Clinical Trials /

BKM120 + Carboplatin + Paclitaxel for Patients With Advanced Solid Tumors

NCT01297452

Description:

The purpose of this study is to find out the good and bad effects that occur when BKM120 is added to standard chemotherapy with carboplatin and paclitaxel.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

<span class="go-doc-concept go-doc-intervention">BKM120</span> + <span class="go-doc-concept go-doc-intervention">Carboplatin</span> + <span class="go-doc-concept go-doc-intervention">Paclitaxel</span> for Patients With Advanced Solid Tumors

Title

  • Brief Title: BKM120 + Carboplatin + Paclitaxel for Patients With Advanced Solid Tumors
  • Official Title: A Phase I Study of BKM120 + Carboplatin + Paclitaxel for Patients With Advanced Solid Tumors
  • Clinical Trial IDs

    NCT ID: NCT01297452

    ORG ID: 10-192

    Trial Conditions

    Solid Tumors

    Trial Interventions

    Drug Synonyms Arms
    BKM120 days 1 - 21 plus paclitaxel + carboplatin BKM120 (days 1 - 21) + paclitaxel + carboplatin
    BKM120 (days 1 - 28, ) plus paclitaxel + carboplatin BKM120 (days 1 - 28, ) + paclitaxel + carboplatin
    BKM120 (days 1-21) + paclitaxel (day 1) + carboplatin (day 1) BKM120 (days 1-21) + paclitaxel (day 1) + carboplatin (day 1)
    BKM120, Paclitaxel + Carboplatin BKM120 (days 1 - 21) + paclitaxel + carboplatin

    Trial Purpose

    The purpose of this study is to find out the good and bad effects that occur when BKM120 is
    added to standard chemotherapy with carboplatin and paclitaxel.

    Detailed Description

    Trial Arms

    Name Type Description Interventions
    BKM120 (days 1 - 21) + paclitaxel + carboplatin Experimental This will be a single institution phase I study. The primary objectives are to determine the maximum tolerated dose of BKM120 administered with paclitaxel + carboplatin on both a 21-day cycle with growth factor support (Group 1) BKM120 days 1 - 21 plus paclitaxel + carboplatin
    BKM120 (days 1 - 28, ) + paclitaxel + carboplatin Experimental This will be a single institution phase I study. The primary objectives are to determine the maximum tolerated dose of BKM120 administered + paclitaxel with carboplatin on a 28-day cycle with growth factor support and a 28-day cycle (Group 2). BKM120 (days 1 - 28, ) plus paclitaxel + carboplatin
    BKM120 (days 1-21) + paclitaxel (day 1) + carboplatin (day 1) Experimental EXPANSION COHORT A BKM120 100 mg (days 1 - 21, per dose escalation scheme) plus paclitaxel (200 mg/m2 intravenously, day 1) + carboplatin (AUC 6 intravenously, day 1) on a 21-day cycle. After enrollment to Groups 1 and 2 has been completed and all patients in Group 1 and 2 have completed the DLT monitoring period, up to 6 additional patients will be enrolled in this EXPANSION COHORT A. BKM120 (days 1-21) + paclitaxel (day 1) + carboplatin (day 1)
    BKM120 (days 1 - 21) + paclitaxel + carboplatin Experimental Expansion Cohort B will be restricted to patients with tumors known to harbor PTEN mutation or homozygous deletion. The regimen in Expansion Cohort B will be the same regimen established in Group 1 of the protocol, with BKM120 (now called buparlisib) at 100 mg/day per oral + paclitaxel (175 mg/m2) + carboplatin (AUC 5), both given intravenously (IV) on day 1 of a 21-day cycle BKM120, Paclitaxel + Carboplatin

    Eligibility Criteria

    Inclusion Criteria:

    - Pathologically confirmed recurrent or metastatic advanced solid tumor, for which
    there is no curative-intent treatment option. Pathology confirmation must be
    performed at MSKCC.

    - Age 18 years

    - ECOG performance status 1

    - Life expectancy of 12 weeks

    - Adequate bone marrow function as shown by: ANC 1.5 x 109/L, Platelets 100 x
    109/L, Hemoglobin > 9 g/dL

    - Total calcium (corrected for serum albumin) within normal limits (biphosphonate use
    for malignant hypercalcemia control is not allowed)

    - Magnesium the lower limit of normal

    - Adequate liver function.

    - Serum bilirubin must be within the upper limit of normal. (ULN). AST and ALT and
    Alkaline Phosphatase must be within the range allowing for eligibility. In
    determining eligibility the more abnormal of the two values (AST or ALT) should be
    used.

    - Serum creatinine 1.5 x ULN or 24-hour clearance 55 mL/min

    - Fasting plasma glucose (FPG) 120 mg/dL or 6.7 mmol/L

    - HbA1c 8%

    - Negative serum pregnancy test within 14 days before starting study treatment in women
    with childbearing potential

    - Ability to swallow oral medication

    - EXPANSION COHORT B ONLY: Documented genetic alteration (mutation or homozygous
    deletion) in the PTEN gene, identified by the MSKCC IMPACT assay platform or other
    CLIA-approved test.

    Exclusion Criteria:

    - Patients who have received prior treatment with a P13K inhibitor.

    - Patients with a known hypersensitivity to BKM120 or to its excipients

    - Patients with untreated brain metastases are excluded. However, patients with
    metastatic CNS tumors may participate in this trial, if the patient is > 4 weeks from
    therapy completion (incl. radiation and/or surgery), is clinically stable at the time
    of study entry and is not receiving corticosteroid therapy

    - Patients with acute or chronic liver, renal disease or pancreatitis

    - Patients with the following mood disorders as judged by the Investigator or a
    psychiatrist, or as result of patient's mood assessment questionnaire:

    - medically documented history of or active major depressive episode, bipolar
    disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of
    suicidal attempt or ideation, or homicidal ideation (immediate risk of doing
    harm to others)

    * CTCAE grade 3 anxiety

    - At screening, mood rating scores of 10 on PHQ-9 and/or 15 on GAD-7, unless
    overruled by psychiatrist's assessment

    - Patient selects a response of "1, 2, or 3" for question 9 on PHQ-9 questionnaire
    regarding potential for suicidal thoughts or ideation (independent of the total score
    of the PHQ-9) Note: The psychiatric judgment overrules the mood assessment
    questionnaire result/investigators judgment. If mood rating scores do not meet
    eligibility criteria and/or the investigator deems that a patient has mood disorder
    that renders the patient ineligible, that patient may not be registered to the study
    unless there is a subsequent psychiatric clinic consultation in which the
    psychiatrist overrules the mood assessment questionnaire result/investigator
    judgment.

    - Patients with diarrhea CTCAE grade 2

    - Any of the following concurrent severe and/or uncontrolled medical conditions which
    could compromise participation in the study:

    - ST depression or elevation of 1.5 mm in 2 or more leads

    - Congenital long QT syndrome

    - History or presence of sustained ventricular arrhythmias or atrial fibrillation

    - Clinically significant resting bradycardia (< 50 beats per minutes) QTc > 480 msec on
    screening ECG

    - Complete left bundle branch block

    - Right bundle branch block + left anterior hemiblock (bifascicular block)

    - Unstable angina pectoris 6 months prior to starting study drug

    - Acute myocardial infarction 6 months prior to starting study drug

    - Other clinically significant heart disease such as congestive heart failure requiring
    treatment (NYHA Class III or IV) or uncontrolled hypertension (please refer to
    WHO-ISH guidelines)

    - Patients with uncontrolled diabetes mellitus

    - Other concurrent severe and/or uncontrolled concomitant medical conditions (e.g.,
    active or uncontrolled infection) that could cause unacceptable safety risks or
    compromise compliance with the protocol

    - Impairment of gastrointestinal (GI) function or GI disease that may significantly
    alter the absorption of BKM120 (e.g., ulcerative diseases, uncontrolled nausea,
    vomiting, diarrhea, malabsorption syndrome, or small bowel resection). Patients with
    unresolved diarrhea will be excluded as previously indicated

    - Patients who have been treated with any hematopoietic colony-stimulating growth
    factors (e.g., G-CSF, GM-CSF) 2 weeks prior to starting study drug. Erythropoietin
    or darbepoetin therapy, if initiated at least 2 weeks prior to enrollment, may be
    continued

    - Patients who are currently receiving treatment with QT prolonging medication with a
    known risk to induce Torsades de Pointes and the treatment cannot either be
    discontinued or switched to a different medication prior to starting study drug.
    Please refer to Appendix E for a list of prohibited drugs.

    - Patient is currently being treated with drugs known to be moderate and strong
    inhibitors or inducers of isoenzyme CYP3A, and the treatment cannot be discontinued
    or switched to a different medication prior to starting study drug. Please refer to
    Appendix B for a list of prohibited CYP 3A4 inhibitors and inducers.

    - Patients who have received systemic corticosteroids 2 weeks prior to starting study
    drug. Systemic corticosteroids should not be administered with BKM120 (Usage of
    steroids as premedications and anti-emetics for paclitaxel and carboplatin, per MSKCC
    guidelines, is allowed). Steroids given as part of pre-medications for imaging
    studies are not exclusionary.).

    - Patients who have received chemotherapy or targeted anticancer therapy 4 weeks (6
    weeks for nitrosourea, antibodies or mitomycin-C) prior to starting study drug or who
    have not recovered from side effects of such therapy (except alopecia)

    - Patients who have received any continuous or intermittent small molecule therapeutics
    (excluding monoclonal antibodies) 5 effective half lives prior to starting study
    drug or who have not recovered from side effects of such therapy (except alopecia)

    - Patients who have received radiotherapy within 4 weeks prior to registration

    - Patients who have undergone major surgery 2 weeks prior to starting study drug or
    who have not recovered from side effects of such therapy

    - Patients who are currently taking therapeutic doses of warfarin sodium or any other
    coumadin-derivative anticoagulant.

    - Patient is currently being treated with olanzapine and/or other drugs known to be
    moderate and strong inhibitors or inducers of isoenzyme CYP3A, and the treatment
    cannot be discontinued or switched to a different medication prior to starting study
    drug.

    - Women who are pregnant or breast feeding or adults of reproductive potential not
    employing an effective method of birth control. Double barrier contraceptives must be
    used through the trial by both sexes. Oral, implantable, or injectable contraceptives
    may be affected by cytochrome P450 interactions, and are therefore not considered
    effective for this study.

    - Known diagnosis of human immunodeficiency virus (HIV) infection

    - History of another malignancy within 3 years, except cured basal cell carcinoma of
    the skin or excised carcinoma in situ of the cervix

    - Patient is unable or unwilling to abide by the study protocol or cooperate fully with
    the investigator

    - More than 2 prior cytotoxic chemotherapy regimens for recurrent or metastatic disease

    - Patients with multifocal peripheral sensory alterations or paresthesias (including
    tingling) interfering with function, per patient report (example: activities of daily
    living).

    - Patients receiving other investigational therapies

    - Patients receiving herbal preparations/medications

    - Patients with any prior history of whole pelvic radiation therapy (WPRT)

    - EXPANSION COHORT A ONLY: More than one prior cytotoxic chemotherapy regimen (in the
    setting of recurrent and/or metastatic disease (cytotoxic chemotherapy given as part
    of neo-adjuvant therapy, adjuvant therapy, or concurrent chemoradiation for curative
    intent is not included in this exclusion item). This does not apply to Expansion
    Cohort B.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: N/A

    Eligible Gender: Both

    Primary Outcome Measures

    To establish the phase II recommended dose of daily oral BKM120

    EXPANSION COHORT A:To evaluate the safety and tolerability of daily oral BKM120 (100 mg) + paclitaxel (200 mg/m2) + carboplatin (AUC 6), both given intravenously (IV) on day 1 of a 21-day cycle, with pegfilgrastim support

    EXPANSION COHORT B: To obtain a preliminary description of efficacy of the regimen established in Group 1 among patients with tumors harboring PTEN mutation or homozygous deletion.

    Secondary Outcome Measures

    To describe the safety of BKM120 combined with paclitaxel and carboplatin,

    To determine the pharmacokinetic profile of daily BKM120.

    To describe and tabulate the radiographic response rate of BKM120 in combination with carboplatin and paclitaxel,

    Correlative Tissue Studies

    Trial Keywords

    BKM120

    CARBOPLATIN

    TAXOL (PACLITAXEL)

    Chemotherapy

    10-192