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Pembrolizumab and Lenvatinib in Advanced/Metastatic Neuroendocrine Prostate Cancer (PLANE-PC)

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ClinicalTrials.gov Identifier: NCT04848337
Recruitment Status : Recruiting
First Posted : April 19, 2021
Last Update Posted : July 16, 2021
Sponsor:
Collaborators:
Merck Sharp & Dohme Corp.
University of Michigan
Information provided by (Responsible Party):
Ulka Vaishampayan, Hoosier Cancer Research Network

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.

Condition or disease Intervention/treatment Phase
Prostate Cancer Metastatic Neuroendocrine Tumors Drug: Pembrolizumab Drug: Lenvatinib Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Trial of Pembrolizumab and Lenvatinib in Advanced/Metastatic Neuroendocrine Prostate Cancer
Actual Study Start Date : May 25, 2021
Estimated Primary Completion Date : October 2022
Estimated Study Completion Date : July 2023


Arm Intervention/treatment
Experimental: Study Treatment Arm
Lenvatinib 20 mg Orally Day1-21 with Pembrolizumab 200 mg Intravenously (IV) over 30 minutes Day 1. Each cycle = 21 days
Drug: Pembrolizumab
Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks.
Other Name: Keytruda

Drug: Lenvatinib
Lenvatinib 20 mg orally daily.
Other Name: Lenvima




Primary Outcome Measures :
  1. Radiologic Progression Free Survival (rPFS) for soft tissue lesions [ Time Frame: 2 years ]
    For soft tissue lesions, 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.

  2. Radiologic Progression Free Survival (rPFS) for bone lesions [ Time Frame: 2 years ]
    For bone lesions, rPFS is defined as the date of treatment initiation to date of progression of bone lesions per PCWG3 criteria or death whichever occurs first.


Secondary Outcome Measures :
  1. Frequency and Severity of adverse events [ Time Frame: 2 years ]
    Frequency and severity of adverse events as measured by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

  2. Overall Survival (OS) [ Time Frame: 2 years ]
    Overall survival (OS) will be measured from date of registration to date of death from any cause.

  3. Objective Response Rate (ORR) [ Time Frame: 2 years ]
    ORR will be the proportion of patients achieving either a complete response or a partial response

  4. Duration of Response (DoR) [ Time Frame: 2 years ]
    DOR will be measured from the start date of the best response achieved until the date of relapse



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Gender Eligibility Description:   prostate cancer
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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.
  2. Age ≥ 18 years at the time of consent.
  3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days prior to the date of registration.
  4. 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).
    • Development of liver metastases in the absence of PSA progression, as defined by Prostate Cancer Working Group 3 criteria.
    • Serum chromogranin A level ≥ 5× upper limit of normal (ULN) and/or serum neuron specific enolase (NSE) ≥ 2× ULN.
  5. 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
    • 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.
    • Bilirubin ≤ 1.5 x the upper limit of normal (ULN) OR direct bilirubin ≤ULN for participants with total bilirubin levels >1.5 × ULN. For subjects with known Gilbert's disease, bilirubin ≤ 3.0 mg/dL
    • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 x ULN if no liver involvement, or ≤ 5 and/or ULN with liver involvement
    • International normalized ratio (INR) OR prothrombin time (PT), Activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
    • Urine protein < 2+ by urine dipstick
  6. A male participant must agree to use of contraception during the treatment period and for at least 120 days after the last dose of study treatment and refrain from donating sperm during this period.
  7. Projected life expectancy of at least 6 months as determined by treating physician.
  8. As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study.

Exclusion Criteria:

  1. 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).
  2. 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.
  3. 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.
  4. Concurrent treatment with anti-androgen medications.
  5. 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.
  6. 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.
  7. Uncontrolled blood pressure (Systolic BP>140 mmHg or diastolic BP >90 mmHg) despite an optimized regimen of antihypertensive medication.
  8. Presence of non-healing wounds after surgical procedures.
  9. 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.
  10. 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-Guérin (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.
  11. 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.
  12. 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.
  13. 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.
  14. 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.
  15. Severe hypersensitivity (≥ Grade 3) to pembrolizumab and/or any of its excipients.
  16. Severe hypersensitivity (≥ Grade 3) to lenvatinib and/or any of its excipients.
  17. Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Replacement steroids for adrenal insufficiency or daily dose equivalent of 10 mg prednisone are allowed
  18. History of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
  19. Active infection requiring systemic therapy.
  20. 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. Subjects with other solid tumors treated curatively and without evidence of recurrence for at least 2 years prior to enrollment may be eligible for study after discussion with the sponsor-investigator.
  21. Known history of Human Immunodeficiency Virus (HIV). NOTE: HIV testing is not required unless mandated by a local health authority.
  22. Known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection. NOTE: Hepatitis B and Hepatitis C testing is not required unless clinical history indicates that this is likely.
  23. Known history of active TB (Bacillus Tuberculosis).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04848337


Contacts
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Contact: Ulka Vaishampayan, MD 734-936-7813 vaishamu@med.umich.edu
Contact: LeaEtta Hyer 13176345842 ext 62 lhyer@hoosiercancer.org

Locations
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United States, Michigan
University of Michigan Health System Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Charles Leister    734-232-2464    cleister@med.umich.edu   
Principal Investigator: Ulka Vaishampayan, MD         
Sponsors and Collaborators
Ulka Vaishampayan
Merck Sharp & Dohme Corp.
University of Michigan
Investigators
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Principal Investigator: Ulka Vaishampayan, MD University of Michigan
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Responsible Party: Ulka Vaishampayan, Sponsor-Investigator, Hoosier Cancer Research Network
ClinicalTrials.gov Identifier: NCT04848337    
Other Study ID Numbers: HCRN GU19-385
First Posted: April 19, 2021    Key Record Dates
Last Update Posted: July 16, 2021
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Prostatic Neoplasms
Neuroendocrine Tumors
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Prostatic Diseases
Pembrolizumab
Lenvatinib
Antineoplastic Agents, Immunological
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action