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

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

  • ORG STUDY ID: 10-192
  • NCT ID: NCT01297452

Conditions

  • Solid Tumors

Interventions

DrugSynonymsArms
BKM120 days 1 - 21 plus paclitaxel + carboplatinBKM120 (days 1 - 21) + paclitaxel + carboplatin
BKM120 (days 1 - 28, ) plus paclitaxel + carboplatinBKM120 (days 1 - 21) + paclitaxel + carboplatin exp B
BKM120 (days 1-21) + paclitaxel (day 1) + carboplatin (day 1)BKM120 (days 1-21) + paclitaxel (day 1) + carboplatin (day 1)
BKM120, Paclitaxel + CarboplatinBKM120 (days 1 - 21) + paclitaxel + carboplatin

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.

Trial Arms

NameTypeDescriptionInterventions
BKM120 (days 1 - 21) + paclitaxel + carboplatinExperimentalThis 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, Paclitaxel + Carboplatin
BKM120 (days 1 - 28, ) + paclitaxel + carboplatinExperimentalThis 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)ExperimentalEXPANSION 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 exp BExperimentalExpansion 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 (days 1 - 28, ) plus 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:To establish the phase II recommended dose of daily oral BKM120
Time Frame:2 years
Safety Issue:
Description:for patients with advanced solid tumors, BKM120 in combination with two different schedules of paclitaxel and carboplatin.

Secondary Outcome Measures

Measure:To describe the safety of BKM120 combined with paclitaxel and carboplatin,
Time Frame:weekly clinic visits during Cycle 1, on Day 1 of subsequent cycles,
Safety Issue:
Description:Patients will be evaluated by MD at weekly clinic visits during Cycle 1, on Day 1 of subsequent cycles, and will have additional evaluations if clinically indicated. Toxicities will be assessed according to NCI common toxicity criteria (CTC) version 4.0
Measure:To determine the pharmacokinetic profile of daily BKM120.
Time Frame:2 years
Safety Issue:
Description:when given in combination with carboplatin and paclitaxel. The area under the curve (AUC0→∞), half-life (t½), and maximum concentration (Cmax) for BKM120 will be determined by noncompartmental analysis.(except for Expansion Cohort B)
Measure:To describe and tabulate the radiographic response rate of BKM120 in combination with carboplatin and paclitaxel,
Time Frame:2 years
Safety Issue:
Description:there is insufficient sample size to support a formal analysis of response rate. As such, radiographic response data will be tabulated and presented in descriptive form.
Measure:Correlative Tissue Studies
Time Frame:2 years
Safety Issue:
Description:we will calculate the proportion of cases with positive staining of PTEN along with a 95% confidence interval, using the Clopper and Pearson method for exact small sample inference. For Sequenom Analysis, we will calculate the proportion of cases that are positive for each mutation

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • BKM120
  • CARBOPLATIN
  • TAXOL (PACLITAXEL)
  • Chemotherapy
  • 10-192

Last Updated

March 31, 2017