A Multicenter Phase I/II Trial of Abiraterone Acetate + BEZ235 in Metastatic, Castration-Resistant Prostate Cancer

Stopped early · Phase 1/Phase 2

Conditions studied: Castrate-resistant Prostate Cancer

In brief

There will be two parts to this clinical research study. The purpose of each part is: * Phase 1: This part of the study will determine what dose of BEZ235 is safe to give with a standard dose of abiraterone acetate and prednisone by administering different doses of BEZ235. This will help to find out what effects, good and/or bad, this combination has on CRPC. * Phase 2: This part of the study will measure the treatment effect of the combination of BEZ235 and abiraterone acetate/prednisone on CRPC.

Key facts

Study ID

NCT01717898

Run by

Charles Ryan

People needed

6

Starts

2013-01-31

Expected to finish

2016-08-29

Last updated by the study team

2018-03-27

Who can join

Age: 18 and older. Sex: male. Healthy volunteers: not accepted.

You may qualify if…

• Patients eligible for inclusion in this study have to meet all of the following criteria:
• Patient has provided a signed study Informed Consent Form prior to any screening procedure.
• Patient is ≥ 18 years of age on the day of consenting to the study.
• Patients must have histologically confirmed adenocarcinoma of the prostate.
• Radiographic evidence of disease (bone scan, CT scan, ultrasound or MRI acceptable) that is amenable to image-guided biopsy must be present.
• Patients must have castrate levels of testosterone (< 50 ng/dL) on GnRH analogues or have had prior orchiectomy. GnRH analogues must be continued while on study.
• Progressive disease as demonstrated by a rising PSA or radiographic progression per PCWG2 criteria.
• Asymptomatic or minimally symptomatic disease: No use of opiate analgesics (EXCLUDING codeine or dextromethorphan) for cancer related pain within 28 days of day 1, cycle 1.
• Phase II Cohort 1: No prior Abiraterone Acetate therapy
• Phase II Cohort 2: Immediate prior Abiraterone Acetate therapy is required. No intervening therapy is allowed between Abiraterone Acetate therapy and study therapy.
• Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• Men of reproductive potential who have not had a radical prostatectomy must agree to use an effective contraceptive method. Patients who have had a prostatectomy are sterile and do not need to use contraception.
• Patient has adequate bone marrow and organ function as shown by:
• Absolute neutrophil count (ANC) ≥ 1.0 x 109/L
• Platelets ≥ 100 x 109/L
• Hemoglobin (Hgb) ≥ 9.0 g/dL
• INR ≤ 2
• Serum creatinine ≤ 1.5 x ULN
• Total serum bilirubin ≤ 1.5 x ULN (in patients with known Gilbert Syndrome, a total bilirubin ≤ 3.0 x ULN, with direct bilirubin ≤ 1.5 x ULN)
• AST and ALT ≤ 3 x ULN (or ≤ 5.0 x ULN if hepatic metastases are present)
• Fasting plasma glucose (FPG) ≤ 140mg/dL [7.8 mmol/L]
• HgbA1c ≤8% (Patients with diabetes mellitus not actively being treated and patients with an HgbA1c level between 7-8% will be required to have home glucose monitoring three times weekly during the first cycle. Patients may also be referred to a diabetes specialist as indicated.)

You may not qualify if…

• Patients eligible for this study must not meet any of the following criteria:
• Patient has received previous treatment with PI3K and/or mTOR inhibitors.
• Phase II Cohort 1: Prior Abiraterone Acetate therapy is an exclusion
• Prior therapy with any of the following for >1 month: MDV-3100, Orteronel, ketoconazole or other drugs given with the intention to inhibit CYP 17.
• Patient has active uncontrolled or symptomatic CNS metastases. Note: A patient with controlled and asymptomatic CNS metastases may participate in this trial. As such, the patient must have completed any prior treatment for CNS metastases > 90 days (including radiotherapy and/or surgery) prior to start of treatment in this study and should not be receiving chronic corticosteroid therapy for the CNS metastases.
• Patient has a concurrent malignancy or has had a malignancy in the last 3 years prior to start of study treatment (with the exception of adequately treated basal or squamous cell carcinoma or cervical carcinoma in situ).
• Patient has received wide field radiotherapy (including therapeutic radioisotopes such as strontium 89) ≤ 28 days or limited field radiation for palliation ≤ 14 days prior to starting study drug or has not recovered from side effects of such therapy.
• 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 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)
• QTcF > 480 msec on screening ECG
• Unstable angina pectoris
• 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
• Family history of congenital long or short QT, or known history of QT/QTc prolongation or Torsades de Pointes (TdP).
• Patient with medically documented history of active major depressive episodes, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation.
• Active or uncontrolled infection of hepatitis B or hepatitis C.
• Inadequately controlled hypertension (i.e., SBP > 180 mmHg or DBP > 100 mmHg).

Where it is running

• University of California, San Francisco — San Francisco, California, United States

Full record on ClinicalTrials.gov

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