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Carboplatin with or without Everolimus in Treating Patients with Metastatic Triple Negative Breast Cancer

Trial Status: Active

This randomized phase II trial studies carboplatin with or without everolimus in treating patients with triple negative breast cancer that has spread to other places in the body. Drugs used in chemotherapy, such as carboplatin and everolimus, 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.

Inclusion Criteria

  • Metastatic breast cancer (measurable or evaluable including bone metastases only)
  • Histologically confirmed triple negative breast cancer (estrogen receptor [ER] < 10%, progesterone receptor [PR] < 10%, Her2neu immunohistochemistry [IHC] 0 or 1 or fluorescence in situ hybridization [FISH]/in situ hybridization [ISH] negative)
  • World Health Organization (WHO) performance status =< 2
  • Absolute neutrophil count >= 1.5 x 10^9/L
  • Platelets >= 75 x 10^9/L
  • Hemoglobin (Hb) > 9 g/dL
  • Serum bilirubin =< 1.5 x upper limit of normal (ULN)
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN (=< 5 x ULN in patients with liver metastases)
  • Serum creatinine =< 1.5 x ULN
  • Signed informed consent
  • Patients may have had up to 3 prior regimens for metastatic disease
  • A baseline computed tomography (CT) chest/abdomen/pelvis and bone scan or positron emission tomography (PET)/CT
  • Negative serum pregnancy test within 7 days prior to starting treatment
  • Stable brain metastases allowed (> 2 weeks, clinically-stable post treatment with surgery +/- radiation or radiation alone and off steroids)
  • Prior carboplatin allowed provided greater than 12 months (mos) have elapsed since last dose of carboplatin

Exclusion Criteria

  • Patients currently receiving anticancer therapies or who have received anticancer therapies within 2 weeks of the start of study drug (including chemotherapy, radiation therapy, and biologics)
  • Patients, who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia) or patients that may require major surgery during the course of the study
  • Prior treatment with any investigational drug within the preceding 2 weeks
  • Patients receiving chronic, systemic treatment with corticosteroids or another immunosuppressive agent, except corticosteroids with a daily dosage equivalent to prednisone =< 20 mg; however, patients receiving corticosteroids must have been on a stable dosage regimen for a minimum of 4 weeks prior to the first treatment with everolimus; topical or inhaled corticosteroids are allowed
  • Co-administration with strong inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole, ritonavir) or P-glycoprotein (PgP) is prohibited; co-administration with moderate CYP3A4 inhibitors (e.g., erythromycin, fluconazole) or PgP inhibitors may be used with caution and everolimus dosing must be discussed with principle investigator (PI) at the time of enrollment
  • Patients who have received live attenuated vaccines within 1 week of start of everolimus and during the study; patient should also avoid close contact with others who have received live attenuated vaccines; examples of live attenuated vaccines include intranasal influenza, measles, mumps, rubella, oral polio, Bacillus Calmette-Guerin (BCG), yellow fever, varicella and TY21a typhoid vaccines
  • Uncontrolled brain metastases
  • Leptomeningeal metastases
  • Other malignancies within the past 3 years except for adequately treated carcinoma of the cervix or basal or squamous cell carcinomas of the skin
  • Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as: * Symptomatic congestive heart failure of New York heart Association class III or IV * Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease * Severely impaired lung function as defined as spirometry and carbon monoxide diffusing capability test (DLCO) that is 50% of the normal predicted value and/or oxygen (O2) saturation that is 89% or less at rest on room air * Uncontrolled diabetes as defined by fasting serum glucose >1.5 x ULN * Active (acute or chronic) or uncontrolled severe infections * Liver disease such as cirrhosis, chronic active hepatitis or chronic persistent hepatitis * Note: A detailed assessment of hepatitis B/C medical history and risk factors must be done at screening for all patients; hepatitis B virus (HBV) deoxyribonucleic acid (DNA) and hepatitis C virus (HCV) ribonucleic acid (RNA) polymerase chain reaction (PCR) testing are required at screening for all patients with a positive medical history based on risk factors and/or confirmation of prior HBV/HCV infection
  • A known history of human immunodeficiency virus (HIV) seropositivity
  • Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of everolimus (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)
  • Patients with an active, bleeding diathesis
  • Patients who have received prior treatment with an mTOR inhibitor (sirolimus, temsirolimus, everolimus)
  • Patients with a known hypersensitivity to everolimus or other rapamycins (sirolimus, temsirolimus) or to its excipients
  • Patients with a known hypersensitivity to carboplatin
  • History of noncompliance to medical regimens
  • Patients unwilling to or unable to comply with the protocol
  • Ongoing alcohol or drug addiction
  • Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods; if barrier contraceptives are being used, these must be continued throughout the trial by both sexes; hormonal contraceptives are not acceptable as a sole method of contraception; (women of childbearing potential must have a negative urine or serum pregnancy test within 7 days prior to administration of everolimus)

New York

New York
Icahn School of Medicine at Mount Sinai
Status: ACTIVE
Contact: Amy Diane Tiersten
Phone: 212-241-3300
Mount Sinai Chelsea
Status: ACTIVE
Contact: Paula Klein
Phone: 212-604-6021
Mount Sinai Saint Luke's
Status: ACTIVE
Contact: Anupama Goel
Phone: 212-523-6769
Mount Sinai West
Status: ACTIVE
Contact: Anupama Goel


I. To compare median progression-free survival (PFS) in patients treated with carboplatin + everolimus with that of patients treated with carboplatin alone.


I. Overall response rate.

II. Overall survival.

III. Clinical benefit rate (defined as the best overall response rate including complete response [CR] + partial response [PR] + stable disease [SD] >= 6 months).

IV. Toxicity.


I. Identify biomarkers of response to everolimus.

II. Assess the hotspot panel on the primary tumor when tissue is available.

III. Assess the hotspot panel on any pre-existing metastatic biopsies that occurred before being considered for the study.

IV. Recommend a baseline biopsy for patients coming on study as well as a biopsy at the time of disease progression.

V. Study any subsequent non-research metastatic biopsies that may be done after the subject is off the study for the same.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive carboplatin intravenously (IV) every 3 weeks in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive carboplatin IV and everolimus orally (PO) daily every 3 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
Icahn School of Medicine at Mount Sinai

Principal Investigator
Amy Diane Tiersten

  • Primary ID 15-1075
  • Secondary IDs NCI-2017-00676
  • ID NCT02531932