Phase I/II Study of PEGylated Arginine Deiminase (ADI-PEG20) With Carboplatin and Cabazitaxel in Men With Aggressive Variant Prostate Cancers (AVPC)
- Conditions
- Prostate Cancer
- Registration Number
- NCT06085729
- Lead Sponsor
- M.D. Anderson Cancer Center
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Male
- Target Recruitment
- Not specified
Inclusion Criteria:<br><br> 1. Completion of informed consent prior to any study specific procedures.<br><br> 2. Patients must agree to tissue collection for correlative studies at the specified<br> timepoints.<br><br> 3. Patients must consent to the MD Anderson Immunotherapy Platform laboratory protocol<br> PA13-0291.<br><br> 4. Male aged 18 years and above.<br><br> 5. Histologically or cytologically confirmed prostate carcinoma.<br><br> 6. Presence of metastatic disease documented on imaging studies (bone scan, CT and/or<br> MRI scans).<br><br> 7. Patients must meet at least one of the following AVPC criteria:<br><br> i. Histologically proven small cell (neuroendocrine) prostate carcinoma ii.<br> Exclusive visceral metastases. iii. Predominantly lytic bone metastases identified<br> by plain x-ray or CT scan. iv. Bulky (=5cm in longest dimension) lymphadenopathy or<br> high-grade tumor mass in prostate/pelvis. v. Low PSA (= 10ng/mL) at initial<br> presentation (prior to androgen ablation or at symptomatic progression in the<br> castrate-setting) plus high volume (= 20) bone metastases. vi. Elevated serum LDH<br> (=2 x ULN) or elevated serum CEA (=2 x ULN) in the absence of other etiologies. vii.<br> Short interval (=180 days) to castrate-resistant progression following initiation of<br> hormonal therapy. viii. Known loss or mutation (by CLIA certified molecular testing,<br> IHC and/or DNA sequencing) in at least 2 of Tp53, RB1 and PTEN defined as:<br><br> - AVPC determination by immunohistochemistry. Tumor samples are considered<br> negative (and thus abnormal) for RB1 and PTEN if their labeling index is = 10%<br> and positive (and thus aberrant) for Tp53 if their labeling index is = 10%,<br> where the labeling index is defined as the percentage of positive cells, and<br> calculated as the number of positively stained epithelial cells divided by the<br> total number of epithelial cells, at X200 magnification.<br><br> - AVPC determination by DNA sequencing. The TP53, RB1 and PTEN genes will be<br> considered aberrant if they contain exonic nonsynonymous missense or stop-gain<br> mutations, frameshift or non-frameshift indels (insertions or deletions),<br> and/or copy number losses.<br><br> ix. Patients who have castration-resistant disease progression per RECIST in the<br> absence of PSA values rising to = 1.0ng/mL as per PCGW3 PSA progression criteria<br><br> 8. Patients must have documented evidence of progressive disease as defined by any of<br> the following:<br><br> I. PSA progression: minimum of 2 rising values (3 measurements) obtained a minimum<br> of 7 days apart with the last result being at least = 1.0 ng/mL; II. New or<br> increasing non-bone disease (RECIST); III. Positive bone scan with 2 or more new<br> lesions (PCWG3); IV. Increasing symptoms unequivocally attributed to disease<br> progression as judged by the treating physician and the PI; V. Biopsy proven new<br> transformation to small cell carcinoma in a patient previously diagnosed with an<br> adenocarcinoma of the prostate.<br><br> 9. Surgically or ongoing medically castrated, with baseline testosterone levels of = 50<br> ng/dL (=2.0 nM).<br><br> Exception: Patients with de novo primary small cell carcinoma of the prostate may<br> begin chemotherapy on study once treatment with an LHRH agonist or antagonist has<br> been initiated, even if testosterone levels have not reached = 50ng/dL.<br><br> 10. Eastern Cooperative Oncology Group (ECOG) Performance Status of =2.<br><br> 11. Patients must have adequate organ and bone marrow function measured within 7 days<br> prior to treatment registration as defined below:<br><br> I. Hemoglobin = 9.0 g/dL (unless deemed by the treating physician to be due to bone<br> marrow infiltration by tumor, in which case hemoglobin =8gdL is allowed). Patient<br> may have blood transfusions prior to study enrollment. II. Absolute neutrophil count<br> (ANC) =1.5 x 109/L (unless deemed by the treating physician to be due to bone marrow<br> infiltration by tumor, in which case ANC =1,000/mm3 is allowed) III. White blood<br> cells (WBC) =3x109/L (unless deemed by the treating physician to be due to bone<br> marrow infiltration by tumor, in which case WBC =2x109/L is allowed) IV. Platelet<br> count = 100 x 109/L (unless deemed by the treating physician to be due to bone<br> marrow infiltration by tumor, in which case platelet =75,000/ mm3 is allowed) V.<br> Total bilirubin = 1.5 x institutional upper limit of normal (ULN) (except for<br> patients with known Gilbert's disease). VI. AST (SGOT) and ALT (SGPT) = 2.5 x<br> institutional upper limit of normal (unless liver metastases are present, in which<br> case it must be = 5x ULN) VII. Calculated creatinine clearance (Cockcroft-Gault<br> Equation) = 30 mL/min.<br><br> 12. Patients who have partners of childbearing potential (e.g., female that has not been<br> surgically sterilized or who are not amenorrheic for = 12 months) must be willing to<br> use a method of birth control in addition to adequate barrier protection as<br> determined to be acceptable by the investigator during the study and for 3 months<br> after last dose of ADI-PEG 20 administration. In addition, men should not donate<br> sperm during this period.<br><br> 13. Patient is willing and able to comply with the protocol for the duration of the<br> study including undergoing treatment and scheduled visits and examinations including<br> follow up.<br><br>Exclusion Criteria:<br><br> 1. Any prior treatment for CRPC with carboplatin, cisplatin or cabazitaxel.<br><br> 2. Patients who have received more than one line of chemotherapy. Any number of prior<br> hormonal or targeted therapies are allowed.<br><br> 3. Patients who have not recovered from adverse events secondary to systemic therapy<br> (except for LHRH agonist or antagonist treatment for prostate cancer, and<br> bisphosphonates or RANK ligand inhibitors for bone strengthening), major surgery or<br> radiotherapy for the treatment of prostate cancer to a grade </= 2.<br><br> 4. Any unresolved toxicity (CTCAE Grade =2) from previous anti-cancer therapy. Subjects<br> with irreversible toxicity that is not reasonably expected to be exacerbated by the<br> investigational product may be included (e.g., hearing loss, peripherally<br> neuropathy).<br><br> 5. Active uncontrolled infection (patients completing a course of antibiotic or<br> antiviral therapy whose infection is deemed to be controlled may be allowed on study<br> after discussion with the PI; the PI will serve as the final arbiter regarding<br> eligibility).<br><br> 6. Active or symptomatic viral hepatitis or chronic liver disease.<br><br> 7. A history of pneumonitis or extensive bilateral lung disease of non-malignant<br> etiology.<br><br> 8. A malignancy [other than the one treated in this study] which has a '= 30%<br> probability of recurrence within 24 months (except for adequately treated<br> non-melanoma skin cancer, curatively treated in situ cancer of the cervix or Ta<br> urothelial carcinomas).<br><br> 9. Any underlying medical or psychiatric condition, which in the opinion of the<br> Investigator, will make the administration of study drug hazardous or obscure the<br> interpretation of adverse events. Examples: include, but are not limited to,<br> uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction,<br> superior vena cava syndrome, extensive bilateral lung disease on HRCT scan,<br> uncontrolled seizu
Not provided
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
- Secondary Outcome Measures
Name Time Method