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BKM120 + Carboplatin + Paclitaxel for Patients With Advanced Solid Tumors

Information source: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Solid Tumors

Intervention: BKM120 days 1 - 21 plus paclitaxel + carboplatin (Drug); BKM120 (days 1 - 28, ) plus paclitaxel + carboplatin (Drug); BKM120 (days 1-21) + paclitaxel (day 1) + carboplatin (day 1) (Drug); BKM120, Paclitaxel + Carboplatin (Drug)

Phase: Phase 1

Status: Recruiting

Sponsored by: Memorial Sloan Kettering Cancer Center

Official(s) and/or principal investigator(s):
David Hyman, MD, Principal Investigator, Affiliation: Memorial Sloan Kettering Cancer Center

Overall contact:
David Hyman, MD, Phone: 646-888-4544

Summary

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.

Clinical Details

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

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

Primary outcome:

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:

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

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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.

Locations and Contacts

David Hyman, MD, Phone: 646-888-4544

Memorial Sloan Kettering Cancer Center, New York, New York 10065, United States; Recruiting
David Hyman, MD, Phone: 646-888-4544
Anna Varghese, MD, Phone: 646-888-4308
David Hyman, MD, Principal Investigator
Additional Information

Memorial Sloan Kettering Cancer Center

Starting date: February 2011
Last updated: June 16, 2015

Page last updated: August 23, 2015

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