Bicalutamide With or Without Akt Inhibitor MK2206 in Treating Patients With Previously Treated Prostate Cancer

Not Recruiting

Trial ID: NCT01251861


This phase II trial studies how well giving bicalutamide with or without Akt inhibitor MK2206 works in treating patients with previously treated prostate cancer. Androgens can cause the growth of prostate cancer cells. Antihormone therapy, such as bicalutamide, may lessen the amount of androgens made by the body. Akt inhibitor MK2206 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether bicalutamide is more effective with or without Akt inhibitor MK2206 in treating prostate cancer.

Official Title

Androgen Receptor Modulation Phase II, Randomized Study of MK-2206 - Bicalutamide Combination in Patients With Rising PSA at High-Risk of Progression After Primary Therapy

Stanford Investigator(s)

Harlan Pinto
Harlan Pinto

Associate Professor of Medicine (Oncology) and of Otolaryngology - Head & Neck Surgery

Sandy Srinivas
Sandy Srinivas

Professor of Medicine (Oncology) and, by courtesy, of Urology


Inclusion Criteria:

   - Patient must have histologically confirmed diagnosis of prostate cancer

   - Patient must have had previous treatment with definitive surgery or radiation therapy
   or cryoablation

   - Patient may have prior salvage therapy (surgery, radiation or other local ablative
   procedures) within 4 weeks prior to randomization if the intent was for cure;
   prophylactic radiotherapy to prevent gynecomastia within 4 weeks prior to
   randomization is allowed

   - Patient must have no evidence of metastatic disease on physical exam, computed
   tomography (CT) abdomen/pelvis (or magnetic resonance imaging [MRI]), chest x-ray (or
   CT chest) and bone scan within 8 weeks prior to randomization

   - Patient may have had prior neoadjuvant and/or adjuvant therapy (chemotherapy, vaccines
   or experimental agents) within 4 weeks prior to randomization, if the PSA rise and PSA
   doubling time (PSADT) were documented after the testosterone level was > 150 ng/dL

   - Patient may not have had therapy modulating testosterone levels (such as
   luteinizing-hormone, releasing-hormone agonists/antagonists and antiandrogens) within
   1 year prior to randomization, unless it was in the neoadjuvant and/or adjuvant
   setting; agents such as 5 alpha reductase inhibitors, ketoconazole, abiraterone,
   systemic steroids, or herbal supplements known to decrease PSA levels including any
   dose of megestrol acetate, finasteride (e.g., Saw Palmetto and PC-SPES, African pygeum
   extract, lycopene, alanine, glutamic acid and glycine, beta-sitosterol, lycopene,
   nettle root extract, quercitin, Belizian Man Vine extract, mulra puama extract and
   epimedium extract campesterol, beta-sitosterol, stigmasterol, sitostanol and
   brassicasterol) are not permitted at any time during the period that the PSA values
   are being collected

   - Patient must have hormone-sensitive prostate cancer as evident by a serum total
   testosterone level > 150 ng/dL within 12 weeks prior to randomization

   - Patient must have evidence of biochemical failure after primary therapy and subsequent

      - Biochemical failure is declared when the PSA reaches a threshold value after
      primary treatment and it differs for radical prostatectomy or radiation therapy

      - For radical prostatectomy the threshold for this study is PSA >= 0.4 ng/mL

      - For radiation therapy the threshold is a PSA rise of 2 ng/mL above the nadir PSA
      achieved post radiation with or without hormone therapy (2006 Radiation Therapy
      Oncology Group [RTOG]-American Society for Radiation Oncology [ASTRO] Consensus

      - PSA progression requires a PSA rise above the threshold (PSA1) measured at any
      time point since the threshold was reached

      - The PSADT must be < 12 months; requires two consecutive PSA rises (PSA2 and PSA3)
      above the PSA1; PSA2 and PSA3 must be obtained within 6 months of study entry;
      all baseline PSAs should be obtained, preferably, at the same reference lab

   - PSADT calculation needs 3 PSA values:

      - PSA1 is any PSA value that is equal or greater than the threshold PSA (0.4 ng/mL
      for radical prostatectomy or 2 ng/mL above the nadir for primary radiation
      therapy) indicating biochemical relapse

      - PSA2 must be higher than PSA1, obtained at least 2 weeks after PSA1 and within 6
      months or less from randomization

      - PSA3 must be higher than PSA2 and obtained at least 2 weeks after PSA2

      - Baseline PSA must have reached a minimum of 2 ng/mL but be no greater than 50
      ng/mL and equal or higher than PSA3; PSA3 may be used as baseline PSA if obtained
      within 1 week of randomization

   - Patient's PSA doubling time (PSADT) must be less than 12 months

   - Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0
   or 1

   - Granulocytes >= 1,500/mm^3

   - Platelet count >= 100,000/mm^3

   - Serum creatinine within normal institutional limits or creatinine clearance >= 50
   ml/min for patients with creatinine levels above institutional normal

   - Serum total bilirubin =< 1.5 times upper limit of normal (ULN)

   - Alkaline phosphatase (ALP) =< 2.5 x ULN

   - Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and
   serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 2.5 x
   institutional upper limit of normal

   - Human immunodeficiency virus (HIV)-positive patients are excluded from this study

   - Patient cannot receive concurrent therapeutic administration of anticoagulant therapy;
   low dosage aspirin =< 325 mg per day is allowed

   - Patients with impaired cardiac function including any one of the following will be
   excluded from entry on study:

      - Baseline corrected QT interval (QTc) > 450 msec (male) (patients with QTc 450-480
      msec will be allowed to participate in this trial if they do not have any of the
      other cardiac conditions mentioned in this section)

      - Patients with congenital long QT syndrome

      - History of sustained ventricular tachycardia

      - Any history of ventricular fibrillation or torsades de pointes

      - Concomitant use of drugs with a risk of causing torsades de pointes

      - Bradycardia defined as heart rate < 50 beats per minute; patients with a
      pacemaker and heart rate >= 50 beats per minute are eligible

      - Myocardial infarction or unstable angina within 6 months of study entry

      - Congestive heart failure (New York Heart Association class III or IV)

      - Right bundle branch block and left anterior hemi-block (bifascicular block)

   - Patient must not have gastrointestinal (GI) tract disease resulting in an inability to
   take oral medication, malabsorption syndrome, a requirement for intravenous (IV)
   alimentation, prior surgical procedures affecting absorption, uncontrolled
   inflammatory GI disease (e.g., Crohn's, ulcerative colitis)

   - Patient may not be receiving any other investigational agents or receiving concurrent
   anticancer therapy (chemotherapy, immunotherapy, radiation therapy, surgery for
   cancer, or experimental medications) at time of randomization

   - Patient may not have a history of allergic reactions attributed to compounds of
   similar chemical or biologic composition to MK-2206 or bicalutamide

   - Patient must not have any uncontrolled intercurrent illness including, but not limited
   to, ongoing or active infection, cardiac arrhythmia, or psychiatric illness/social
   situations that would limit compliance with study requirements

   - Patients with diabetes or at risk for hyperglycemia MUST not be excluded from trials
   with MK-2206, but the hyperglycemia should be well controlled before the patient
   enters the trial

   - Patients receiving any medications or substances that are inhibitors or inducers of
   cytochrome P450, family 3, subfamily A, polypeptide 4 (CYP3A4) are ineligible

   - Patient must NOT have previous or concurrent malignancy; exceptions are made for
   patients who meet any of the following conditions:

      - Basal cell or squamous cell carcinoma of the skin OR

      - Prior malignancy has been adequately treated and patient has been continuously
      disease free for >= 2 years

   - Patient must agree to use barrier contraception during and for 3 months after
   discontinuation of study treatment; if patient impregnates a woman while on treatment
   or within 3 months of discontinuing treatment, he should inform his treating physician

   - Patients must discontinue use of enzyme-inducing anti-epileptic drugs (EIAEDs) >= 14
   days prior to study enrollment; the investigator may prescribe non-EIAEDs; patients
   who must begin EIAED therapy while on study will be allowed to remain

   - Patients must not be taking cytochrome P450 enzyme-inducing antiepileptic drugs
   (phenytoin, carbamazepine or phenobarbital), St John's Wort, ketoconazole,
   dexamethasone, the dysrhythmic drugs (terfenadine, quinidine, procainamide, sotalol,
   probucol, bepridil, indapamide or flecainide), haloperidol, risperidone, rifampin,
   grapefruit, or grapefruit juice within two weeks of randomization and during the
   course of therapy

   - Patients may have received targeted agents (angiogenesis inhibitors, epidermal growth
   factor receptor [EGFR] inhibitors, mammalian target of rapamycin [mTOR] inhibitors,
   phosphatidylinositol 3 kinase [PI3K] inhibitors, etc.), however patients must have
   discontinued treatment with the targeted agent(s) at least 4 weeks prior to
   enrollment; if the patient stopped targeted agent(s) due to unresolved or persistent
   grade 3 or 4 toxicity, patient cannot be enrolled onto the study regardless of the
   length of time since discontinuation of treatment with targeted agent(s)


drug: Akt inhibitor MK2206

drug: bicalutamide

other: Clinical Observation

other: Laboratory Biomarker Analysis

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Cancer Clinical Trials Office

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