Extensive Stage Small Cell Lung CancerPhase 1NCT02194049
Cisplatin, Etoposide and PI3K Inhibitor BKM120 in Treating Patients With Advanced Solid Tumors or Small Cell Lung Cancer
A Phase 1 study testing BKM120, cisplatin and etoposide in people with Extensive Stage Small Cell Lung Cancer and Unspecified Adult Solid Tumor, Protocol Specific, run by University of California, Davis at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Extensive Stage Small Cell Lung Cancer, Unspecified Adult Solid Tumor, Protocol Specific
- What is being tested?
- BKM120, cisplatin and etoposide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2014to Jun 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California at Davis Cancer Center
Sacramento, California, 95817
About this study
Official title: Phase I Trial of Cisplatin and Etoposide Plus BKM120 in Advanced Solid Tumors, With an Emphasis on Small Cell Lung Cancer
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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.
- 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.
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BKM120Drug
Also called PI3K_Inhibitor_BKM120
Given PO
cisplatinDrug
Also called CACP, CDDP, CPDD, DDP
Given IV
etoposideDrug
Also called EPEG, VP-16, VP-16-213
Given IV
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: BKM120; Drug: cisplatin; Drug: etoposide |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 28 days post-treatment
Secondary outcomes (5)
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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: Up to 30 days
Pharmacokinetic analysis
Pharmacokinetic analysis will use non-linear curve fitting methods to estimate the mean peak concentration.
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jul 2014 (estimated)
- Study startJul 2014
- Primary completionApr 2016
- Study completionJun 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Extensive Stage Small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by University of California, DavisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Davis
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Sponsor
- Investigators
- Karen Kelly, Principal investigator, University of California, Davis
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02194049
- Sponsor's protocol ID
- UCDCC#239
- Other IDs
- 470970, CBKM120ZUS38T, UCDCC#239, NCI-2014-00218
- Status last verified
- Jun 2016
- First submitted
- 10 Jul 2014
- Last updated
- 9 Jan 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 9 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Trial of Cisplatin and Etoposide Plus BKM120 in Advanced Solid Tumors, With an Emphasis on Small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT02194049
- Acronym / sponsor ID
- UCDCC#239
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3 participants (actual)
- Lead sponsor
- University of California, DavisUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- Jul 2014
- Primary completion
- Apr 2016 (actual)
- Study completion
- Jun 2016 (actual)
- First posted
- 18 Jul 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
PRIMARY OBJECTIVES:
- 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:
- 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.
- 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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| BKM 120, cisplatin, etoposide | Experimental | Drug: BKM120, Drug: cisplatin, Drug: etoposidePatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- 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
Key exclusion criteria (27 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BKM120Also: PI3K_Inhibitor_BKM120Given PO | Drug | BKM 120, cisplatin, etoposide |
| cisplatinAlso: CACP, CDDP, CPDD, DDPGiven IV | Drug | BKM 120, cisplatin, etoposide |
| etoposideAlso: EPEG, VP-16, VP-16-213Given IV | Drug | BKM 120, cisplatin, etoposide |
Primary outcome
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.
5 secondary outcomes
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
Response rate assessed by computed tomography (CT) scan based on Response Evaluation Criteria In Solid Tumors (RECIST)
Time frame: Up to 30 days
Overall survival
Time frame: Up to 30 days
Time to progression (TTP) based on RECIST
Time frame: 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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jan 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Karen Kelly principal investigator
University of California, Davis
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing BKM120, cisplatin and etoposide in people with Extensive Stage Small Cell Lung Cancer and Unspecified Adult Solid Tumor, Protocol Specific, run by University of California, Davis at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jan 2018.