Study of Olaparib Maintenance Following Cabazitaxel-Carbo in Men With AVPC (NCT03263650) | Clinical Trial Compass
Active — Not RecruitingPhase 2
Study of Olaparib Maintenance Following Cabazitaxel-Carbo in Men With AVPC
United States96 participantsStarted 2017-10-03
Plain-language summary
The goal of this clinical research study is to learn if olaparib, when given after treatment with cabazitaxel, carboplatin, and prednisone, can help to control aggressive variant prostate cancer (AVPC). The safety of these drugs will also be studied.
This is an investigational study. Cabazitaxel and carboplatin are FDA approved and commercially available for the treatment of certain types of prostate cancer. Prednisone is FDA-approved and commercially available as a corticosteroid. Olaparib is FDA approved and commercially available for the treatment of certain types of ovarian cancer. The combination of cabazitaxel and carboplatin followed by olaparib in this study is investigational.
The study doctor can describe how the study drugs are designed to work.
Up to 96 participants will be enrolled on this study. All will take part at MD Anderson.
Who can participate
Age range18 Years
SexMALE
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion criteria
✓. Provision of informed consent prior to any study specific procedures.
✓. Provision of informed consent for genetic research. If a patient declines to participate in the genetic research, there will be no penalty or loss of benefit to the patient. The patient will not be excluded from other aspects of the study described in this Clinical Study Protocol, so long as they consent to that part.
✓. Patients must agree to tissue collection for correlative studies at the specified timepoints. If patient has undergone a recent tissue collection without intervening treatment since, that can be retrieved and is deemed of sufficient quantity by the PI to undertake the proposed correlative studies, it may be used as the baseline.
✓. Male aged 18 years and above.
✓. Histologically or cytologically confirmed prostate carcinoma.
✓. Presence of metastatic disease documented on imaging studies (bone scan, computed tomography (CT) and/or magnetic resonance imaging (MRI) scans).
✓. Patients must meet at least one of the following AVPC criteria: i. Histologically proven small cell (neuroendocrine) prostate carcinoma ii. Exclusive visceral metastases. iii. Predominantly lytic bone metastases identified by plain x-ray or CT scan. iv. Bulky (\>/= 5cm in longest dimension) lymphadenopathy or high-grade tumor mass in prostate/pelvis. v. Low PSA (\</= 10ng/mL) at initial presentation (prior to androgen ablation or at symptomatic progression in the castrate-setting) plus high volume (\>/= 20) bone metastases. vi. Elevated serum lactate dehydrogenase (\>/=2 x upper limit of normal) or elevated serumcarcinoembryonic antigen (\>/= 2 x upper limit of normal ) in the absence of other etiologies. vii. Short interval (\</= 180 days) to castrate-resistant progression following initiation of hormonal therapy. viii. Known loss or mutation (by CLIIA certified molecular testing, IHC and/or DNA sequencing) in at least 2 of the following: Tp53, RB1 and PTEN.
What they're measuring
1
Progression-free survival (PFS) of men with AVPC treated with 6 cycles of cabazitaxel + carboplatin followed by olaparib maintenance versus observation
Timeframe: Up to one year from time of randomization
✓. (continued from Inclusion Criteria #7: viiii. Patients who have castration -resistant disease progression per RECIST but do not meet PCWG3 PSA progression criteria
Exclusion criteria
✕. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at MD Anderson)
✕. Previous enrolment or randomization in the present study
✕. Any prior treatment for castration-resistant prostate cancer (CRPC) with carboplatin, cisplatin, cabazitaxel or olaparib.
✕. Patients whose disease is refractory (defined as evidence of disease progression while on drug or within 3 months of its discontinuation) to more than 2 lines of chemotherapy given for CRPC. Any number of chemotherapies to which the patient's disease is not refractory are allowed, as long as time on treatment did not exceed 6 months (counted from day 1 of cycle 1 to day 1 of the last cycle of treatment).
✕. Patients who have not recovered from adverse events secondary to systemic therapy (except for luteinizing hormone-releasing (LHRH) hormone agonist or antagonist treatment for prostate cancer, and bisphosphonates or receptor activator of Nf kappa (RANK) ligand inhibitors for bone strengthening), major surgery or radiotherapy for the treatment of prostate cancer to a grade \</= 2.
✕. Persistent toxicities (\>/= common terminology criteria for adverse events grade 2) with the exception of alopecia, caused by previous cancer therapy.
✕. Chronic use of known strong CYP3A4 inhibitors (e.g. ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, telithromycin, clarithromycin, voriconazole, nefazodone, posaconazole, ritonavir, lopinavir/ritonavir, indinavir, saquinavir, boceprevir, telaprevir and nelfinavir), moderate CYP3A4 inhibitors (e.g. amprenavir, aprepitant, atazanavir, ciprofloxacin, crizotinib, darunavir/ritonavir, diltiazem, erythromycin, fluconazole, fosamprenavir, imatinib, verapamil), strong CYP3A4 inducers (e.g. phenytoin, rifampicin, carbamazepine, St.John's Wort, phenobarbital) and moderate CYP3A4 inducers (e.g. bosentan, efavirenz, etravirine, modafinil and nafcillin). Concomitant use of these drugs with olaparib is not allowed. Patients may undergo limited courses of them prior to starting olaparib but will be required to have \>/= 5 week washout period from phenobarbital, and \>/=3 week washout period from the rest, before randomization.
✕. Active uncontrolled infection ( patients completing a course of antibiotic or antiviral therapy whose infection is deemed to be controlled may be allowed on study after discussion with the PI; the PI will serve as the final arbiter regarding eligibility).