Phase I/II Study of PEGylated Arginine Deiminase (ADI-PEG20) With Carboplatin and Cabazitaxel in Men With Aggressive Variant Prostate Cancers (AVPC)

NCT06085729 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 2023-0467NCI-2023-08684
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

To find the best dose of ADI-PEG20 that can be given in combination with carboplatin and cabazitaxel to patients with AVPC.

Conditions

Prostate Cancer

Outcome Measures

Primary Outcomes (1)

• Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

  Through study completion; an average of 1 year.

Study Arms (1)

Dose Escalation and Monotherapy Maintenance

EXPERIMENTAL

Participants will be assigned to a study group and dose level of ADI-PEG20 based on when participant join this study. Up to 2 dose levels of ADI-PEG20 may be tested. Up to 15 participants will be enrolled per dose level.

Drug: ADI-PEG 20; Drug: Cabazitaxel; Drug: Carboplatin

Interventions

Cabazitaxel DRUG

Given by IV (vein)

Also known as: Jevtana®

Dose Escalation and Monotherapy Maintenance

Carboplatin DRUG

Given by IV (vein)

Also known as: Paraplatin®

Dose Escalation and Monotherapy Maintenance

ADI-PEG 20 DRUG

Given by Injection

Dose Escalation and Monotherapy Maintenance

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Completion of informed consent prior to any study specific procedures.
• Patients must agree to tissue collection for correlative studies at the specified timepoints.
• Patients must consent to the MD Anderson Immunotherapy Platform laboratory protocol PA13-0291.
• Male aged 18 years and above.
• Histologically or cytologically confirmed prostate carcinoma.
• Presence of metastatic disease documented on imaging studies (bone scan, CT and/or 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 LDH (≥2 x ULN) or elevated serum CEA (≥2 x ULN) 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 CLIA certified molecular testing, IHC and/or DNA sequencing) in at least 2 of Tp53, RB1 and PTEN defined as:
• AVPC determination by immunohistochemistry. Tumor samples are considered negative (and thus abnormal) for RB1 and PTEN if their labeling index is ≤ 10% and positive (and thus aberrant) for Tp53 if their labeling index is ≥ 10%, where the labeling index is defined as the percentage of positive cells, and calculated as the number of positively stained epithelial cells divided by the total number of epithelial cells, at X200 magnification.
• AVPC determination by DNA sequencing. The TP53, RB1 and PTEN genes will be considered aberrant if they contain exonic nonsynonymous missense or stop-gain mutations, frameshift or non-frameshift indels (insertions or deletions), and/or copy number losses.
• ix. Patients who have castration-resistant disease progression per RECIST in the absence of PSA values rising to ≥ 1.0ng/mL as per PCGW3 PSA progression criteria
• Patients must have documented evidence of progressive disease as defined by any of the following:
• I. PSA progression: minimum of 2 rising values (3 measurements) obtained a minimum of 7 days apart with the last result being at least ≥ 1.0 ng/mL; II. New or increasing non-bone disease (RECIST); III. Positive bone scan with 2 or more new lesions (PCWG3); IV. Increasing symptoms unequivocally attributed to disease progression as judged by the treating physician and the PI; V. Biopsy proven new transformation to small cell carcinoma in a patient previously diagnosed with an adenocarcinoma of the prostate.
• Surgically or ongoing medically castrated, with baseline testosterone levels of ≤ 50 ng/dL (≤2.0 nM).
• Exception: Patients with de novo primary small cell carcinoma of the prostate may begin chemotherapy on study once treatment with an LHRH agonist or antagonist has been initiated, even if testosterone levels have not reached ≤ 50ng/dL.

You may not qualify if:

• Any prior treatment for CRPC with carboplatin, cisplatin or cabazitaxel.
• Patients who have received more than one line of chemotherapy for prostate cancer. Any number of prior hormonal or targeted therapies are allowed.
• Patients who have not recovered from adverse events secondary to systemic therapy (except for LHRH agonist or antagonist treatment for prostate cancer, and bisphosphonates or RANK ligand inhibitors for bone strengthening), major surgery or radiotherapy for the treatment of prostate cancer to a grade \</= 2.
• Any unresolved toxicity (CTCAE Grade ≥2) from previous anti-cancer therapy. Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational product may be included (e.g., hearing loss, peripherally neuropathy).
• 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).
• Active or symptomatic viral hepatitis or chronic liver disease.
• A history of extensive bilateral lung disease of non-malignant etiology.
• A malignancy \[other than the one treated in this study\] which has a '≥ 30% probability of recurrence within 24 months (except for adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix or Ta urothelial carcinomas).
• Any underlying medical or psychiatric condition, which in the opinion of the Investigator, will make the administration of study drug hazardous or obscure the interpretation of adverse events. Examples: include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, superior vena cava syndrome, extensive bilateral lung disease on HRCT scan, uncontrolled seizures, history of allogeneic organ transplant, history of primary immunodeficiency or any psychiatric disorder that prohibits obtaining informed consent.
• Patients with symptomatic uncontrolled brain metastases or spinal cord compressions. A scan to confirm the absence of brain metastases is not required.
• Prisoners or subjects who are involuntarily incarcerated.
• Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to ADI-PEG 20, pegylated compounds, or other agents used in this study.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

ADI PEG20; cabazitaxel; Carboplatin

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals

Study Officials

• Ana Aparicio, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ana Aparicio, MD

CONTACT

(713) 563-6969; aaparicio@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 10, 2023
• First Posted: October 17, 2023
• Study Start: February 29, 2024
• Primary Completion (Estimated): September 2, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: April 2, 2026

Record last verified: 2026-03

Locations

US (1)