Capecitabine Plus Pembrolizumab in Patients With Triple Negative Breast Cancer After Chemo-immunotherapy and Surgery

Triple Negative Breast Neoplasms Clinical Trial

— CAPPA  

Official title:

A Phase III, Randomized, Open-label Study to Evaluate Capecitabine Plus Pembrolizumab vs Pembrolizumab Alone as Post-operative Therapy for Triple Negative Breast Cancer With Residual Disease After Neoadjuvant Chemo-immunotherapy

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05973864
• Other study ID #: UC-BCG-2211
• Secondary ID: 2023-505291-30-0
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: September 2024
• Est. completion date: January 2029

Study information

• Verified date: May 2024
• Source: UNICANCER
• Contact: Telma ROQUE, PhD
• Phone: +33 (0) 1 80 50 12 92
• Email: cappa[@]unicancer.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this clinical trial is to evaluate the efficacity and safety of pembrolizumab and capecitabine compare to pembrolizumab alone, on the invasive disease-free survival, in participants who have triple negative breast cancer (TNBC) with residual disease after neoadjuvant chemotherapy associated with pembrolizumab.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 418
• Est. completion date: January 2029
• Est. primary completion date: January 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Patient must have signed a written informed consent prior to any trial specific procedures. When the patient is physically unable to give their written consent, a trusted person of their choice, independent from the investigator or the sponsor, can confirm in writing the patient's consent;

2. Subject = 18 years of age on day of signing informed consent form;

3. Histologically proven TNBC defined as follows:

1. Human epidermal growth factor receptor 2 (HER2) negativity (American Society of Clinical Oncology and the College of American Pathologists (ASCO/CAP) criteria),

2. AND less than 10% of cells stained by immunohistochemistry for estrogen receptor and Progesterone receptor;

4. TNBC patients previously treated by standard neoadjuvant chemotherapy with a minimum of 6 cycles of immunochemotherapy containing pembrolizumab, per standard of care (and pembrolizumab label) and anthracyclines and/or taxanes (with/without carboplatin). Other drugs may be acceptable following discussion with the sponsor (with the exclusion of capecitabine);

5. Complete resection of the breast tumor(s) (and of any invaded lymph node);

6. No complete pathological response, defined as residual cancer burden (RCB) Class I, II, or III (per local assessment); Note: the final recruited population will contain no more than 25% of patients with RCB I response.

7. Available representative formalin-fixed paraffin-embedded tumor block from surgery specimen with its histological report;

8. Eastern Cooperative Oncology Group (ECOG) Performance Status =2;

9. Adequate organ and bone marrow function. All screening lab tests should be performed within 28 days before randomization;

10. Resolution to at least grade 1 of all acute toxicities from previous therapies including immune related toxicity due to pembrolizumab, except alopecia, immune-related endocrinopathies receiving hormone replacement, and = grade 2 of neuropathy toxicity which are allowed;

11. Minimal/maximal period for prior treatments (i.e. minimal delay from last dose of prior treatment to cycle 1 dose 1 (C1D1)): breast surgery (the wound must have healed prior to C1D1) =2 weeks (maximum 10 weeks); last pembrolizumab injection =3 weeks;

12. Women of child-bearing potential must have a negative serum pregnancy test within 7 days before C1D1;

13. Women of child-bearing potential and male patients must agree to use 1 effective form of contraception from the time of the negative pregnancy test up to 6 months after the last dose of study drugs;

14. Patient should be able and willing to comply with study visits and procedures as per protocol;

15. Patients must be covered by the French medical insurance.

Exclusion Criteria:

1. Radiological or clinical evidence of metastatic disease documented by imaging or clinical examination performed during screening period;

2. Has received capecitabine or other immune-checkpoint inhibitors (ICI) than pembrolizumab in the neoadjuvant chemotherapy (NAC) regimen;

3. Has a known additional malignancy, excepted skin basal cell carcinoma, squamous cell carcinoma of the skin, or in situ cervical cancer or previously treated malignancy with no evidence of disease for = 2 years;

4. Presents a contraindication to continue pembrolizumab treatment as per respective summary of product characteristics (SmPC) including known hypersensitivity;

5. Previous immune-related adverse event of any grade due to pembrolizumab that led to permanent discontinuation of pembrolizumab;

6. Presents a contraindication to capecitabine treatment as per SmPC;

7. Complete Dihydropyrimidine Dehydrogenase (DPD) deficiency;

8. Require the use of one of the following forbidden treatments during the study

treatment period:

• Any investigational anticancer therapy other than the protocol specified treatment,
• Any concurrent chemotherapy, immunotherapy, biologic for cancer treatment, other than the ones stated in the protocol;

9. Pregnant women or women who are breast-feeding;

10. Patients unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons;

11. Persons deprived of their liberty or under protective custody or guardianship;

12. Participation in another therapeutic trial within the 30 days prior to randomization.

Related Conditions & MeSH terms

• Breast Neoplasms
• Triple Negative Breast Neoplasms

Intervention

Drug:
• Pembrolizumab injection
On Day 1 of each cycle for a total of 9 cycles; intravenous (IV) infusion
• Capecitabine tablets
1250 mg/m² BID, on days 1-14 of each 21-day cycle; 8 cycles Dose reduction at 825 mg/m² BID during radiotherapy if indicated

Radiation:
• Local radiotherapy
Local radiotherapy will be performed as per standard practice if indicated.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
UNICANCER

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Invasive Disease-free survival (iDFS)	Invasive disease free survival (iDFS) defined as time from randomization to the first of the following events: local, regional or distant recurrence, or second primary cancer (including contralateral) or death due to any cause.	Up to 5 years
Secondary	Overall survival (OS)	The overall survival is the length of time from randomization that patients enrolled in the study are still alive.	From randomization to death of any cause, up to 5 years.
Secondary	Distant disease-free survival (DDFS)	Distant disease-free survival (DDFS) is defined as the time from the date of randomization to the date of distant relapse or death due to any cause, whichever occurs first.	Throughout study completion, up to 5 years.
Secondary	Acute and late toxicity during the study	The National Cancer Institute-Common Terminology Criteria for Adverse Events version 5 (NCI-CTCAE v5) is widely accepted in the community of oncology research as the leading rating scale for adverse events. This scale, divided into 5 grades (1 = "mild", 2 = "moderate", 3 = "severe", 4 = "life-threatening", and 5 = "death") determined by the investigator, will make it possible to assess the severity of the disorders.	Throughout study completion, up to 5 years.