Olaparib + Chemotherapy for Prostate Cancer

Recruiting in Palo Alto (17 mi)

+1 other location

Age: 18+

Sex: Male

Travel: May be covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: M.D. Anderson Cancer Center

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?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.

Eligibility Criteria

This trial is for men over 18 with aggressive variant prostate cancer (AVPC) that's resistant to castration and has spread. They must have normal organ function, be able to swallow pills, consent to genetic research, and use birth control if needed. Excluded are those with certain medical conditions or who've had specific treatments for CRPC.

Inclusion Criteria

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 serum carcinoembryonic 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

Patients must have normal organ and bone marrow function measured within 7 days prior to administration of study treatment as defined below: i. Hemoglobin >/= 10.0 g/dL dL (unless due to bone marrow infiltration by tumor, in which case hemoglobin >/=8gdL is allowed). Patient may have blood transfusions prior to study enrollment. ii. Absolute neutrophil count (ANC) >/= 1.5 x 10^9/L (unless due to bone marrow infiltration by tumor, in which case ANC >1,000/mm3 is allowed) iii. White blood cells (WBC) >3x10^9/L (unless due to bone marrow infiltration by tumor, in which case WBC >2x109/L is allowed) iv. No features suggestive of myelodysplastic syndrome/acute myeloid leukemia on peripheral blood smear v. Platelet count >/= 100 x 10^9/L (unless due to bone marrow infiltration by tumor, in which case platelet >/=50,000/ mm3 is allowed) vi. Total bilirubin </=1.5 x institutional upper limit of normal (ULN) (except for patients with known Gilbert's disease) vii. aspartate aminotransferase (serum glutamine oxaloacetic transminase) and alanine aminotransferase (serum glutamic pyruvic transaminase) </= 2.5 x institutional upper limit of normal (unless liver metastases are present in which case it must be </= 5x ULN) viii. Calculated creatinine clearance (Cockcroft-Gault Equation) >/= 40 mL/min

I am a man aged 18 or older.

My prostate cancer diagnosis was confirmed through lab tests.

I can perform daily activities with minimal assistance.

My cancer is getting worse, shown by tests or new symptoms.

My prostate cancer is resistant to hormone therapy and is worsening, but my PSA levels are not rising.

I can swallow pills whole.

I am undergoing treatment to lower my testosterone levels below 50 ng/dL.

Exclusion Criteria

I have been treated for prostate cancer with specific drugs.

I am allergic to olaparib, carboplatin, or cabazitaxel.

I cannot swallow pills or have stomach issues affecting medication absorption.

I have recovered from side effects of cancer treatment, except for specific prostate cancer therapies.

I am not currently using strong or moderate drugs that affect liver enzymes.

I am diagnosed or suspected to have a blood disorder or leukemia.

I have active hepatitis or chronic liver disease.

I have had lung inflammation or widespread lung disease not caused by cancer.

Participant Groups

The study tests if olaparib can control AVPC after treatment with cabazitaxel, carboplatin, and prednisone. It's an investigational study of these drugs' combination; up to 96 participants at MD Anderson will receive this regimen following informed consent.

3Treatment groups

Experimental Treatment

Active Control

Group I: Olaparib MaintenanceExperimental Treatment1 Intervention

Participants randomized to receive Olaparib by mouth twice daily on Day 1 of cycle 7.

Group II: Cabazitaxel + CarboplatinExperimental Treatment3 Interventions

Cabazitaxel, Cabazitaxel and Carboplatin intravenously on day 1 of cycles 1-6. Prednisone by mouth twice daily on days 1-21 of cycles 1-6.

Group III: Observation OnlyActive Control1 Intervention

Participants randomized to observation only beginning cycle 7.

Cabazitaxel is already approved in European Union, United States, Canada, Japan for the following indications:

🇪🇺 Approved in European Union as Jevtana for: