Clinical Trials /

Comparison of Single-Agent Carboplatin vs the Combination of Carboplatin and Everolimus for the Treatment of Advanced Triple-Negative Breast Cancer

NCT02531932

Description:

The purpose of this study is to evaluate the safety and effectiveness of carboplatin compared to the combination of carboplatin and everolimus for the treatment of advanced triple-negative breast cancer (TNBC).

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Comparison of Single-Agent <span class="go-doc-concept go-doc-intervention">Carboplatin</span> vs the Combination of <span class="go-doc-concept go-doc-intervention">Carboplatin</span> and <span class="go-doc-concept go-doc-intervention">Everolimus</span> for the Treatment of Advanced <span class="go-doc-concept go-doc-keyword">Triple-Negative</span> <span class="go-doc-concept go-doc-disease">Breast Cancer</span>

Title

  • Brief Title: Comparison of Single-Agent Carboplatin vs the Combination of Carboplatin and Everolimus for the Treatment of Advanced Triple-Negative Breast Cancer
  • Official Title: A Multi-Centered Randomized Phase II Study Comparison of Single-Agent Carboplatin vs the Combination of Carboplatin and Everolimus for the Treatment of Advanced Triple-Negative Breast Cancer
  • Clinical Trial IDs

    NCT ID: NCT02531932

    ORG ID: GCO 15-1075

    Trial Conditions

    Breast Cancer

    Trial Interventions

    Drug Synonyms Arms
    Carboplatin Paraplatin Carboplatin alone, Carboplatin + Everolimus
    Everolimus Certican, Zortress, Votubia Carboplatin + Everolimus

    Trial Purpose

    The purpose of this study is to evaluate the safety and effectiveness of carboplatin
    compared to the combination of carboplatin and everolimus for the treatment of advanced
    triple-negative breast cancer (TNBC).

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    Carboplatin alone Active Comparator AUC 4 every 3 weeks as an IV infusion Carboplatin
    Carboplatin + Everolimus Experimental Carboplatin AUC 4 every 3 weeks IV infusion plus daily oral everolimus 5mg pill Carboplatin, Everolimus

    Eligibility Criteria

    Inclusion Criteria:

    - Women with metastatic breast cancer (measurable or evaluable including bone
    metastases only)

    - Histologically confirmed triple negative breast cancer (ER< 10%, PR < 10%, Her2neu
    IHC 0 or 1 or FISH/ISH negative)

    - Age 18 years

    - WHO performance status 2

    - Adequate bone marrow function as shown by: ANC 1.5 x 10^9/L, Platelets 75 x
    10^9/L, Hb >9 g/dL

    - Adequate liver function as shown by:

    - serum bilirubin 1.5 x ULN

    - ALT and AST 2.5x ULN ( 5x ULN in patients with liver metastases)

    - Adequate renal function: serum creatinine 1.5 x ULN

    - Signed informed consent

    - Patients may have had up to 3 prior regimens for metastatic disease

    - A baseline CT chest/abdomen/pelvis and bone scan or PET/CT

    - Negative serum pregnancy test within 7 days prior to starting treatment

    - Stable brain metastases allowed (> 3 months stable post treatment with
    surgery+/-radiation or radiation alone and off steroids)

    - Prior carboplatin allowed provided greater than 12 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 PI at the time of
    enrollment. For a current table of Substrates, Inhibitors and Inducers please access
    the following website:http://www.fda.gov/Drugs/DevelopmentApprovalProcess/"

    - 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, 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 DLCO that is 50% of
    the normal predicted value and/or 02 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. HBV DNA and HCV RNA 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.
    See Appendix I (Hep Screening Form)

    - A known history of 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)

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Female

    Primary Outcome Measures

    Progress-free survival (PFS)

    Secondary Outcome Measures

    Overall Response Rate (ORR)

    Overall Survival

    Clinical Benefit Rate

    Trial Keywords

    advanced triple negative breast cancer