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Solid TumorsPhase 1NCT01470209

A Phase I Study of BKM120 and Everolimus in Advanced Solid Malignancies

A Phase 1 study testing BKM120 and Everolimus in people with Solid Tumors and Lung Cancer, run by Emory University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This study will assess the safety of combining two agents (everolimus and BKM120) for the treatment of advanced cancer arising from solid organ in patients who are no longer benefiting from or unable to withstand standard treatment of these conditions. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Solid Tumors, Lung Cancer
What is being tested?
BKM120 and Everolimus
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
43 participants
Where
1 siteUnited States
Study dates
Jan 2012to May 2017
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

  • Histologic or cytologic confirmation of a solid malignancy with established intolerance or refractoriness to standard therapies
  • Age ≥ 18 years
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
  • Patients must have at least one site of measurable disease (per Response Evaluation Criteria in Solid Tumors [RECIST] 1.1 criteria)
  • Adequate organ function including:
  • Bone marrow function as shown by: absolute neutrophil count (ANC) ≥ 1.5 x 10⁹/L, platelets ≥ 100 x 10⁹/L, Hb >9 g/dL
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  • Electrolytes: Total calcium (corrected for serum albumin) within normal limits (ongoing requirement for bisphosphonate to control malignant hypercalcemia is not allowed but prophylactic use of bisphosphonate to prevent skeletal complication of bone metastasis is allowed); magnesium ≥ the lower limit of normal
  • Liver function: aspartate aminotransferase (AST)/serum glutamate oxaloacetate transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamate pyruvate transaminase (SGPT) ≤ 2.5 x Upper Limit of Normal (ULN) or ≤ 5.0 x ULN if liver metastases are present; serum bilirubin ≤ 1.5 x ULN in patients with known Gilbert Syndrome, total bilirubin ≤ 3 x ULN, with direct bilirubin ≤ 1.5 x ULN
  • Renal function: serum creatinine ≤ 1.5 x ULN or 24-hour clearance ≥ 50 mL/min or calculated glomerular filtration rate (GFR) of 60cc/ml using the formula of Cockroft and Gault
  • Serum amylase ≤ ULN
  • Serum lipase ≤ ULN
  • Fasting plasma glucose ≤ 120 mg/dL (6.7 mmol/L)
  • International normalized ratio (INR) ≤ 2
  • Negative serum pregnancy test within 48 hours before starting study treatment in women with childbearing potential
  • Ability and willingness to participate in the informed consent process and signing a copy of the informed consent form
  • Presence of appropriate size and site of viable tumor tissue for safe tumor biopsy collection (the biopsy is optional and requirement is only applicable to subjects considered for the expansion cohort stage of the study)
  • Ability and willingness to undergo repeat tumor biopsies (the biopsy is optional and only applicable to subjects considered for the expansion cohort stage of the study)

Who cannot join

  • Patients who have received prior treatment with a phosphatidylinositol 3-kinase (P13K) inhibitor or RAD001 (if discontinued for toxicity)
  • Patients with a known hypersensitivity to BKM120, RAD001 (including other rapalogs) or their excipients
  • Patients with untreated symptomatic brain metastases are excluded. However, patients with metastatic central nervous system (CNS) tumors may participate in this trial, if the patient is > 4 weeks from therapy completion (including radiation and/or surgery), is clinically stable at the time of study entry and is not receiving corticosteroid therapy for the brain mets.
  • Patients with acute or chronic liver, renal disease or pancreatitis
  • Patients has any of the following mood disorders as judged by the Investigator or a Psychiatrist, or who meets the cut-off score of ≥ 12 the Patient Health Questionnaire-9 (PHQ-9) or a cut-off of ≥ 15 in the Generalized Anxiety Disorder-7 (GAD-7) mood scale, respectively, or selects a positive response of '1, 2, or 3' to questions number 9 regarding potential for suicidal thoughts in the PHQ-9 (independent of the total score of the PHQ-9) :
  • 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) or patients with active severe personality disorders are not eligible. Note: for patients with psychotropic treatments ongoing at baseline, the dose and the schedule should not be modified within the previous 6 weeks prior to start of study drug.
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  • ≥ Common Toxicity Criteria for Adverse Effects (CTCAE) grade 3 anxiety
  • Note: The psychiatric judgment overrules the mood assessment questionnaire result or the investigators judgment.
  • Patient has active cardiac disease including any of the following:
  • Left ventricular ejection fraction (LVEF) < 50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO)
  • Corrected QT interval (QTc) > 480 msec on screening ECG (using the Fridericia's corrected QT interval [QTcF] formula)
  • Angina pectoris that requires the use of anti-anginal medication
  • Ventricular arrhythmias except for benign premature ventricular contractions
  • Supraventricular and nodal arrythmias requiring a pacemaker or not controlled with medication
  • Conduction abnormality requiring a pacemaker
  • Valvular disease with document compromise in cardiac function
  • Symptomatic pericarditis
  • Patient has a history of cardiac dysfunction including any of the following:
  • Myocardial infraction within the last 6 months, documented by persistent elevated cardiac enzymes or preexistent regional wall abnormalities on assessment of LVEF function
  • History of or documented congestive heart failure (New York Heart Association functional classification III-IV)
  • Documented cardiomyopathy
  • Active diarrhea ≥ CTCAE grade 2
  • Patients with clinical manifestation of uncontrolled diabetes mellitus (i.e. treated and/or with clinical signs) or steroid-induced diabetes mellitus
  • 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., granulocyte-colony stimulating factor [G-CSF], granulocyte macrophage-colony-stimulating factor [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 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. Please refer to Table 5-2 or a list of prohibited QT prolonging drugs with risk of Torsades de Pointes.
  • Patients receiving chronic treatment with steroids or another immunosuppressive agent. Note: Topical applications (e.g. for rash), inhaled sprays (e.g. for obstructive airways diseases), eye drops or local injections (e.g. intra-articular) are allowed. Patients with previously treated brain metastases, who are on stable low dose corticosteroid treatment (e.g. dexamethasone 2 mg/day, prednisolone 10 mg/day) for at least 14 days before start of study treatment are eligible.
  • 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
  • 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
  • Patients who have 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
  • 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.
  • 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. Women of child-bearing potential, defined as sexually mature women who have not undergone a hysterectomy or who have not been naturally postmenopausal for at least 12 consecutive months (i.e., who has had menses any time in the preceding 12 consecutive months), must have a negative serum pregnancy test ≤ 72 hours prior to initiating treatment.
  • Liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh class C). Note: A detailed assessment of Hepatitis B/C medical history and risk factors must be done at screening for all patients. Hepatitis B virus (HBV) DNA and hepatitis C virus (HCV) RNA polymerase chain reaction (PCR) testing are required at screening for all patients with a positive medical history based on risk factors and/or confirmation of prior HBV/HCV infection.
  • Known diagnosis of human immunodeficiency virus (HIV) infection
  • History of another malignancy within 3 years, except cured basal cell carcinoma of the skin, treated ductal carcinoma in situ (DCIS), cured early stage prostate cancer without detectable prostatic specific antigen (PSA) or excised carcinoma in situ of the cervix
  • Patients should not receive immunization with attenuated live vaccines during study period or within 1 week of study entry. Close contact with those who have received attenuated live vaccines should be avoided during treatment with everolimus. Examples of live vaccines include intranasal influenza, measles, mumps, rubella, oral polio, Bacillus Calmette-Guérin (BCG), yellow fever, varicella and TY21a typhoid vaccines.
  • Patients taking medications known to be strong CYP3A inhibitors
  • Patients who are currently treated with drugs known to be moderate and strong inhibitors or inducers of isoenzyme cytochrome P450, family 3, subfamily A (CYP3A), and the treatment cannot be discontinued or switched to a different medication prior to starting study drug.
  • 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
  • Patient is unable or unwilling to abide by the study protocol or cooperate fully with the investigator

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Winship Cancer Institute of Emory University

    Atlanta, Georgia, 30322

Other trials in United States

About this study

This study will assess the safety of combining two agents (everolimus and BKM120) for the treatment of advanced cancer arising from solid organ in patients who are no longer benefiting from or unable to withstand standard treatment of these conditions.

Read the detailed description

The purpose of this study is to study the combination of two anticancer drugs, everolimus (RAD001) and BKM120, in patients whose cancer is no longer responding to standard treatment or patients who are unable to tolerate the standard treatment for their cancer. The investigators seek to establish the safety of taking these two medications together and to determine the appropriate doses of the two drugs when given together as well as identify potential side effects when the drugs are administered together.

Another purpose of this study is to determine the effectiveness and side effects of the combination of RAD001 and BKM120 by looking at the patient's response to the treatment. The investigators want to find out what effects, good or bad, the drugs have on the patient's cancer.

This study will also look at specific biomarkers in the patient's blood and in the tumor tissue which are involved in the growth of tumor cells and determine if the levels of these biomarkers are related to the patient's response to treatment or development of side effects.

Everolimus, also known by the brand name, Afinitor, is a biologic drug approved by the Food and Drug Administration (FDA) for the treatment of kidney cancer. It works by preventing cancer cell from multiplying and it also renders them easily susceptible to death.

BKM120 is a new study drug that is being tested for its ability to treat cancer. However, it has not yet been approved by the FDA for the treatment of any specific cancer type.

Being tested
BKM120, Everolimus
Keywords
lung cancer with activated mTOR/PI3K pathway, alterations in PIK3CA, NF1, TSC1/TSC2, mTOR, KRAS, LKB1, PTEN
Medical subject headings
Lung Neoplasms, Hereditary Sensory and Autonomic Neuropathies

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BKM120Drug

    Also called Buparlisib

    BKM120 (20mg to 100mg) will be self-administered (by the patients themselves). The investigator will instruct the patient to take the study drug exactly as specified in the protocol. BKM120 will be administered on a continuous once daily dosing schedule. Patients should be instructed to take the dose of BKM120 daily in the morning, one hour after a light breakfast (morning meal) at approximately the same time each day. BKM120 should be taken with a glass of water and consumed over as short a time as possible. Patients should swallow the capsules as a whole and not chew them. Patients should continue to fast for 2 hours after the administration of each BKM120 dose.

  • EverolimusDrug

    Also called RAD001, Afinitor

    RAD001 will be self-administered (by the patients themselves). The investigator will instruct the patient to take the study drug exactly as specified in the protocol. RAD001 will be administered orally as once daily dose of 5mg or 10 mg (based on the dose cohort) continuously from study day 1 until progression of disease or unacceptable toxicity. Patients will be instructed to take RAD001 in the morning, at the same time each day.

Study groups in NCT01470209
Study groupRoleWhat they receive
Combination of BKM120 and everolimusExperimentalNot described
Receives: Drug: BKM120; Drug: Everolimus

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose limiting toxicity

    1. Grade 4 hematologic toxicity (excluding anemia) lasting more than 7 days ii. Grade 3 anemia lasting more than 7 days or requiring blood transfusion iii. Grade 4 anemia iv. Grade ≥ 3 febrile neutropenia of any duration
    2. Grade ≥ 3 nausea and or vomiting lasting more than 72 hours in spite of standard supportive therapy vi. Grade ≥ 3 non-hematologic toxicity (excluding alopecia)

    Measured: During the first cycle of treatment; approximately 4 weeks

Secondary outcomes (1)

  1. Clinical benefit rate

    Sum of complete response, partial response and stable disease

    Measured: During the entire duration of therapy estimated to be an average of 6 months for each patient

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Nov 2011 (estimated)
  2. Study startJan 2012
  3. Primary completionMay 2017
  4. Study completionMay 2017

Resources

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
43 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01470209
Sponsor's protocol ID
IRB00048549
Other IDs
WCI1925-10
Status last verified
Mar 2018
First submitted
25 Oct 2011
Last updated
19 Mar 2018
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing BKM120 and Everolimus in people with Solid Tumors and Lung Cancer, run by Emory University 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 17 inclusion and 41 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 19 Mar 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?

Dose limiting toxicity (time frame: During the first cycle of treatment; approximately 4 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01470209.

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 19 Mar 2018.

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