Phase II, Randomized Study of MK-2206 and Bicalutamide (a type of hormonal therapy) v Bicalutamide alone in Patients With Rising Prostate-Specific Antigen (PSA) at High-Risk of Progression After Primary Therapy
- Conditions
- Patients with Rising PSA at high risk of Prostate cancer progressionMedDRA version: 17.1Level: PTClassification code 10071119Term: Hormone-dependent prostate cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2011-003847-22-IE
- Lead Sponsor
- ICORG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Male
- Target Recruitment
- 104
1.Patient must be at least 18 years of age.
2.Patient must have histologically confirmed diagnosis of prostate cancer.
3.Patient must have had previous treatment with definitive surgery or radiation therapy or cryoablation.
4.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.
5.Patient must have no evidence of metastatic disease on physical exam, CT abdomen/pelvis (or MRI), chest x-ray (or CT chest) and bone scan within 8 weeks prior to randomization.
6.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 PSADT were documented after the testosterone level was > 150 ng/dL.
7.Patient may not have had therapy modulating testosterone levels (such as luteinizinghormone, 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, MDV31000 megestrol acetate, 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.
8.Patient must have hormone-sensitive prostate cancer as evident by a serum total testosterone level > 150 ng/dL within 12 weeks prior to randomization.
9.Patient must have evidence of biochemical failure after primary therapy and subsequent progression.
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 RTGO-ASTRO Consensus definition).
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.
10. 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 50ng/mL and equal or higher than PSA3. PSA3 may be used as baseline PSA if obtained within 1 week of randomization.
11.Patient's PSA doubling time (PSADT) mus
14.HIV-positive patients are excluded from this study because of possible pharmacokinetic interactions with MK-2206.
15.Patient cannot receive concurrent therapeutic administration of anticoagulant therapy. Low dosage aspirin = 325 mg per day is allowed
16.Patients with impaired cardiac function including any one of the following will be excluded from entry on study:
oBaseline 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). A list of medications that may cause QTc interval prolongation are listed in Appendix VII, and should be avoided by patients entering on trial.
oPatients with congenital long QT syndrome
oHistory of sustained ventricular tachycardia
oAny history of ventricular fibrillation or torsades de pointes
oConcomitant use of drugs with a risk of causing torsades de pointes
oBracardia defined as heart rate < 50 beats per minute. Patients with a pacemaker and heart rate = 50 beats per minute are eligible.
oMyocardial infarction or unstable angina within 6 months of study entry
oCongestive heart failure (NY Heart Association class III or IV)
oRight bundle branch block and left anterior hemi-block (bifasicular block)
17.Patient must not have GI tract disease resulting in an inability to take oral medication, malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn’s, ulcerative colitis).
18.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.
19.Patient may not have a history of allergic reactions attributed to compounds of similar chemical or biologic composition to MK-2206 or bicalutamide.
20.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.
21.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. Please follow Section 5.4.4 for glucose monitoring during study for this patient population.
22.Patients receiving any medications or substances that are inhibitors or inducers of CYP 450 3A4 are ineligible. Lists including medications and substances known or with the potential to interact with the CYP 450 3A4 isoenzymes are provided in Appendix VI.
23.Patient must NOT have other current malignancies. 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.
24.The effect of the study medications on the developing human fetus are unknown. For this reason, 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 immediately.
25.Patients must discontinue use of enzyme-inducing anti-epileptic drugs (EIAEDs) =14 days
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method