Pembrolizumab With Combination Chemotherapy in Treating Participants With Locally Advanced or Metastatic Small Cell/Neuroendocrine Cancers of Urothelium or Prostate

NCT03582475 | Active Not Recruiting Phase 1 Results DMC FDA Drug

• 2 other identifiers: 18-000435NCI-2018-01120
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This phase Ib trial studies how well pembrolizumab works with combination chemotherapy in treating participants with small cell/neuroendocrine cancers of the urothelium or prostate that has spread to nearby tissue or lymph nodes or that has spread to other places in the body. Monoclonal antibodies, such as pembrolizumab, may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as etoposide, docetaxel, cisplatin, 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. Giving pembrolizumab with platinum-based chemotherapy may work better in treating participants with small cell/neuroendocrine cancers of the urothelium or prostate.

Conditions

Bladder Small Cell Neuroendocrine Carcinoma; Castration-Resistant Prostate Carcinoma; Metastatic Bladder Urothelial Carcinoma; Metastatic Urethral Urothelial Carcinoma; Prostate Carcinoma Metastatic in the Bone; Prostate Neuroendocrine Neoplasm; Prostate Small Cell Carcinoma; Stage III Bladder Cancer American Joint Committee on Cancer ( AJCC) v8; Stage III Prostate Cancer AJCC v8; Stage III Urethral Cancer AJCC v8; Stage IV Bladder Cancer AJCC v8; Stage IV Prostate Cancer AJCC v8; Stage IV Urethral Cancer AJCC v8; Stage IVA Bladder Cancer AJCC v8; Stage IVB Bladder Cancer AJCC v8; Ureter Small Cell Carcinoma; Urothelial Carcinoma

Outcome Measures

Primary Outcomes (7)

• Durable Response Rate (DRR) (Cohorts 1 and 2)

  Durable Response Rate (DRR) defined as the proportion of patients who achieved a confirmed complete or partial response (CR or PR) and maintained that response for at least 6 months.

  At 6 months

• Overall Response Rate (ORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (Cohorts 1 and 2)

  Overall Response Rate (ORR) defined as patients by Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 exhibited a complete or partial response (CR or PR). CR defined as disappearance of all target lesions. PR defined as \>= 30% decrease in sum of the longest diameter of target lesions. .

  Up to 3 years

• Duration of Response (DOR) Per RECIST 1.1 (Cohorts 1 and 2)

  Duration of Response (DOR) defined as the time from the first documented CR or PR until radiograph disease progression or Prostate-Specific Antigen (PSA) progression.

  From the first documented CR or PR up to 3 years

• Proportion of Participants With Progression Free Survival at 12 and 24 Months

  Progression Free Survival (PFS) defined as the time from the first day of study treatment to first documented disease progression by Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1 as a 20% increase in the sum of the longest diameter of target lesions, a measurable increase in a non-target lesion, or the appearance of new lesion(s).

  12 months and 24 months.

• Proportion of Participants With Overall Survival of Cohort 1 and 2 at 12 and 24 Months

  Overall Survival (OS) defined as the time from the first day of study treatment to the time of death from any cause.

  12 months and 24 months.

• Portion of Participants With Radiographic Progression-free Survival (rPFS) by Prostate Cancer Working Group 3 (PCWG3) at 12 and 24 Months (Cohort 2)

  PCWG3 is specifically designed for prostate cancer and incorporates both soft tissue and bone response assessment. RECIST 1.1 is used for evaluating responses in solid tumors, while PCWG3 combines Response evaluation criteria in solid tumors (RECIST)1.1 for soft tissue assessment with specific criteria for bone scans. The PCWG3 response criteria was used to report the portion of participants with rPFS at their 12 and 24 month assessments.

  12 months and 24 months.

• Percentage of Participants With Adverse Events Per Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 (Cohorts 1 and 2)

  Up to 3 years

Other Outcomes (1)

• Percentage of Participants With Programmed Death-ligand 1 (PD-L1) Combined Positive Score (CPS) Greater Than 10, at 12 Months

  at 12 months

Study Arms (1)

Treatment (pembrolizumab, platinum-based chemotherapy)

EXPERIMENTAL

Participants receive pembrolizumab IV over 30 minutes on day 1. Courses repeat every 3 weeks for 2 years in the absence of disease progression or unacceptable toxicity. Participants also receive standard of care chemotherapy comprising either etoposide IV on days 1-3 and cisplatin IV or carboplatin IV on day 1 (Cohort 1), or etoposide IV on days 1-3, carboplatin IV on day 1, and docetaxel IV on day 1 (Cohort 2). Treatment repeats every 3 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Drug: Carboplatin; Drug: Cisplatin; Drug: Docetaxel; Drug: Etoposide; Biological: Pembrolizumab

Interventions

Carboplatin DRUG

Given IV

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

Treatment (pembrolizumab, platinum-based chemotherapy)

Cisplatin DRUG

Given IV

Also known as: Abiplatin, Blastolem, Briplatin, CDDP, Cis-diammine-dichloroplatinum, Cis-diamminedichloridoplatinum, Cis-diamminedichloro Platinum (II), Cis-diamminedichloroplatinum, Cis-dichloroammine Platinum (II), Cis-platinous Diamine Dichloride, Cis-platinum, Cis-platinum II, Cis-platinum II Diamine Dichloride, Cismaplat, Cisplatina, Cisplatinum, Cisplatyl, Citoplatino, Citosin, Cysplatyna, DDP, Lederplatin, Metaplatin, Neoplatin, Peyrone's Chloride, Peyrone's Salt, Placis, Plastistil, Platamine, Platiblastin, Platiblastin-S, Platinex, Platinol, Platinol- AQ, Platinol-AQ, Platinol-AQ VHA Plus, Platinoxan, Platinum, Platinum Diamminodichloride, Platiran, Platistin, Platosin

Treatment (pembrolizumab, platinum-based chemotherapy)

Docetaxel DRUG

Given IV

Also known as: Docecad, RP56976, Taxotere, Taxotere Injection Concentrate

Treatment (pembrolizumab, platinum-based chemotherapy)

Etoposide DRUG

Given IV

Also known as: Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16-213, VP-16, VP-16-213

Treatment (pembrolizumab, platinum-based chemotherapy)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (pembrolizumab, platinum-based chemotherapy)

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed diagnosis of locally advanced or metastatic 1) naive small cell cancer of the bladder, urethra, or upper urinary tract, or 2) primary small cell or neuroendocrine prostate cancer will be enrolled in this study.
• Histological diagnosis of pure or mixed small cell or neuroendocrine cancer by a genitourinary pathologist is sufficient and confirmatory immunohistochemistry is not required.
• Cohort 1 will include subjects with no prior systemic chemotherapy for locally advanced or metastatic urothelial carcinoma, with the following exception(s):
• Platinum-based chemotherapy with recurrence \> 12 months from completion of therapy is permitted.
• Cohort 2 will include subjects with no prior systemic chemotherapy for primary small cell prostate cancer, with the following exception(s):
• Platinum-based chemotherapy with recurrence \> 12 months from completion of therapy is permitted.
• Cohort 2 will include subjects with prior treatments for metastatic castration-resistant prostate cancer (mCRPC) including:
• Prior chemotherapy with 2 other agents is allowed if \> 6 months elapsed from last dose (if docetaxel chemotherapy is used more than once for hormone-sensitive and for mCRPC it will be considered 1 therapy).
• Ongoing androgen deprivation therapy with up to 2 second-generation hormonal manipulations (e.g. including but not limited to abiraterone acetate and/or enzalutamide).
• Ongoing treatment with for bone metastasis (e.g. denosumab or zoledronic acid) is permitted.
• Prior immunotherapy with sipuleucel-T is allowed if completed \> 4 weeks prior to trial enrollment.
• A male participant must agree to use contraception during the treatment period and for at least 120 days after the last dose of pembrolizumab or 180 days after chemotherapy and refrain from donating sperm during this period.
• A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP) or
• A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 120 days after the last dose of pembrolizumab or 180 days after chemotherapy.

You may not qualify if:

• Has disease suitable for local treatment with curative intent.
• A WOCBP who has a positive urine pregnancy test within 72 hours prior to receiving the first dose of trial medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g. CTLA-4, OX-40, CD137).
• Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to first dose of trial treatment.
• Note: Participants must have recovered from all AEs due to previous therapies to =\< grade 1 or baseline. Participants with =\< grade 2 neuropathy may be eligible.
• Note: If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
• Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (=\< 2 weeks of radiotherapy) to non-central nervous system (CNS) disease.
• Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette?Guerin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist) are live attenuated vaccines and are not allowed.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
• Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
• For Cohort 1, a history of prostate cancer that was identified incidentally following cystoprostatectomy for bladder cancer is acceptable provided that the PSA is \< 0.2.
• Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment.
• Has severe hypersensitivity (\>= grade 3) to pembrolizumab and/or any of its excipients.

Sponsors & Collaborators

• Jonsson Comprehensive Cancer Center: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

UCLA / Jonsson Comprehensive Cancer Center

Los Angeles, California, 90095, United States

Location

Related Publications (1)

• Gu Y, Ly A, Rodriguez S, Zhang H, Kim J, Mao Z, Sachdeva A, Zomorodian N, Pellegrini M, Li G, Liu S, Drakaki A, Rettig MB, Chin AI. PD-1 blockade plus cisplatin-based chemotherapy in patients with small cell/neuroendocrine bladder and prostate cancers. Cell Rep Med. 2024 Nov 19;5(11):101824. doi: 10.1016/j.xcrm.2024.101824. Epub 2024 Nov 12.

  PMID: 39536751 DERIVED

MeSH Terms

Conditions

Prostatic Neoplasms; Urethral Neoplasms; Urinary Bladder Neoplasms; Carcinoma, Transitional Cell

Interventions

Carboplatin; Cisplatin; 1,2-diaminocyclohexaneplatinum II citrate; Platinum; Docetaxel; Etoposide; pembrolizumab

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Urologic Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urethral Diseases; Urologic Diseases; Urinary Bladder Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Metals, Heavy; Elements; Transition Elements; Metals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Results Point of Contact

• Title: Sara Rodriguez
• Organization: UCLA / Department of Radiology

SaraRodriguez@mednet.ucla.edu

310-794-2877

Study Officials

• Arnold Chin

  UCLA / Jonsson Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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: June 13, 2018
• First Posted: July 11, 2018
• Study Start: January 11, 2019
• Primary Completion: December 1, 2025
• Study Completion (Estimated): December 1, 2026
• Last Updated: November 12, 2025
• Results First Posted: June 10, 2025

Record last verified: 2025-11

Locations

US (1)