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A Phase I Study of BKM120 + Carboplatin + Paclitaxel for Patients With Advanced Solid Tumors


Phase 1
18 Years
N/A
Open (Enrolling)
Both
Solid Tumors

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Trial Information

A Phase I Study of BKM120 + Carboplatin + Paclitaxel for Patients With Advanced Solid Tumors


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

- Serum amylase ≤ ULN

- Serum lipase ≤ ULN

- Fasting plasma glucose ≤ 140 mg/dL (7.8 mmol/L)

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

- Ability to swallow oral medication

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 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 ONLY: More than one prior cytotoxic chemotherapy regimen (whether
given as part of initial curative intent therapy, or for recurrent/metastatic
disease)

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To establish the phase II recommended dose of daily oral BKM120

Outcome Description:

for patients with advanced solid tumors, BKM120 in combination with two different schedules of paclitaxel and carboplatin.

Outcome Time Frame:

2 years

Safety Issue:

Yes

Principal Investigator

Matthew Fury, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Memorial Sloan-Kettering Cancer Center

Authority:

United States: Food and Drug Administration

Study ID:

10-192

NCT ID:

NCT01297452

Start Date:

February 2011

Completion Date:

February 2014

Related Keywords:

  • Solid Tumors
  • BKM120
  • CARBOPLATIN
  • TAXOL (PACLITAXEL)
  • Chemotherapy
  • 10-192
  • Neoplasms

Name

Location

Memorial Sloan Kettering Cancer CenterNew York, New York  10021