Thyroid CancersPhase 2BKM120NCT01830504
A Multicenter Phase II Pilot Open Label
A Phase 2 study testing BKM120 in people with Thyroid Cancers, run by Hospices Civils de Lyon at 1 site in France.
Trial summary
In France, 7-8 000 new thyroid cancer cases are diagnosed each year. Although a good overall prognosis, it is usually estimated that 10 to 20% will rescue and 5% will become metastatic. The standard treatment of advanced metastatic or recurrent thyroid cancer is limited to radioiodine therapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Thyroid Cancers
- What is being tested?
- BKM120
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 47 participants
- Where
- 1 siteFrance
- Study dates
- Apr 2013to Jan 2017
- Phase
- Phase 2
- 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
- Histologically confirmed differentiated follicular or poorly differentiated thyroid cancer
- Patients refractory to radio iodine: i.e.; absence of radioiodine uptake in at least one target lesion on a post-therapeutic whole body scan, presence of a target lesion after a cumulative radio-iodine activity of at least 600 mCi, patients with radio-iodine uptake who have progression of the disease within 12 months after radioactive iodine (RAI) treatment
- Metastatic or locally invasive disease
- Patients must have at least one site of measurable disease per RECIST (version 1.1.)
- Documented progression as per RECIST (version 1.1.) based on 2 comparative imagings performed within the last 12 months (+20%)
- Patients may have received two previous treatment with tyrosine kinase inhibitors but must be off treatment within at least 4 weeks
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- Patient has signed the informed consent before any trial related activities and according to local guidelines
- Patient (male or female) is ≥ 18 years at the day of consenting to the study
- Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 which the investigator believes is stable at the time of screening
- Patient has adequate bone marrow and organ function as defined by the following laboratory values:
- Absolute Neutrophil Count (ANC) ≥ 1.0 x 109/L
- Platelets ≥ 100 x 109/L
- Hemoglobin ≥ 9.0 g/dL
- INR ≤ 1,5
- Potassium, calcium,and magnesium within normal limits (WNL) for theinstitution
- Serum Creatinine ≤ 1.5 x ULN
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal range
- Total Serum bilirubin within normal range normal liver function test results, and absence of other contributing disease processes at the time of diagnosis
- Fasting plasma glucose (FPG) ≤ 120 mg/dL or ≤ 6.7 mmol/L
- HbA1c ≤ 8 %
- Patient has no legal protection measure
- Patient has a health coverage
Who cannot join
- Other histological subtypes of thyroid tumors: papillary, anaplastic, medullary, lymphoma or sarcoma
- Patient has received previous treatment with PI3K and/or mTOR inhibitors or AKT inhibitors,
- Patient has symptomatic central nervous system (CNS) metastases. Patients with controlled and asymptomatic CNS metastases may participate in this trial. The patient must have completed any prior local treatment for CNS metastases ≥ 28 days (including radiotherapy and/or surgery) prior to enrollment in this study
- Patient has a concurrent malignancy or malignancy within 3 years of study enrollment,
- Patient has a score ≥ 12 on the PHQ-9 questionnaire
- Patient selects a response of "1, 2 or 3" to question number 9 on the PHQ-9 questionnaire regarding potential for suicidal thoughts or ideation
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- Patient has a GAD-7 mood scale score ≥ 15
- Patient has a 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
- Patient is concurrently using other approved or investigational antineoplastic agent
- Patient who received wide field radiotherapy ≤ 4 weeks or limited field radiation for palliation ≤ 2 weeks prior to starting study drug or who have not recovered to grade 1 or better from related side effects of such therapy
- Patient has had major surgery within 14 days prior to starting study drug or has not recovered from major side effects of the surgery
- Patient has active cardiac disease or a history of cardiac dysfunction including any of the following:Unstable angina pectoris within 6 months prior to study entry,Symptomatic pericarditis,Documented myocardial infarction within 6 months prior to study entry,History of documented congestive heart failure,Documented cardiomyopathy
- Patient has a Left Ventricular Ejection Fraction (LVEF) < 50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO)
- Patient has any of the following cardiac conduction abnormalities:
- Patient is currently receiving treatment with medication that has a known risk to prolong the QT interval or inducing Torsades de Pointes, and the treatment cannot be discontinued or switched to a different medication prior to randomization.
- Patient has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of BKM120
- Patient is currently receiving increasing or chronic treatment (> 5 days) with corticosteroids or another immunosuppressive agent, as chronic administration of corticosteroids (> 5 days) can induce CYP3A4 The following uses of corticosteroids are permitted: single doses; topical applications, inhaled sprays, eye drops or local injections
- Patient has any other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment contraindicate patient participation in the clinical study
- Patient has a history of non-compliance to medical regimen or inability to grant consent
- Patient is currently receiving treatment with drugs known to be moderate and strong inhibitors or inducers of isoenzyme CYP3A, The patient must have discontinued strong inducers for at least one week and must have discontinued strong inhibitors before the treatment is initiated. Switching to a different medication prior to entry in the treatment phase is allowed.
- Patient has a known history of HIV (testing not mandatory) infection
- Pregnant or nursing (lactating) woman where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive beta hCG laboratory test (> 5 mIU/mL)
- Patient who does not apply highly effective contraception during the study and through the duration as defined below after the final dose of study treatment.
- Patient has a known hypersensitivity to any of the excipients of BKM120
- Patient has not recovered to grade 1 or better (except alopecia) from related side effects of any prior antineoplastic therapy
- Patient is currently receiving warfarin or other coumarin derived anti-coagulant, for treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight heparin (LMWH), or fondaparinux is allowed
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Multicenter Phase II Pilot Open Label Study to Evaluate the Efficacy and Safety of BKM120 in the Treatment of Patients With Advanced or Metastatic Differentiated Thyroid Cancers
In France, 7-8 000 new thyroid cancer cases are diagnosed each year. Although a good overall prognosis, it is usually estimated that 10 to 20% will rescue and 5% will become metastatic.
The standard treatment of advanced metastatic or recurrent thyroid cancer is limited to radioiodine therapy. It is estimated that 30 to 50% of patients will become resistant to radio iodine. Treatments options are limited in these refractory thyroid patients and long term survival is estimated to less than 10%. Nowadays, no drug is approved in this indication.
Read more
The recent explosion in knowledge in tumour biology and the identification of potential biological targets in thyroid cancer led to several clinical trials with targeted therapies, mainly focused on TKI inhibitors targeting the MAPkinase pathway and/or VEGF. Preliminary results were encouraging in papillary thyroid tumors.
Follicular (FTC) and poorly differentiated thyroid (PDTC) cancers account for 10% of thyroid cancer but 20-25% of cancers diagnosed at an advanced stage and near 50% of metastatic refractory thyroid cancers. These cancers with an aggressive behavior represent a major cause of death from thyroid cancer. In these subtypes, targeted therapies gave disappointing results. This may be related to the mutational profile of these tumors which is different from that of papillary cancers. Aberrant activation of the phosphatidylinositol-3-kinase (PI3K)/AKT pathway is thought to play a fundamental role in thyroid tumorigenenesis of follicular and poorly differentiated thyroid cancers. Many genetic alterations have been, recently, identified in this pathway. PIK3CA mutations are found in 10-15% of FTC and can also occur in metastases derived from PDTC. Amplification/genomic copy gain of the PIK3CA has been identified in 24% of FTC and 42% of PDTC. Epigenetic inactivation of PTEN which negatively regulates PI3K has been shown in FTC. Moreover, RAS mutations observed in 20-40% of FTC and PDTC can activate the PI3K/AKT by interacting with the RAS-binding site of the P110 catalytic subunit of PI3K.
Due to the high frequency of activation of PI3K and downstream effectors in progressive, recurrent and poorly differentiated cancers, inhibition of the PI3K signaling pathway with BKM120, a potent pan class I PI3K inhibitor, represents a particularly relevant therapeutic target and should be properly evaluated in advanced follicular and poorly differentiated thyroid carcinomas
Read the detailed description
The primary objective of the study will be to determine efficacy of BKM120 as measured by the progression free survival (PFS rate) at 6 months in patients with progressive, metastatic, refractory, follicular or poorly differentiated thyroid cancers.
- Conditions
- Thyroid Cancers
- Being tested
- BKM120
- Keywords
- thyroid cancers, refractory, PI3K inhibitor
- Medical subject headings
- Thyroid Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BKM120Drug
BKM 120, 100 mg/day continuously. For patients who do not tolerate the protocol-specified dosing schedule, dose adjustments are permitted in order to allow the patient to continue the study treatment. Dose level -1 : 80 mg/day continuously, Dose level -2 : 80 mg/day 5 days out of 7. All dose modifications, interruptions or discontinuations must be based on the worst preceding toxicity as graded by the NCI Clinical Toxicity Criteria (NCI-CTCAE version 4.03.
A change from continuous schedule to intermittent (5 days out of 7) must be preceded by 2 days without treatment.
| Study group | Role | What they receive |
|---|---|---|
| NVP-BKM120 (BKM120) PI3K inhibitor | Experimental | Not described Receives: Drug: BKM120 |
What is being measured
The primary outcome is the main question the study is designed to answer.
progression-free survival (PFS)
The progression-free survival is defined as a lack of objective tumor progression and death. Tumor progression is documented by the CT or MRI scans. Progression is defined according to RECIST criteria (version 1.1.).
Measured: at 6 months after the onset of the treatment
Secondary outcomes (4)
progression-free survival (PFS)
Measured: PFS at 12 months after the onset of the treatment
Objective tumor response (CR and PR)
according to RECIST criteria (version 1.1.) and validated by a central review committee.
Measured: at 6 months after the onset of the treatment
Overall survival
Overall survival (defined as the time from start of study treatment to the date of death due to any cause)
Measured: at 6 months after the onset of the treatment
safety and tolerance of BKM120 of BKM120: monitoring and recording AE and SAE, monitoring of hematology, blood chemistry and urine values, vital signs, physical examinations, skin, cardiac assessments and mood evaluation.
Safety and tolerability will be assessed according to the NIH/NCI CTC (V4.0). Care will be taken to the monitoring of haematology, kidney function, liver function, endocrin/metabolic function, cardiac function, mood and rash evaluation.
Blood chemistry and urine will be considered. The others assessment will be: physical examination, ECOG performance status, body weight, vital signs, PHQ9 and GAD7 questionnaires, ECG and CT or MRI scans.
For patients who do not tolerate the protocol-specified dosing schedule, dose modification and/or dose interruption are permitted.
Measured: After the patient has provided informed consent and until 4 weeks after the patient has stopped study participation. Assessments are performed at least every month during the first year, every 3 month until 12 months and every 4 months after this period.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2013 (estimated)
- Study startApr 2013
- Primary completionApr 2013
- Study completionJan 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Thyroid CancersStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 47 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Françoise BORSON-CHAZOT, PUPH, Study director, Hospices Civils de Lyon
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01830504
- Sponsor's protocol ID
- 2012-748
- Acronym
- BKM120
- Status last verified
- Oct 2016
- First submitted
- 4 Apr 2013
- Last updated
- 5 Oct 2016
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Borson-Chazot F, Dantony E, Illouz F, Lopez J, Niccoli P, Wassermann J, Do Cao C, Leboulleux S, Klein M, Tabarin A, Eberle MC, Benisvy D, de la Fouchardiere C, Bournaud C, Lasolle H, Delahaye A, Rabilloud M, Lapras V, Decaussin-Petrucci M, Schlumberger M. Effect of Buparlisib, a Pan-Class I PI3K Inhibitor, in Refractory Follicular and Poorly Differentiated Thyroid Cancer. Thyroid. 2018 Sep;28(9):1174-1179. doi: 10.1089/thy.2017.0663.
PubMed 30105951
Study at a glance
From the registry record, last updated by the sponsor on 5 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter Phase II Pilot Open Label Study to Evaluate the Efficacy and Safety of BKM120 in the Treatment of Patients With Advanced or Metastatic Differentiated Thyroid Cancers
- ClinicalTrials.gov ID
- NCT01830504
- Acronym / sponsor ID
- BKM120 / 2012-748
- Conditions
- Thyroid Cancers
- Keywords
- thyroid cancers, refractory, PI3K inhibitor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 47 participants (actual)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- Apr 2013
- Primary completion
- Apr 2013 (actual)
- Study completion
- Jan 2017 (estimated)
- First posted
- 12 Apr 2013 (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.
In France, 7-8 000 new thyroid cancer cases are diagnosed each year. Although a good overall prognosis, it is usually estimated that 10 to 20% will rescue and 5% will become metastatic.
The standard treatment of advanced metastatic or recurrent thyroid cancer is limited to radioiodine therapy. It is estimated that 30 to 50% of patients will become resistant to radio iodine. Treatments options are limited in these refractory thyroid patients and long term survival is estimated to less than 10%. Nowadays, no drug is approved in this indication.
The recent explosion in knowledge in tumour biology and the identification of potential biological targets in thyroid cancer led to several clinical trials with targeted therapies, mainly focused on TKI inhibitors targeting the MAPkinase pathway and/or VEGF. Preliminary results were encouraging in papillary thyroid tumors.
Follicular (FTC) and poorly differentiated thyroid (PDTC) cancers account for 10% of thyroid cancer but 20-25% of cancers diagnosed at an advanced stage and near 50% of metastatic refractory thyroid cancers. These cancers with an aggressive behavior represent a major cause of death from thyroid cancer. In these subtypes, targeted therapies gave disappointing results. This may be related to the mutational profile of these tumors which is different from that of papillary cancers. Aberrant activation of the phosphatidylinositol-3-kinase (PI3K)/AKT pathway is thought to play a fundamental role in thyroid tumorigenenesis of follicular and poorly differentiated thyroid cancers. Many genetic alterations have been, recently, identified in this pathway. PIK3CA mutations are found in 10-15% of FTC and can also occur in metastases derived from PDTC. Amplification/genomic copy gain of the PIK3CA has been identified in 24% of FTC and 42% of PDTC. Epigenetic inactivation of PTEN which negatively regulates PI3K has been shown in FTC. Moreover, RAS mutations observed in 20-40% of FTC and PDTC can activate the PI3K/AKT by interacting with the RAS-binding site of the P110 catalytic subunit of PI3K.
Due to the high frequency of activation of PI3K and downstream effectors in progressive, recurrent and poorly differentiated cancers, inhibition of the PI3K signaling pathway with BKM120, a potent pan class I PI3K inhibitor, represents a particularly relevant therapeutic target and should be properly evaluated in advanced follicular and poorly differentiated thyroid carcinomas
Detailed description
The primary objective of the study will be to determine efficacy of BKM120 as measured by the progression free survival (PFS rate) at 6 months in patients with progressive, metastatic, refractory, follicular or poorly differentiated thyroid cancers.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| NVP-BKM120 (BKM120) PI3K inhibitor | Experimental | Drug: BKM120 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Histologically confirmed differentiated follicular or poorly differentiated thyroid cancer
- Patients refractory to radio iodine: i.e.; absence of radioiodine uptake in at least one target lesion on a post-therapeutic whole body scan, presence of a target lesion after a cumulative radio-iodine activity of at least 600 mCi, patients with radio-iodine uptake who have progression of the disease within 12 months after radioactive iodine (RAI) treatment
- Metastatic or locally invasive disease
- Patients must have at least one site of measurable disease per RECIST (version 1.1.)
- Documented progression as per RECIST (version 1.1.) based on 2 comparative imagings performed within the last 12 months (+20%)
Key exclusion criteria (26 listed)
- Other histological subtypes of thyroid tumors: papillary, anaplastic, medullary, lymphoma or sarcoma
- Patient has received previous treatment with PI3K and/or mTOR inhibitors or AKT inhibitors,
- Patient has symptomatic central nervous system (CNS) metastases. Patients with controlled and asymptomatic CNS metastases may participate in this trial. The patient must have completed any prior local treatment for CNS metastases ≥ 28 days (including radiotherapy and/or surgery) prior to enrollment in this study
- Patient has a concurrent malignancy or malignancy within 3 years of study enrollment,
- Patient has a score ≥ 12 on the PHQ-9 questionnaire
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 |
|---|---|---|
| BKM120BKM 120, 100 mg/day continuously. For patients who do not tolerate the protocol-specified dosing schedule, dose adjustments are permitted in order to allow the patient to continue the study treatment. Dose level -1 : 80 mg/day continuously, Dose level -2 : 80 mg/day 5 days out of 7. All dose modifications, interruptions or discontinuations must be based on the worst preceding toxicity as graded by the NCI Clinical Toxicity Criteria (NCI-CTCAE version 4.03. A change from continuous schedule to intermittent (5 days out of 7) must be preceded by 2 days without treatment. | Drug | NVP-BKM120 (BKM120) PI3K inhibitor |
Primary outcome
progression-free survival (PFS)
Time frame: at 6 months after the onset of the treatment
The progression-free survival is defined as a lack of objective tumor progression and death. Tumor progression is documented by the CT or MRI scans. Progression is defined according to RECIST criteria (version 1.1.).
4 secondary outcomes
progression-free survival (PFS)
Time frame: PFS at 12 months after the onset of the treatment
Objective tumor response (CR and PR)
Time frame: at 6 months after the onset of the treatment
Overall survival
Time frame: at 6 months after the onset of the treatment
safety and tolerance of BKM120 of BKM120: monitoring and recording AE and SAE, monitoring of hematology, blood chemistry and urine values, vital signs, physical examinations, skin, cardiac assessments and mood evaluation.
Time frame: After the patient has provided informed consent and until 4 weeks after the patient has stopped study participation. Assessments are performed at least every month during the first year, every 3 month until 12 months and every 4 months after this period.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Oct 2016.
- Derived from this study: PubMed 30105951Borson-Chazot F, Dantony E, Illouz F, Lopez J, Niccoli P, Wassermann J, Do Cao C, Leboulleux S, Klein M, Tabarin A, Eberle MC, Benisvy D, de la Fouchardiere C, Bournaud C, Lasolle H, Delahaye A, Rabilloud M, Lapras V, Decaussin-Petrucci M, Schlumberger M. Effect of Buparlisib, a Pan-Class I PI3K Inhibitor, in Refractory Follicular and Poorly Differentiated Thyroid Cancer. Thyroid. 2018 Sep;28(9):1174-1179. doi: 10.1089/thy.2017.0663.
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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.
Françoise BORSON-CHAZOT, PUPH study director
Hospices Civils de Lyon
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing BKM120 in people with Thyroid Cancers, run by Hospices Civils de Lyon at 1 site in France.
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 22 inclusion and 26 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: status not confirmed, as of the sponsor's last update on 5 Oct 2016. 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 France. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
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?
progression-free survival (PFS) (time frame: at 6 months after the onset of the treatment). 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 NCT01830504, which also lists 1 linked publication.
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 5 Oct 2016.