Breast Cancer Stage II, Breast Cancer Stage III, Early Stage Triple-Negative Breast Carcinoma, Triple -Negative Breast Cancer, Triple Negative Breast Cancer (TNBC), Early Setting
Conditions
Keywords
Immunotherapy, Pembrolizumab, Triple negative breast cancer, Breast cancer, TNBC, Adjuvant
Brief summary
The phase III, multicenter, pragmatic PLANET trial aims to evaluate the benefit and safety of pembrolizumab as an addition to standard of care adjuvant treatment (capecitabine or olaparib) in triple negative breast cancer (TNBC) patients with residual disease (non-pCR) after neoadjuvant chemotherapy and pembrolizumab. All study procedures resemble routine clinical practice as much as possible (i.e., pragmatic clinical trial). In addition to the randomized trial, a registry will be set up, in which patients who reach pCR (and therefore, do not receive adjuvant treatment) will be registered and followed.
Interventions
DRUGStandard of care plus pembrolizumab
Standard of care adjuvant treatment (capecitabine or olaparib) plus pembrolizumab
DRUGStandard of care (capecitabine or olaparib)
Standard of care adjuvant treatment (capecitabine or olaparib)
Sponsors
The Netherlands Cancer Institute
BOOG Study Center
Stichting Treatmeds
Zorgevaluatie en Gepast Gebruik (ZE&GG)
Integraal Kankercentrum Nederland (IKNL)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female, ≥18 years of age on day of signing informed consent 2. Stage II or III TNBC prior to the start of neoadjuvant treatment 1. Locally assessed stage II or III TNBC according to the primary tumor (T) and regional lymph node (N) staging as per the American Joint Committee on Cancer (AJCC) for breast cancer staging criteria version 8 2. Locally assessed estrogen receptor (ER) and/or progesterone receptor (PR) expression \<10% and HER2-negative according to the ASCO-CAP guideline1 3. The patient has received neoadjuvant treatment with chemotherapy (containing at least anthracyclines and taxanes) and pembrolizumab, with a minimum of two 6-weekly (or four 3-weekly) cycles of pembrolizumab 4. The patient underwent breast surgery ≤12 weeks prior to inclusion in the study 5. The patient is scheduled to start standard of care adjuvant treatment with capecitabine or olaparib (pending reimbursement), based on non-pCR after neoadjuvant treatment, defined as RCB score \>02 6. World Health Organization (WHO) performance status 0-2 7. Adequate organ function, as assessed ≤30 days prior to the screening: 1. Absolute neutrophil count (ANC) ≥1,000/mm3 (1.0 x 10e9 /L) 2. Platelets ≥50,000/mm3 (50 x 10e9 /L); 3. Estimated creatinine clearance ≥ 30 mL/min as calculated using the method standard for the institution; 4. Total serum bilirubin ≤1.5 x upper limit of normal (ULN) (≤3.0 x ULN if Gilbert's disease); 5. Aspartate aminotransferase (AST) and alanine transaminase (ALT) ≤3 x ULN 8. Participants of childbearing potential must be willing to use an adequate method of contraception for the course of the study through 6 months after the last dose of study medication 9. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures 10. Willingness to provide written informed consent, according to the Good Clinical Practice (GCP) and national/local regulations
Exclusion criteria
1. Contra-indications for any of the study drugs 2. Other invasive malignancies, except when treated with curative intent without chemotherapy AND more than 5 years ago 3. The presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule 4. Any other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Invasive disease free survival (IDFS) | Up to 10 years after inclusion of the last patient | IDFS, defined as time since randomisation to local or distant breast cancer recurrence, second primary non-breast cancer or death due to any cause, whichever occurs first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Distant disease free survival (DDFS) | Up to 10 years after inclusion of the last patient | DDFS, defined as time from randomisation to distant recurrence or death due to any cause. |
| Overall survival (OS) | Up to 10 years after inclusion of the last patient | OS, defined as time from randomisation to death due to any cause. |
| Safety/adverse events of adjuvant pembrolizumab | Up to 28 days after inclusion of the last patient | Measured by adverse events (AEs), adverse events of special interest (AESIs) and serious adverse events (SAEs). |
| Health related quality of life (HRQoL) - EORTC Quality of Life Questionnaire (QLQ)-C30 | Up to 1 year after inclusion of the last patient | The effect of adjuvant pembrolizumab on health-related quality of life (HRQoL), assessed via Quality of Life Questionnaire (QLQ)-C30. For functional and global HRQoL scales, higher scores represent a better level of functioning and are converted to a 0 to 100 scale. For symptom-oriented scales, a higher score represents more severe symptoms. |
| Health related quality of life (HRQoL) - EORTC Quality of Life Questionnaire (QLQ)-BR42 | Up to 1 year after inclusion of the last patient | The effect of adjuvant pembrolizumab on health-related quality of life (HRQoL), assessed via Quality of Life Questionnaire (QLQ)-BR42. For functional and global HRQoL scales, higher scores represent a better level of functioning and are converted to a 0 to 100 scale. For symptom-oriented scales, a higher score represents more severe symptoms. |
| Health related quality of life (HRQoL) - EuroQol Health Utilities Index (EQ-5D) | Up to 1 year after inclusion of the last patient | The effect of adjuvant pembrolizumab on health-related quality of life (HRQoL), assessed via EuroQol Health Utilities Index (EQ-5D). Overall scores range from 0 to 1, with low scores representing a higher level of dysfunction and 1 as perfect health |
| Cost-utility measured per incremental cost-effectiveness ratio (ICER) | Up to 28 days after inclusion of the last patient | Cost-utility, based on the incremental cost-effectiveness ratio (ICER). |
| Efficacy of pembrolizumab according to tissue biomarkers | Up to 10 years after inclusion of the last patient | Efficacy of pembrolizumab according to tissue biomarkers (including but not limited to stromal tumor infiltrating lymphocytes (sTILs) and programmed death-ligand 1 (PD-L1 expression)) |
Contacts
CONTACTRobin van den Borg, MD
CONTACTAnnemiek van Ommen-Nijhof, MD, PhD
PRINCIPAL_INVESTIGATORGabe Sonke, MD, PhD
Netherlands Cancer Institute - Antoni van Leeuwenhoek
PRINCIPAL_INVESTIGATORMarleen Kok, MD, PhD
Netherlands Cancer Institute - Antoni van Leeuwenhoek
PRINCIPAL_INVESTIGATORAgnes Jager, MD, PhD
Erasmus MC Cancer Institute
Outcome results
None listed