients who did not have a pCR. Nodal status and sTIL status will be included as covariates.

   Délai From time of surgery to date of invasive distant disease recurrence or death due to breast cancer or its treatment, assessed up to 5 years

9. Critère de jugement secondaire

   Incidence of adverse events

   Rates of adverse events will be compared between treatment arms for those initiating the assigned therapy.

   Délai Up to 5 years

10. Critère de jugement secondaire

    Patient-Reported Fatigue

    Participant-reported fatigue will be compared between treatment arms using the Participant-Reported Outcomes Measurement Information System (PROMIS) Short Form v1.0 - Fatigue 7a at 3 weeks after the last neoadjuvant systemic therapy dose and at 18 months after randomization. The PROMIS Fatigue-7a is a validated 7-item questionnaire that assesses participant-reported fatigue in the past 7 days. Raw scores are converted to T-scores with a mean of 50 and a standard deviation of 10. Higher T-scores indicate more fatigue.

    Délai Up to 18 months

11. Critère de jugement secondaire

    Patient-Reported Physical Function

    Participant-reported physical function will be compared between treatment arms using the PROMIS-29 Profile v2.1 physical function subscale score at 3-5 weeks after the last neoadjuvant systemic therapy dose. The PROMIS-29 Profile is a validated 29-item questionnaire that assesses participant-reported symptoms in 9 domains. Raw scores for each subscale are converted to T-scores with a mean of 50 and a standard deviation of 10. This outcome will be assessed using the 4-item physical functioning subscale. Higher T-scores indicate greater physical function.

    Délai Up to 5 weeks after the last neoadjuvant systemic therapy dose

12. Critère de jugement secondaire

    Patient-Reported Physical Function

    Participant-reported physical function will be compared between treatment arms using the PROMIS-29 Profile v2.1 physical function subscale score at 18 months after randomization. The PROMIS-29 Profile is a validated 29-item questionnaire that assesses participant-reported symptoms in 9 domains. Raw scores for each subscale are converted to T-scores with a mean of 50 and a standard deviation of 10. This outcome will be assessed using the 4-item physical functioning subscale. Higher T-scores indicate greater physical function.

    Délai Up to 18 months

Dates

Réelle signifie que l'événement a eu lieu. Estimée signifie que le promoteur s'y attend. Les deux ont un sens différent.

Lieux

923 sites sont en recrutement

913 sites supplémentaires sont indiqués dans la fiche du registre.

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