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| ID | Type | Description | Link |
|---|---|---|---|
| 470970 | Registry Identifier | UC Davis | |
| CBKM120ZUS38T | Other Identifier | Novartis | |
| UCDCC#239 | Other Identifier | University of California at Davis Cancer Center | |
| NCI-2014-00218 | Registry Identifier | CTRP (Clinical Trial Reporting Program) |
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| Name | Class |
|---|---|
| Novartis | INDUSTRY |
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This phase I trial studies the side effects and the best dose of PI3K inhibitor BKM120 when given together with cisplatin and etoposide in treating patients with advanced solid tumors or small cell lung cancer. Drugs used in chemotherapy, such as cisplatin and etoposide, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing , or by stopping them from spreading. PI3K inhibitor BKM120 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving PI3K inhibitor BKM120 with cisplatin and etoposide may kill more tumor cells.
PRIMARY OBJECTIVES:
I. To determine the safety and feasibility of combining BKM120 (PI3K inhibitor BKM120) with cisplatin and etoposide in advanced solid tumors, with emphasis on small cell lung cancer (SCLC).
SECONDARY OBJECTIVE:
I. To determine the MTD (maximally tolerated dose) of BKM120 in combination with cisplatin/etoposide.
II. To describe the dose limiting toxicities (DLT) and toxicity profile associated with BKM120 in combination with cisplatin/etoposide.
III. To determine the preliminary efficacy of BKM120 in combination with cisplatin/etoposide in an expanded cohort of patients with SCLC.
IV. To characterize the pharmacokinetic (PK) parameters of BKM120 in this combination.
V. To collect blood samples for future exploratory biomarker analysis.
OUTLINE: This is a dose-escalation study of PI3K inhibitor BKM120.
Patients receive PI3K Inhibitor BKM120 orally (PO) once daily (QD) on days 1-21, cisplatin intravenously (IV) over 2 hours on day 1 and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
After completion of treatment, patients are followed for 30 days.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| BKM 120, cisplatin, etoposide | Experimental | Patients receive PI3K Inhibitor BKM120 PO QD on days 1-21, cisplatin IV over 2 hours on day 1 and etoposide IV over 1 hour on days 1-3. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| BKM120 | Drug | Given PO |
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| Measure | Description | Time Frame |
|---|---|---|
| Incidence of adverse events of combining daily BKM120 with cisplatin and etoposide as graded by the National Cancer Institute (NC) CTCAE version 4.0 | The toxicities observed at each dose level will be summarized in terms of type (organ affected or laboratory determination such as absolute neutrophil count), severity, time of onset (i.e. course number), duration, and reversibility or outcome. | Up to 28 days post-treatment |
| Measure | Description | Time Frame |
|---|---|---|
| MTD defined as the highest dose tested in which fewer than 33% of patients experience DLT attributed to the study drugs when at least 6 patients were treated at that dose, as graded by NCI CTCAE version 4.0 | The toxicities observed at each dose level will be summarized in terms of type (organ affected or laboratory determination such as absolute neutrophil count), severity, time of onset (i.e. course number), duration, and reversibility or outcome. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Karen Kelly | University of California, Davis | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California at Davis Cancer Center | Sacramento | California | 95817 | United States |
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| cisplatin | Drug | Given IV |
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| etoposide | Drug | Given IV |
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| 21 days |
| Response rate assessed by computed tomography (CT) scan based on Response Evaluation Criteria In Solid Tumors (RECIST) | Response rate among patients with measurable disease will be summarized by exact binomial confidence intervals | Up to 30 days |
| Overall survival | Survival will be summarized with Kaplan-Meier plots to describe the outcome of patients treated on this protocol. Median survival time will be estimated using standard life table methods. | Up to 30 days |
| Time to progression (TTP) based on RECIST | TTP will be summarized with Kaplan-Meier plots to describe the outcome of patients treated on this protocol. Median time to progression will be estimated using standard life table methods. | Up to 30 days |
| Pharmacokinetic analysis | Pharmacokinetic analysis will use non-linear curve fitting methods to estimate the mean peak concentration. | Baseline, at 1, 2, 4, 6, and 24 hours of day 1 of course 1, baseline day 15 of course 1, and at 1 and 2 hours post-dose on day 1 of course 2 |
| ID | Term |
|---|---|
| C571178 | NVP-BKM120 |
| D002945 | Cisplatin |
| D005047 | Etoposide |
| ID | Term |
|---|---|
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017672 | Nitrogen Compounds |
| D017671 | Platinum Compounds |
| D011034 | Podophyllotoxin |
| D013764 | Tetrahydronaphthalenes |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |
| D005960 | Glucosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
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