- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02194049
Cisplatin, Etoposide and PI3K Inhibitor BKM120 in Treating Patients With Advanced Solid Tumors or Small Cell Lung Cancer
Phase I Trial of Cisplatin and Etoposide Plus BKM120 in Advanced Solid Tumors, With an Emphasis on Small Cell Lung Cancer
Study Overview
Status
Intervention / Treatment
Detailed Description
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.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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California
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Sacramento, California, United States, 95817
- University of California at Davis Cancer Center
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Histological or cytological proven advanced solid tumors
- =< 3 chemotherapy regimens for metastatic disease; any number of prior targeted or biologic therapies is allowed; (in the expansion cohort, patients must be chemo naïve)
- ECOG performance status =< 2
- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
- Platelets >= 100 x 10^9/L
- Hemoglobin (Hb) > 9 g/dL
- Total calcium (corrected for serum albumin) within normal limits (bisphosphonate use for malignant hypercalcemia control is not allowed)
- Magnesium >= the lower limit of normal
- Potassium within normal limits for the institution
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal range (or =< 3.0 x upper limit of normal (ULN) if liver metastases are present)
- Serum bilirubin within normal range (or =< 1.5 x ULN if liver metastases are present; or total bilirubin =< 3.0 x ULN with direct bilirubin within normal range in patients with well documented Gilbert Syndrome)
- Serum creatinine =< 1.5 x ULN or calculated clearance >= 60 mL/min
- Serum albumin >= 3 g/dl
- Serum amylase =< ULN
- Serum lipase =< ULN
- Fasting plasma glucose =< 120 mg/dL (6.7 mmol/L)
- International normalized ratio (INR) =< 2
- Ability to swallow pills
- Negative serum pregnancy test
Exclusion Criteria:
- Received prior treatment with a P13K inhibitor
- Received > 300 mg/m^2 of cisplatin and/or for whom cisplatin would not be beneficial
- Prior treatment with any investigational drug within the preceding 3 weeks
- Known hypersensitivity to BKM120 or to its excipients
- Untreated brain metastases are excluded
- Acute or chronic liver, renal disease or pancreatitis
- Following mood disorders as judged by the Investigator or a psychiatrist, or as a result of patient's mood assessment questionnaire
- Diarrhea >= CTCAE grade 2
- Active cardiac disease
- History of cardiac dysfunction
- Poorly controlled diabetes mellitus or steroid-induced diabetes mellitus
- Other concurrent severe and/or uncontrolled concomitant medical conditions
- 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
- Treated with any hematopoietic colony-stimulating growth factors
- Currently receiving treatment with medication with a known risk to prolong the QT interval or inducing torsades de pointes and the treatment cannot either be discontinued or switched to a different medication prior to starting study drug
- Chronic treatment with steroids or another immunosuppressive agent
- Herbal medications and certain fruits within 7 days prior to starting study drug
- 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
- Intravenous chemotherapy or targeted anticancer therapy =< 4 weeks
- Any continuous or intermittent oral small molecule therapeutics
- Received wide field radiotherapy =< 4 weeks or limited field radiation for palliation =< 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy
- Undergone major surgery =< 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy
- Currently taking therapeutic doses of warfarin sodium or any other Coumadin-derivative anticoagulant
- Women who are pregnant or breast feeding or adults of reproductive potential not employing an effective method of birth control
- Known diagnosis of HIV infection
- History of another active malignancy
- Unable or unwilling to abide by the study protocol or cooperate fully with the investigator treatments
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: BKM 120, cisplatin, etoposide
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.
|
Given IV
Other Names:
Given IV
Other Names:
Given PO
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
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
Time Frame: Up to 28 days post-treatment
|
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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Up to 28 days post-treatment
|
Secondary Outcome Measures
Outcome Measure |
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
Time Frame: 21 days
|
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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21 days
|
Response rate assessed by computed tomography (CT) scan based on Response Evaluation Criteria In Solid Tumors (RECIST)
Time Frame: Up to 30 days
|
Response rate among patients with measurable disease will be summarized by exact binomial confidence intervals
|
Up to 30 days
|
Overall survival
Time Frame: Up to 30 days
|
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.
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Up to 30 days
|
Time to progression (TTP) based on RECIST
Time Frame: Up to 30 days
|
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.
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Up to 30 days
|
Pharmacokinetic analysis
Time Frame: 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
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Pharmacokinetic analysis will use non-linear curve fitting methods to estimate the mean peak concentration.
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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
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Collaborators and Investigators
Sponsor
Collaborators
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Respiratory Tract Diseases
- Neoplasms
- Lung Diseases
- Neoplasms by Site
- Respiratory Tract Neoplasms
- Thoracic Neoplasms
- Carcinoma, Bronchogenic
- Bronchial Neoplasms
- Lung Neoplasms
- Small Cell Lung Carcinoma
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Antineoplastic Agents, Phytogenic
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Etoposide
- Etoposide phosphate
Other Study ID Numbers
- UCDCC#239 (Other Identifier: University of California at Davis Cancer Center)
- 470970 (Registry Identifier: UC Davis)
- CBKM120ZUS38T (Other Identifier: Novartis)
- NCI-2014-00218 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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