Cabazitaxel, Carboplatin, and Cetrelimab Followed by Niraparib With or Without Cetrelimab for the Treatment of Aggressive Variant Metastatic Prostate Cancer

NCT04592237 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 2020-0200NCI-2020-07731
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies the effect of cabazitaxel, carboplatin, and cetrelimab followed by niraparib with or without cetrelimab in treating patients with aggressive variant prostate cancer that has spread to other places in the body (metastatic). Chemotherapy drugs, such as cabazitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. PARPs are proteins that help repair DNA mutations. PARP inhibitors, such as niraparib, can keep PARP from working, so tumor cells can't repair themselves, and they may stop growing. Immunotherapy with monoclonal antibodies, such as cetrelimab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Giving niraparib with or without cetrelimab, after treatment with cabazitaxel, carboplatin, and cetrelimab, may help control aggressive variant prostate cancer.

Conditions

Aggressive Variant Prostate Carcinoma; Castration-Resistant Prostate Carcinoma; Metastatic Prostate Carcinoma; Metastatic Prostate Neuroendocrine Carcinoma; Metastatic Prostate Small Cell Carcinoma; Stage IV Prostate Cancer AJCC v8

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  Estimated by the methods of Kaplan and Meier. The 2 randomized treatment arms will be compared by a log rank test.

  Time from randomization until documented disease progression, start of new therapy for prostate cancer in the absence of progression, or death in the absence of progression, whichever comes first, assessed up to 5 years

Secondary Outcomes (5)

• Overall survival (OS)

  Time from randomization until death or last contact, assessed up to 5 years

• Response rate

  Up to 5 years

• Response rate

  Up to 5 years

• Response rate by circulating tumor cells

  Up to 5 years

• Incidence of adverse events

  Up to 30 days after last administration of study drug

Study Arms (2)

Group I (niraparib)

EXPERIMENTAL

INDUCTION: Patients receive cabazitaxel IV over 60 minutes and carboplatin IV over 60 minutes on day 1. Beginning cycle 2, patients also receive cetrelimab IV over 30-60 minutes on day 1. Treatment repeats for up to 6 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive niraparib orally PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Cabazitaxel; Drug: Carboplatin; Biological: Cetrelimab; Drug: Niraparib

Group II (cetrelimab, niraparib)

EXPERIMENTAL

INDUCTION: Patients receive cabazitaxel IV over 60 minutes and carboplatin IV over 60 minutes on day 1. Beginning cycle 2, patients also receive cetrelimab IV over 30-60 minutes on day 1. Treatment repeats for up to 6 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive cetrelimab IV over 30 minutes on day 1 and niraparib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Cabazitaxel; Drug: Carboplatin; Biological: Cetrelimab; Drug: Niraparib

Interventions

Cabazitaxel DRUG

Given IV

Also known as: Jevtana, RPR-116258A, Taxoid XRP6258, XRP-6258

Group I (niraparib); Group II (cetrelimab, niraparib)

Carboplatin DRUG

Given IV

Also known as: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo

Group I (niraparib); Group II (cetrelimab, niraparib)

Cetrelimab BIOLOGICAL

Given IV

Also known as: JNJ 63723283, JNJ-63723283, JNJ63723283, WHO 10757

Group I (niraparib); Group II (cetrelimab, niraparib)

Niraparib DRUG

Given PO

Also known as: MK-4827, MK4827

Group I (niraparib); Group II (cetrelimab, niraparib)

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• 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
• 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:
• Histologically proven small cell (neuroendocrine) prostate carcinoma
• Exclusive visceral metastases
• Predominantly lytic bone metastases identified by plain x-ray or CT scan
• Bulky (\>= 5 cm in longest dimension) lymphadenopathy or high-grade tumor mass in prostate/pelvis
• Low PSA (=\< 10 ng/mL) at initial presentation (prior to androgen ablation or at symptomatic progression in the castrate-setting) plus high volume (\>= 20) bone metastases
• Elevated serum lactate dehydrogenase (LDH) (\>= 2 x ULN) or elevated serum carcinoembryonic antigen (CEA) (\>= 2 x ULN) in the absence of other etiologies
• Short interval (=\< 180 days) to castrate-resistant progression following initiation of hormonal therapy
• Known loss or mutation (by Clinical Laboratory Improvement Act \[CLIA\] certified molecular testing, immunohistochemistry \[IHC\] and/or deoxyribonucleic acid \[DNA\] sequencing) in at least 2 of Tp53, RB1 and PTEN defined as:
• AVPC determination by immunohistochemistry. As previously described, 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

You may not qualify if:

• Any prior treatment for castration-resistant prostate cancer (CRPC) with carboplatin, cisplatin, cabazitaxel, PARP-inhibitor or an anti-PD1 or anti-PDL1 inhibitor
• Patients who have received more than one line of chemotherapy. Any number of prior hormonal or targeted therapies are allowed
• Patients who have not recovered from adverse events secondary to systemic therapy (except for luteinizing hormone-releasing hormone \[LHRH\] 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 (Common Terminology Criteria for Adverse Events \[CTCAE\] 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)
• History or current diagnosis of MDS/AML
• 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 pneumonitis or 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 high resolution computed tomography (HRCT) scan, uncontrolled seizures, history of allogeneic organ transplant, history of primary immunodeficiency or any psychiatric disorder that prohibits obtaining informed consent
• Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication
• Patients with symptomatic uncontrolled brain metastases or spinal cord compressions. A scan to confirm the absence of brain metastases is not required. The patient can receive a stable dose of corticosteroids before and during the study as long as these were started at least 28 days prior to treatment
• Patients with a known hypersensitivity to niraparib, carboplatin, cabazitaxel or an anti-PD1 or anti-PDL1 inhibitor
• Current or prior use of immunosuppressive medication within 28 days before the first dose of cetrelimab, with the exceptions of intranasal and inhaled corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid or steroids as pre-medication for hypersensitivity reactions (e.g. CT scan premedication)
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.\]). The following are exceptions to this criterion:

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• Janssen Pharmaceutica: collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

cabazitaxel; XRP6258; Carboplatin; niraparib

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

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 12, 2020
• First Posted: October 19, 2020
• Study Start: December 29, 2020
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: December 23, 2025

Record last verified: 2025-12

Locations

US (1)