Non Castrate Metastatic Prostate CancerPhase 1NCMPC-BKMNCT02487823
Dose Finding Study of BKM 120 in Combination With LH-RH Agonists and Bicalutamide in Men With Non Castrate Metastatic Prostate Cancer
A Phase 1 study testing BKM120 in combination with LH-RH agonists (suprefact) and bicalutamide in people with Non Castrate Metastatic Prostate Cancer, run by Institut Paoli-Calmettes at 1 site in France.
Trial summary
To determine the maximum-tolerated dose (MTD) of BKM120 when administered orally in combination with daily bicalutamide and LH-RH agonists to men with non castrate metastatic prostate cancer. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- Non Castrate Metastatic Prostate Cancer
- What is being tested?
- BKM120 in combination with LH-RH agonists (suprefact) and bicalutamide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteFrance
- Study dates
- Oct 2014to Nov 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
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed Informed Consent Form (ICF) prior to screening
- Male patients (≥ 18 years)
- WHO performance status ≤ 2
- Histologically-confirmed adenocarcinoma of the prostate
- Patients with non castrate metastatic prostate cancer, with radiological metastatic disease ; patients with metastatic disease is documented on a Pet-Scan to choline is also eligible
- No previous chemotherapy treatment during the metastatic disease
Show all 19Show fewer
- Neoadjuvant or adjuvant androgen deprivation therapy (ADT) treatment or for rising PSA is permitted if the ADT have been stopped for at least one year without metastasis or PSA increase during this time
- LH-RH agonists and bicalutamide had to began ≥ 28 days before registration
- Minimum pre treatment PSA > 5 ng/ml
- 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 ≤ 2
- Potassium, calcium, magnesium within normal limits for the institution
- Serum Creatinine ≤ 1.5 x ULN
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) within normal range (or ≤ 3.0 x 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)
- Fasting plasma glucose (FPG) ≤ 120 mg/dL or ≤ 6.7 mmol/L 11. Agree to use effective contraception during the study and for at least 16 weeks after discontinuation 12. Patient is able to swallow and retain oral medication
Who cannot join
- Patients eligible for this study must not meet any of the following criteria:
- Patient has received previous treatment with PI3K and/or mTOR inhibitors
- Patient has a concurrent malignancy or has a malignancy within 3 years of study enrollment, (with the exception of adequately treated basal or squamous cell carcinoma or non-melanomatous skin cancer)
- ADT > 3 months
- Patient has any of the following mood disorders as judged by the Investigator or a Psychiatrist, or meets the cut-off score of ≥ 12 in the PHQ-9 or a cut-off of ≥ 15 in the GAD-7 mood scale, respectively, or selects a positive response of '1, 2, or 3' to question number 9 regarding potential for suicidal thoughts ideation 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 (defined according to DSM-IV) 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
Show all 28Show fewer
- ≥ CTCAE grade 3 anxiety
- Patient is concurrently using other approved or investigational antineoplastic agent Patient has received pelvic and/or para-aortic radiotherapy ≤ 28 days prior to enrollment in this study or has not recovered from side effects of such therapy at the time of initiation of screening procedures Patient has had major surgery within 28 days prior to starting study drug or has not recovered from major side effects of the surgery Patient has poorly controlled diabetes mellitus (HbA1c > 8 %) Patient with uncontrolled hypertension
- 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)
- QTc > 480 msec on screening ECG (using the 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 documented compromise in cardiac function
- Symptomatic pericarditis
- Patient has a history of cardiac dysfunction including any of the following:
- Myocardial infarction within the last 6 months, documented by persistent elevated cardiac enzymes or persistent regional wall abnormalities on assessment of LVEF function
- History of documented congestive heart failure (New York Heart Association functional classification III-IV)
- Documented cardiomyopathy
- Patient is currently receiving treatment with QT prolonging medication known to have a risk to induce Torsades de Pointes, and the treatment cannot be discontinued or switched to a different medication prior to starting study drug
- Patient has 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)
- Patient receiving chronic treatment with steroids or another immunosuppressive agent Note: Topical applications (e.g., rash), inhaled sprays (e.g., obstructive airways diseases), eye drops or local injections (e.g., intra-articular) are allowed. Patients with previously treated brain metastases, who are on a stable low dose corticosteroids treatment (e.g., dexamethasone 2 mg/day, prednisolone 10 mg/day) for at least 14 days before start of study treatment, are eligible
- Patient has other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment contraindicate her participation in the clinical study (e.g.,chronic pancreatitis, active chronic hepatitis etc.)
- Patient has a history of non-compliance to medical regimen
- Patient is currently being 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. Please refer to annex 9 for a list of prohibited CYP3A inhibitors and inducers Note: the oral anti-diabetic drugs troglitazone and pioglitazone are CYP3A inducers
- Patient has a known history of HIV (testing not mandatory) infection
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase Ib Dose Finding Study of BKM 120 in Combination With LH-RH Agonists and Bicalutamide in Men With Non Castrate Metastatic Prostate Cancer
To determine the maximum-tolerated dose (MTD) of BKM120 when administered orally in combination with daily bicalutamide and LH-RH agonists to men with non castrate metastatic prostate cancer.
Read the detailed description
Prostate cancer is the second leading cause of cancer and the third cause of death in male. Majority of patients had local disease that is cured by local treatment. Metastases are rare at the time of diagnosis but may occur after failure of local treatment (SEER).
Recommended treatment for non castrate metastatic prostate cancer (NCMPC) is castration by orchiectomy or medical castration by LH-RH (luteinizing hormone-releasing hormone) agonists alone and or combined androgen blockage with LH-RH agonists and anti androgen. Immediate treatment versus deferred treatment improve specific survival for advanced prostatic cancer : initial results of the Medical Research Council trial.
Continuous castration is superior to intermittent one with a median survival of 49 months. Chemotherapy combined with castration demonstrate a survival improvement compared to castration alone for high volume disease defined by visceral involvement and or 4 or more bone metastatis with almost one apendicular metastasis. For low volume disease or non selected metastatic hormone sensitive prostate cancer, Docetaxel demonstrated no survival benefit evaluated in a recent phase III trial (Sweeney C et al abs ASCO 2014).
However, most patients showing an initial response to hormonal therapy for advanced prostate cancer will progress to a castration-resistant phase of the disease with a much poorer prognosis. Median duration to androgen deprivation is 24 to 36 months, after patients become castrate resistant and docetaxel and other hormonal therapy like abiraterone and enzalutamide demonstrate survival improvement in castrate resistant prostate cancer.
Despite the considerable progress made with new agents such as abiraterone acetate or MDV3100 in metastatic castration resistant prostate cancer (mCRPC), new therapies are critical to improve castration sensitivity.
Understanding the mechanisms of resistance to AR and identifying directed new therapies is a real challenge in this situation.
Prostate cancer is characterized by its dependence on AR and its frequent activation of the Phosphatidylinositol-3-kinase (PI3K) pathway. Besides the resistance mediated by the mutation in the AR, among the non-steroid alternative pathways two major pathways have been associated with AR activation and CRPC, namely Ras/Raf/MEK/ERK and PI3K/AKT. More specifically a genomic profiling of human prostate cancer was recently reported where 42% of primary and 100% of the metastatic lesions studied had upregulated PI3K signaling mostly via loss of phosphatase activity such as PTEN (Phosphatase and tensin homolog) or INPP4B (inositol polyphosphate 4-phosphatase type II).
Dysregulation of the PI3K/PTEN pathway has also been associated with resistance to conventional antiandrogen therapies. Preclinical data support the potential for a reciprocal negative feedback between the AR and PI3K pathway.
Development of castration resistance is multifactorel including weak antagonist binding affi nity to AR, up-regulation of AR co-stimulatory pathways and increased intratumoural androgen levels as a result of intracrine androgen, as well as partial agonists properties of antiandrogens when AR is overexpressed.
- Conditions
- Non Castrate Metastatic Prostate Cancer
- Being tested
- BKM120 in combination with LH-RH agonists (suprefact) and bicalutamide
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BKM120 in combination with LH-RH agonists (suprefact) and bicalutamideDrug
Also called BKM120, LH-RH agonists (suprefact) and bicalutamide (casodex)
BKM 120, LH-RH agonists and Bicalutamide
| Study group | Role | What they receive |
|---|---|---|
| BKM 120 (60 mg) | Experimental | BKM120 (60 mg) in combination with LH-RH agonists and bicalutamide Receives: Drug: BKM120 in combination with LH-RH agonists (suprefact) and bicalutamide |
| BKM 120 (80 mg) | Experimental | BKM120 (80 mg) in combination with LH-RH agonists and bicalutamide Receives: Drug: BKM120 in combination with LH-RH agonists (suprefact) and bicalutamide |
| BKM 120 (100 mg) | Experimental | BKM120 (100 mg) in combination with LH-RH agonists and bicalutamide Receives: Drug: BKM120 in combination with LH-RH agonists (suprefact) and bicalutamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determine the maximum-tolerated dose (MTD) of BKM120 when administered orally in combination with daily bicalutamide and LH-RH agonists to men with non castrate metastatic prostate cancer
Measured: Patient follow-up done until progression, or until 6 months after the end of treatment
Secondary outcomes (1)
Assess the efficacy of daily oral BKM120 in combination with LH-RH agonists and bicalutamide in men with NCMPC as measured by the overall rate and free survival of biological or clinical progression (composite measures).
Measured: Free survival of biological or clinical progression an expected average 30 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jul 2015 (estimated)
- Study startOct 2014
- Primary completionNov 2017
- Study completionNov 2017
Why it stopped: Defect of recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non Castrate Metastatic Prostate CancerStudies of the same condition, open and under way.
- More trials run by Institut Paoli-CalmettesThe 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
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Institut Paoli-Calmettes
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02487823
- Sponsor's protocol ID
- NCMPC-BKM-IPC 2012-009
- Acronym
- NCMPC-BKM
- Status last verified
- Oct 2017
- First submitted
- 25 Jun 2015
- Last updated
- 17 Nov 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase Ib Dose Finding Study of BKM 120 in Combination With LH-RH Agonists and Bicalutamide in Men With Non Castrate Metastatic Prostate Cancer
- ClinicalTrials.gov ID
- NCT02487823
- Acronym / sponsor ID
- NCMPC-BKM / NCMPC-BKM-IPC 2012-009
- Conditions
- Non Castrate Metastatic Prostate Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Defect of recruitment
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Institut Paoli-CalmettesUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- Oct 2014
- Primary completion
- Nov 2017 (actual)
- Study completion
- Nov 2017 (actual)
- First posted
- 2 Jul 2015 (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.
To determine the maximum-tolerated dose (MTD) of BKM120 when administered orally in combination with daily bicalutamide and LH-RH agonists to men with non castrate metastatic prostate cancer.
Detailed description
Prostate cancer is the second leading cause of cancer and the third cause of death in male. Majority of patients had local disease that is cured by local treatment. Metastases are rare at the time of diagnosis but may occur after failure of local treatment (SEER).
Recommended treatment for non castrate metastatic prostate cancer (NCMPC) is castration by orchiectomy or medical castration by LH-RH (luteinizing hormone-releasing hormone) agonists alone and or combined androgen blockage with LH-RH agonists and anti androgen. Immediate treatment versus deferred treatment improve specific survival for advanced prostatic cancer : initial results of the Medical Research Council trial.
Continuous castration is superior to intermittent one with a median survival of 49 months. Chemotherapy combined with castration demonstrate a survival improvement compared to castration alone for high volume disease defined by visceral involvement and or 4 or more bone metastatis with almost one apendicular metastasis. For low volume disease or non selected metastatic hormone sensitive prostate cancer, Docetaxel demonstrated no survival benefit evaluated in a recent phase III trial (Sweeney C et al abs ASCO 2014).
However, most patients showing an initial response to hormonal therapy for advanced prostate cancer will progress to a castration-resistant phase of the disease with a much poorer prognosis. Median duration to androgen deprivation is 24 to 36 months, after patients become castrate resistant and docetaxel and other hormonal therapy like abiraterone and enzalutamide demonstrate survival improvement in castrate resistant prostate cancer.
Despite the considerable progress made with new agents such as abiraterone acetate or MDV3100 in metastatic castration resistant prostate cancer (mCRPC), new therapies are critical to improve castration sensitivity.
Understanding the mechanisms of resistance to AR and identifying directed new therapies is a real challenge in this situation.
Prostate cancer is characterized by its dependence on AR and its frequent activation of the Phosphatidylinositol-3-kinase (PI3K) pathway. Besides the resistance mediated by the mutation in the AR, among the non-steroid alternative pathways two major pathways have been associated with AR activation and CRPC, namely Ras/Raf/MEK/ERK and PI3K/AKT. More specifically a genomic profiling of human prostate cancer was recently reported where 42% of primary and 100% of the metastatic lesions studied had upregulated PI3K signaling mostly via loss of phosphatase activity such as PTEN (Phosphatase and tensin homolog) or INPP4B (inositol polyphosphate 4-phosphatase type II).
Dysregulation of the PI3K/PTEN pathway has also been associated with resistance to conventional antiandrogen therapies. Preclinical data support the potential for a reciprocal negative feedback between the AR and PI3K pathway.
Development of castration resistance is multifactorel including weak antagonist binding affi nity to AR, up-regulation of AR co-stimulatory pathways and increased intratumoural androgen levels as a result of intracrine androgen, as well as partial agonists properties of antiandrogens when AR is overexpressed.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| BKM 120 (60 mg) | Experimental | Drug: BKM120 in combination with LH-RH agonists (suprefact) and bicalutamideBKM120 (60 mg) in combination with LH-RH agonists and bicalutamide |
| BKM 120 (80 mg) | Experimental | Drug: BKM120 in combination with LH-RH agonists (suprefact) and bicalutamideBKM120 (80 mg) in combination with LH-RH agonists and bicalutamide |
| BKM 120 (100 mg) | Experimental | Drug: BKM120 in combination with LH-RH agonists (suprefact) and bicalutamideBKM120 (100 mg) in combination with LH-RH agonists and bicalutamide |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Signed Informed Consent Form (ICF) prior to screening
- Male patients (≥ 18 years)
- WHO performance status ≤ 2
- Histologically-confirmed adenocarcinoma of the prostate
- Patients with non castrate metastatic prostate cancer, with radiological metastatic disease ; patients with metastatic disease is documented on a Pet-Scan to choline is also eligible
Key exclusion criteria (28 listed)
- Patients eligible for this study must not meet any of the following criteria:
- Patient has received previous treatment with PI3K and/or mTOR inhibitors
- Patient has a concurrent malignancy or has a malignancy within 3 years of study enrollment, (with the exception of adequately treated basal or squamous cell carcinoma or non-melanomatous skin cancer)
- ADT > 3 months
- Patient has any of the following mood disorders as judged by the Investigator or a Psychiatrist, or meets the cut-off score of ≥ 12 in the PHQ-9 or a cut-off of ≥ 15 in the GAD-7 mood scale, respectively, or selects a positive response of '1, 2, or 3' to question number 9 regarding potential for suicidal thoughts ideation in the PHQ-9 (independent of the total score of the PHQ-9):
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 |
|---|---|---|
| BKM120 in combination with LH-RH agonists (suprefact) and bicalutamideAlso: BKM120, LH-RH agonists (suprefact) and bicalutamide (casodex)BKM 120, LH-RH agonists and Bicalutamide | Drug | BKM 120 (100 mg), BKM 120 (60 mg), BKM 120 (80 mg) |
Primary outcome
Determine the maximum-tolerated dose (MTD) of BKM120 when administered orally in combination with daily bicalutamide and LH-RH agonists to men with non castrate metastatic prostate cancer
Time frame: Patient follow-up done until progression, or until 6 months after the end of treatment
1 secondary outcome
Assess the efficacy of daily oral BKM120 in combination with LH-RH agonists and bicalutamide in men with NCMPC as measured by the overall rate and free survival of biological or clinical progression (composite measures).
Time frame: Free survival of biological or clinical progression an expected average 30 months
Results and safety
The study was stopped early (reason given: Defect of recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Nov 2017.
- official web site of the sponsorLink provided by the sponsor.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 in combination with LH-RH agonists (suprefact) and bicalutamide in people with Non Castrate Metastatic Prostate Cancer, run by Institut Paoli-Calmettes 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 19 inclusion and 28 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: stopped early, as of the sponsor's last update on 17 Nov 2017. 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 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 was stopped early (reason given: Defect of recruitment). 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?
Determine the maximum-tolerated dose (MTD) of BKM120 when administered orally in combination with daily bicalutamide and LH-RH agonists to men with non castrate metastatic prostate cancer (time frame: Patient follow-up done until progression, or until 6 months after the end of 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 17 Nov 2017.