Clinical Trials Logo

Clinical Trial Details — Status: Withdrawn

Administrative data

NCT number NCT02035124
Other study ID # SCRI GU 79
Secondary ID
Status Withdrawn
Phase Phase 2
First received January 10, 2014
Last updated February 10, 2016
Start date April 2014
Est. completion date January 2015

Study information

Verified date February 2016
Source SCRI Development Innovations, LLC
Contact n/a
Is FDA regulated No
Health authority United States: Food and Drug Administration
Study type Interventional

Clinical Trial Summary

Although there have been advances in the treatment of patients with metastatic castrate-resistant prostate cancer (mCRPC), all patients eventually develop resistance to available therapy. Docetaxel is the accepted first-line agent followed by cabazitaxel in the post-docetaxel phase. In this study the investigators propose to evaluate BKM120, a PI3K inhibitor, with cabazitaxel in the treatment of patients with advanced prostate cancer.


Description:

This study will be conducted in two parts. In a lead-in cohort, the feasibility and safety of administering BKM120 with a standard dose of cabazitaxel will be assessed. If safety is confirmed, a subsequent Phase II portion will assess the activity of the combination in patients with mCRPC previously treated with docetaxel. The treatment will consist of 3-week (21-day) cycles.

The ultimate purpose of this study will be to determine progression-free survival, response rate, disease control rate and overall survival of patients treated with the combination regimen and compare outcomes to historical results with single-agent cabazitaxel.


Recruitment information / eligibility

Status Withdrawn
Enrollment 0
Est. completion date January 2015
Est. primary completion date January 2015
Accepts healthy volunteers No
Gender Male
Age group 18 Years and older
Eligibility Inclusion Criteria:

1. Adenocarcinoma of the prostate confirmed histologically.

2. Metastatic disease confirmed by biopsy or imaging studies.

3. Patients must have received treatment with docetaxel as the only previous chemotherapy regimen. In addition, previous treatment with hormonal agents and/or immune therapy is allowed (e.g., abiraterone). (Previous treatment with MDV3100 will also be allowed.)

4. Patients must be castrate-resistant (i.e. developed progression of metastases following surgical castration or during medical androgen ablation therapy) with documented castrate levels of testosterone (<50 ng/dl).

5. Patients receiving medical castration therapy with gonadotropin-releasing hormone (GnRH) analogues should continue this treatment during this study.

6. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 to 2.

7. Patient must have progressive metastatic prostate cancer by at least 1 of the following criteria:

- Soft tissue disease progression defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

- Bone scan progression defined by 2 or more new lesions on bone scan.

- Prostate specific antigen (PSA) progression is determined by a minimum of three rising PSA levels with an interval of =1 week between each determination. The screening PSA measurement (documenting progression) must be =2 ng/mL.

8. Screening PSA =2 ng/mL.

9. Adequate hematologic, renal and hepatic function:

10. Adequate serum chemistries.

11. Ability to swallow and retain oral medication.

12. Life expectancy of =6 months.

13. Patients must be =18 years of age.

14. Patients entering this study must be willing to provide tissue from a previous tumor biopsy or 15 unstained slides (if available) for correlative testing. If tissue is not available, a patient will still be eligible for enrollment into the study.

15. Ability to understand the nature of this study and give written informed consent.

Exclusion Criteria:

1. Previous treatment with PI3K inhibitors.

2. Known hypersensitivity to BKM120 or polysorbate-80 or any of the excipients or taxanes.

3. Use of an investigational drug =21 days or 5 half-lives (whichever is shorter) prior to the first dose of BKM120. For investigational drugs for which 5 half-lives is =21 days, a minimum of 10 days between termination of the investigational drug and administration of BKM120 is required.

4. Previous chemotherapy with any agent other than docetaxel. All patients must be =28 days after their most recent chemotherapy and have recovered from side effects.

5. Patient has received wide field radiotherapy (including therapeutic radioisotopes such as strontium 89) =28 days or limited field radiation for palliation =7 days prior to starting study drug or has not recovered from side effects of such therapy.

6. Major surgical procedures =28 days of beginning study drug, or minor surgical procedures =7 days. No waiting required following port-a-cath placement.

7. Clinical significant peripheral neuropathy (defined as CTCAE v4.0 Grade =2) regardless of causality.

8. Mood disorders as judged by the Investigator or a Psychiatrist, or who meets the cut-off score of =12 in the Patient Health Questionnaire (PHQ)-9 or a cut-off score of = 15 in the Generalized Anxiety Disorder (GAD)-7 mood scale, respectively, or selects a positive response of '1, 2, or 3' to question 9 regarding potential for suicidal thoughts in the PHQ-9 (independent of the total score or the PHQ-9)

- anxiety or depression = Grade 3

- 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, 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

9. Previously untreated brain metastases. Patients who have received radiation or surgery for brain metastases are eligible if there is no evidence of central nervous system (CNS) disease progression, and at least 28 days (4 weeks) have elapsed since treatment. Patients are not permitted to receive enzyme inducing anti-epileptic drugs (EIAEDs) during the study and should not be receiving chronic corticosteroid therapy for CNS metastases.

10. Leptomeningeal metastases or spinal cord compression due to disease.

11. Acute or chronic liver, renal disease or pancreatitis.

12. Uncontrolled diabetes mellitus. Type II diabetics are eligible if they require only oral hypoglycemic agents and fasting blood glucose level is =120. Type I diabetics are eligible if HbAlc is <8.

13. Presence of active gastrointestinal (GI) disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of oral therapy (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea Grade =2, and malabsorption syndrome).

14. Any of the following cardiac diseases currently or within the last 6 months:

- Left Ventricular Ejection Fraction (LVEF) <50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO)

- QTc > 480 ms on screening ECG

- Unstable angina pectoris

- Congestive heart failure (New York Heart Association [NYHA] = Grade 2

- Acute myocardial infarction

- Conduction abnormality not controlled with pacemaker or medication

- Significant ventricular or supraventricular arrhythmias (Patients with chronic rate-controlled atrial fibrillation in the absence of other cardiac abnormalities are eligible.)

- Valvular disease with significant compromise in cardiac function.

15. Family history of congenital long or short QT, or known history of QT/QTc prolongation or Torsades de Pointes (TdP). Patients who are currently receiving treatment with medication that has the potential to prolong the QT interval or induce TdP and the treatment cannot either be discontinued or switched to a different medication prior to starting study treatment.

16. Inadequately controlled hypertension (i.e., SBP>180 mmHg or DBP>100mmHg). (Patients with values above these levels must have their BP controlled with medication prior to starting treatment)

17. Patient receiving chronic treatment with systemic steroids or another immunosuppressive agent at the start of study treatment.

Note: Topical applications (e.g. rash), inhaled sprays (e.g. obstructive airways diseases), eye drops or local injections (e.g. intra-articular) are allowed.

18. Patients receiving drugs known to be moderate and strong inhibitors or inducers or isoenzyme cytochrome P450 (CYP) 3A (CYP3A) that cannot be discontinued or switched to different medication prior to starting study drug.

19. Patients who have taken herbal medications and certain fruits =7 days prior to starting study drug. Herbal medications include, but are not limited to St. John's wort, Kava, ephedra (ma huang), gingko biloba, dehydroepiandrosterone (DHEA), yohimbe, saw palmetto, and ginseng. Fruits include the CYP3A inhibitors Seville oranges, grapefruit, pummelos, or exotic citrus fruits.

20. Patients currently receiving treatment with therapeutic doses of warfarin sodium. Patients receiving low molecular weight heparin are allowed.

21. A serious active infection at the time of treatment, or another serious underlying medical condition that would impair the ability of the patient to receive protocol treatment.

22. Known diagnosis of human immunodeficiency virus (HIV), Hepatitis B (HBV) or Hepatitis C (HCV).

23. Presence of other active cancers, or history of treatment for invasive cancer =5 years. Patients with stage I cancer who have received definitive local treatment at least 3 years previously, and are considered unlikely to recur are eligible. All patients with previously treated in situ carcinoma (i.e. non-invasive) are eligible, as are patients with history of non-melanoma skin cancer.

24. Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.

25. Inability or unwillingness to comply with study and/or follow-up procedures outlined in the protocol.

26. Fertile male patients, defined as all males physiologically capable of conceiving offspring must use a highly effective contraception during dosing any study agent + [5 x T1/2] +12 weeks = contraception through 16 weeks after final dosing of study therapy and should not father a child during this period. In addition, female partners of male patients must use a highly effective contraception during dosing of any study agent + [5 x T1/2] +12 weeks = contraception through 16 weeks after the final dose of study therapy.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment


Related Conditions & MeSH terms


Intervention

Drug:
BKM 120

Cabazitaxel


Locations

Country Name City State
United States Florida Cancer Specialists-South Ft. Myers Florida
United States Tennessee Oncology PLLC Nashville Tennessee
United States Nebraska Methodist Hospital Omaha Nebraska

Sponsors (2)

Lead Sponsor Collaborator
SCRI Development Innovations, LLC Novartis

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Number of Subjects with Serious and Non-Serious Adverse Events Determine the optimal dose and safety of BKM120 given with cabazitaxel to patients with metastatic castrate-resistant prostate cancer. up to 24 months Yes
Primary Progression Free Survival (PFS) time to disease progression every 6 weeks, up to 24 months No
Secondary Overall Response Rate Percentage of complete responders (CR) or partial responders (PR) among patients evaluable for response every 6 weeks, up to 24 months No
Secondary Overall Survival Time from first treatment until death from any cause using Kaplan-Meier methods. up to 36 months No
See also
  Status Clinical Trial Phase
Not yet recruiting NCT06006104 - Phase 1/2 Clinical Study of HRS-4357 in Patients With Advanced Prostate Cancer Phase 1/Phase 2
Recruiting NCT03936218 - Goserelin 10.8mg Injection in Treatment of Advanced Prostate Cancer Phase 3
Completed NCT02234089 - Therapy Pathways in the Treatment of Hormone Naïve Prostate Cancer Patients With and Without Comorbidities Treated With Degarelix or Luteinizing-Hormone-Releasing-Hormone (LHRH) Agonists.
Completed NCT01078545 - Lucrin® Depot Efficacy and Safety Monitoring Study in Patients With Advanced Prostate Cancer and Lower Urinary Tract Symptoms (LUTS) N/A
Active, not recruiting NCT03511196 - Intermittent Androgen Deprivation Therapy for Stage IV Castration Sensitive Prostate Cancer Early Phase 1
Recruiting NCT05942001 - Study of HRS-5041 in Patients With Metastatic Castration Resistant Prostate Cancer (mCRPC) Phase 1
Active, not recruiting NCT04117594 - Whole Body Magnetic Resonance Imaging Study
Not yet recruiting NCT06369246 - PRORAD-5 PROstate RADiation in 5 Fractions: Phase Ib Five Fraction Radiotherapy for Patients With Advanced Prostate Cancer Phase 2
Completed NCT01383863 - A Long-term Observational Study Cohort in Patients With Advanced Prostate Cancer
Completed NCT03651271 - Nivolumab With or Without Ipilimumab in Advanced Metastatic Cancer Phase 2
Active, not recruiting NCT05590793 - Effects of Triptorelin Pamoate 6-month When Given to Adult Chinese Participants With Advanced Cancer in the Prostate Phase 3
Recruiting NCT06095089 - A Study of JNJ-87189401 Plus JNJ-78278343 for Advanced Prostate Cancer Phase 1
Active, not recruiting NCT02362620 - PROSTAC: Prospective Multi-centre Study of Prognostic Factors in mCRPC Patients Treated With Docetaxel or Cabazitaxel.
Active, not recruiting NCT02787837 - PROSABI: Prospective Multi-centre Study of Prognostic Factors in mCRPC Patients Treated With Abiraterone Acetate.
Recruiting NCT05800665 - A Study Evaluating the Safety, Pharmacokinetics, and Activity of RO7656594 In Participants With Advanced or Metastatic Prostate Cancer Phase 1
Recruiting NCT03938649 - SRAM study_Postate Cancer Phase 2
Completed NCT00871585 - Evaluation of Prostate-Specific Antigen (PSA) Levels in Patients With Advanced Prostate Cancer Treated With Bicalutamide N/A
Active, not recruiting NCT02922218 - PROSENZA: Prospective Multi-Centre Study of Prognostic Factors in mCRPC Patients Treated With Enzalutamide.
Not yet recruiting NCT06335914 - Dual PSMA and FDG PET Imaging for Patients With Advanced Prostate Cancer N/A
Terminated NCT03577028 - Study of HPN424 in Patients With Advanced Prostate Cancer Phase 1/Phase 2