A Phase I Study of BKM120 + Carboplatin + Paclitaxel for Patients With Advanced Solid Tumors
A Phase I Study of BKM120 + Carboplatin + Paclitaxel for Patients With Advanced Solid Tumors
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.
Inclusion Criteria:
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.