Phase 2
Completed N=28
Ipatasertib in Combination With Carboplatin, Carboplatin/Paclitaxel, or Capecitabine/Atezolizumab in Treating Patients With Metastatic Triple Negative Breast Cancer
Anatomic Stage IV Breast Cancer AJCC v8 · Metastatic Triple-Negative Breast Carcinoma · Prognostic Stage IV Breast Cancer AJCC v8
Source: ClinicalTrials.gov NCT03853707 ↗
Enrolled (actual)
28
Serious AEs
25.0%
Results posted
Mar 2023
Primary outcomePrimary: Progression-free Survival (PFS) — 4.8; 3.9; 8.2 Months
Summary
This phase I trial studies best dose of ipatasertib and how well it works with carboplatin with or without paclitaxel in treating patients with triple negative breast cancer that has spread to other places in the body (metastatic). Ipatasertib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as carboplatin, paclitaxel, and capecitabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. It is not yet known whether giving ipatasertib in combination with carboplatin, carboplatin/paclitaxel, or capecitabine/atezolizumab will work better in treating patients with triple negative breast cancer.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Progression-free Survival (PFS) |
4.8; 3.9; 8.2 | — |
| SECONDARY Overall Response |
7; 2; 3 | — |
| SECONDARY Clinical Benefit Rate |
20.0; 41.7; 50.0 | — |
| SECONDARY Overall Survival (OS) |
11.2; 17.0; NA | — |
Eligibility Criteria
Inclusion Criteria
- Signed informed consent form
- Ability to comply with the study protocol, in the investigator's judgment
- Histologically or cytologically confirmed triple negative breast cancer defined by estrogen receptor (ER) or progesterone receptor (PR) = = 3 months
- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (1,500/uL) without granulocyte colony-stimulating factor support (obtained within 14 days prior to initiation of study treatment)
- Platelet count >= 100 x 10^9/L (100,000/uL) without transfusion (obtained within 14 days prior to initiation of study treatment)
- Hemoglobin >= 9 mg/dL (9 mg/dL) (patients may be transfused to meet this criterion) (obtained within 14 days prior to initiation of study treatment)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = = 50 mL/min (calculated using the Cockcroft-Gault formula) (obtained within 14 days prior to initiation of study treatment)
- Partial thromboplastin time (PTT) (or activated partial thromboplastin time [aPTT]) and international normalized ratio (INR) = = 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus)
- Examples of contraceptive methods with a failure rate of = grade 3 toxicities from previous treatment, not recovered to = = 12 months prior to initiation of the current study
- Prior exposure to paclitaxel or nab-paclitaxel for treatment of metastatic TNBC not allowed for carboplatin/paclitaxel arm; prior treatment of paclitaxel or nab-paclitaxel as neoadjuvant or adjuvant therapy allowed if last dose of therapy completed >= 12 months prior to initiation of the current study
- Prior exposure to capecitabine for treatment of metastatic TNBC not allowed for Arm C; prior treatment of capecitabine as adjuvant therapy allowed if the last dose of therapy completed >= 12 months prior to initiation of the current study for Arm C
- Prior treatment with immune check point inhibitors for Arm C
- Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
- Prior treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 [IL-2]) within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to initiation of study treatment for Arm C
- Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF-alpha agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment, with the following exceptions for Arm C:
- Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for the study after Medical Monitor confirmation has been obtained
- Patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study
- Active autoimmune disorders requiring steroid dose higher than prednisone 10 mg daily for Arm C
- Active disease or receiving treatment for hepatitis B or C or human immunodeficiency virus (HIV) infection for Arm C
- Receipt of a live, attenuated vaccine within 4 weeks prior to enrollment (start of treatment), during treatment, or within 5 months following the last dose of atezolizumab for Arm C
- Known allergy or hypersensitivity to any component of carboplatin and/or paclitaxel or nab-paclitaxel, or capecitabine (5-FU) formulation (for patients planned for the respective arms)
- Known dihydropyrimidine dehydrogenase (DPD) deficiency in patients selected
Data sourced from ClinicalTrials.gov (NCT03853707). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.