Pembrolizumab and Lenvatinib in Advanced/Metastatic Neuroendocrine Prostate Cancer

NCT04848337 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 3 other identifiers: UMCC 2020.106HCRN GU19-385HUM00184431
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 5

Brief Summary

Eligible patients will be treated with the combination of lenvatinib and pembrolizumab. A cycle equals 21 days and therapy will continue until radiographic progression, intolerable toxicity, or patient/physician wishes to discontinue protocol therapy. A maximum of 35 cycles may be administered. On Day 1, when both pembrolizumab and lenvatinib are administered, patients should take the lenvatinib per their normal routine.

Conditions

Prostate Cancer Metastatic; Neuroendocrine Tumors

Outcome Measures

Primary Outcomes (1)

• Radiologic Progression Free Survival (rPFS)

  rPFS is defined as the date of treatment intiation to date of radiologic progression of soft tissue lesions per RECIST 1.1 or death whichever occurs first.

  6 months, with a 1-week window

Secondary Outcomes (4)

• Frequency and Severity of Adverse Events

  2 years

• Overall Survival (OS)

  2 years

• Objective Response Rate (ORR)

  2 years

• Duration of Response (DoR)

  2 years

Study Arms (1)

Study Treatment Arm

EXPERIMENTAL

Lenvatinib 20 mg Orally Day1-21 with Pembrolizumab 200 mg Intravenously (IV) over 30 minutes Day 1. Each cycle = 21 days

Drug: Pembrolizumab; Drug: Lenvatinib

Interventions

Pembrolizumab DRUG

Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks.

Also known as: Keytruda

Study Treatment Arm

Lenvatinib DRUG

Lenvatinib 20 mg orally daily.

Also known as: Lenvima

Study Treatment Arm

Eligibility Criteria

• Age: 18 Years+
• Gender Eligibility Details: prostate cancer
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• Age ≥ 18 years at the time of consent.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days prior to the date of registration.
• The subject has histologically proven prostate cancer with radiologic evidence of metastases and at least one of the following:
• Small-cell or NEPC morphology (determined by the enrolling center) on the basis of tissue sample.
• Prostate adenocarcinoma with greater than 50% IHC staining for neuroendocrine markers (e.g., chromogranin and synaptophysin).
• Presence of visceral metastases or high volume disease (\> 4 sites of metastases) with a PSA of ≤ 5.
• Serum chromogranin A level ≥ 5× upper limit of normal (ULN) and/or serum neuron specific enolase (NSE) ≥ 2× ULN.
• RBI deletions or mutations noted on genomic testing.
• Trans-differentiated carcinoma or poorly-differentiated carcinoma.
• Subject has adequate organ function as defined in the table below; all screening labs to be obtained within 10 days prior to Cycle 1 Day 1.
• Absolute neutrophil count (ANC) ≥ 1500/mm3without colony stimulating factor support
• Platelets ≥ 100,000/mm3
• Hemoglobin ≥ 9 g/dL. Transfusions are allowed as needed.
• Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 30 mL/min. For creatinine clearance estimation, the Cockcroft and Gault equation should be used.

You may not qualify if:

• Received prior therapy with VEGF-TKI, immune checkpoint inhibitor, 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 (eg, CTLA-4, OX 40, CD137).
• Received prior systemic anti-cancer therapy including investigational agents within 3 weeks prior to registration. 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.
• Received more than two prior chemotherapy regimens for metastatic prostate cancer. Prior therapy with androgen receptor axis targeted agents is allowed but needs to be discontinued at least 2 weeks prior to study therapy. Prior therapy with Rad-223 or other radiopharmaceuticals is permitted but study therapy should be started at least 4 weeks after the last dose.
• Concurrent treatment with anti-androgen medications. NOTE: LHRH agonists and GNRH antagonists may be continued. All oral anti androgens should be discontinued.
• 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-CNS disease.
• Currently participating in or has participated in a study of an investigational agent or has used an investigational device within 3 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 3 weeks after the last dose of the previous investigational agent.
• Uncontrolled blood pressure (Systolic BP\>140 mmHg or diastolic BP \>90 mmHg) despite an optimized regimen of antihypertensive medication.
• Presence of non-healing wounds after surgical procedures.
• 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.
• Received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed viruses are allowed. All COVID-19 vaccines are permitted at any time before or during the study.
• Significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, unstable angina, myocardial infarction or stroke within 6 months of the first dose of study drug, or cardiac arrhythmia requiring medical treatment at Screening.
• Bleeding or thrombotic disorders or subjects at risk for severe hemorrhage. The degree of tumor invasion/infiltration of major blood vessels (e.g. carotid artery) should be considered because of the potential risk of severe hemorrhage associated with tumor shrinkage/necrosis following lenvatinib therapy.
• Subjects having \> 1+ proteinuria on urine dipstick testing unless a 24-hour urine collection for quantitative assessment indicates that the urine protein is \<1 g/24 hours.
• 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.
• Severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients.

Sponsors & Collaborators

• University of Michigan Rogel Cancer Center: lead
• Merck Sharp & Dohme LLC: collaborator
• Hoosier Cancer Research Network: collaborator

Study Sites (5)

City of Hope

Duarte, California, 91010, United States

Location

Winship Cancer Instituted of Emory University

Atlanta, Georgia, 30322, United States

Location

University of Michigan Health System

Ann Arbor, Michigan, 48109, United States

Location

Oregon health

Portland, Oregon, 97239, United States

Location

Froedtert and The Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Neuroendocrine Tumors

Interventions

pembrolizumab; lenvatinib

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue

Results Point of Contact

• Title: University of Michigan Rogel Cancer Center ClinicalTrials.gov Admin
• Organization: University of Michigan Rogel Cancer Center

clinicaltrialsgov_ccadmin@med.umich.edu

734-936-9499

Study Officials

• Ulka Vaishampayan, MD

  University of Michigan

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: April 9, 2021
• First Posted: April 19, 2021
• Study Start: May 25, 2021
• Primary Completion: January 8, 2025
• Study Completion: April 1, 2026
• Last Updated: February 12, 2026
• Results First Posted: February 12, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)