Pembrolizumab and Lenvatinib in Advanced/Metastatic Neuroendocrine Prostate Cancer (PLANE-PC)
Primary Purpose
Prostate Cancer Metastatic, Neuroendocrine Tumors
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Pembrolizumab
Lenvatinib
Sponsored by
About this trial
This is an interventional treatment trial for Prostate Cancer Metastatic
Eligibility Criteria
Inclusion Criteria:
- 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.
- 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
- 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.
- Projected life expectancy of at least 6 months as determined by treating physician.
- 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:
- 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.
- Severe hypersensitivity (≥ Grade 3) to lenvatinib and/or any of its excipients.
- 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
- History of severe (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
- Active uncontrolled infection.
- 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.
- Known history of Human Immunodeficiency Virus (HIV). NOTE: HIV testing is not required unless mandated by a local health authority.
- 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.
- Known history of active TB (Bacillus Tuberculosis).
Sites / Locations
- City of HopeRecruiting
- Winship Cancer Instituted of Emory UniversityRecruiting
- University of Michigan Health SystemRecruiting
- Oregon healthRecruiting
- Froedtert and The Medical College of WisconsinRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Study Treatment Arm
Arm Description
Lenvatinib 20 mg Orally Day1-21 with Pembrolizumab 200 mg Intravenously (IV) over 30 minutes Day 1. Each cycle = 21 days
Outcomes
Primary Outcome Measures
Radiologic Progression Free Survival (rPFS) for soft tissue lesions
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.
Radiologic Progression Free Survival (rPFS) for bone lesions
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
Frequency and Severity of adverse events
Frequency and severity of adverse events as measured by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Overall Survival (OS)
Overall survival (OS) will be measured from date of registration to date of death from any cause.
Objective Response Rate (ORR)
ORR will be the proportion of patients achieving either a complete response or a partial response
Duration of Response (DoR)
DOR will be measured from the start date of the best response achieved until the date of relapse
Full Information
NCT ID
NCT04848337
First Posted
April 9, 2021
Last Updated
September 26, 2023
Sponsor
University of Michigan Rogel Cancer Center
Collaborators
Merck Sharp & Dohme LLC, Hoosier Cancer Research Network
1. Study Identification
Unique Protocol Identification Number
NCT04848337
Brief Title
Pembrolizumab and Lenvatinib in Advanced/Metastatic Neuroendocrine Prostate Cancer
Acronym
PLANE-PC
Official Title
Phase II Trial of Pembrolizumab and Lenvatinib in Advanced/Metastatic Neuroendocrine Prostate Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 25, 2021 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Michigan Rogel Cancer Center
Collaborators
Merck Sharp & Dohme LLC, Hoosier Cancer Research Network
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Prostate Cancer Metastatic, Neuroendocrine Tumors
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Study Treatment Arm
Arm Type
Experimental
Arm Description
Lenvatinib 20 mg Orally Day1-21 with Pembrolizumab 200 mg Intravenously (IV) over 30 minutes Day 1. Each cycle = 21 days
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab
Other Intervention Name(s)
Keytruda
Intervention Description
Pembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks.
Intervention Type
Drug
Intervention Name(s)
Lenvatinib
Other Intervention Name(s)
Lenvima
Intervention Description
Lenvatinib 20 mg orally daily.
Primary Outcome Measure Information:
Title
Radiologic Progression Free Survival (rPFS) for soft tissue lesions
Description
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.
Time Frame
2 years
Title
Radiologic Progression Free Survival (rPFS) for bone lesions
Description
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.
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Frequency and Severity of adverse events
Description
Frequency and severity of adverse events as measured by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Time Frame
2 years
Title
Overall Survival (OS)
Description
Overall survival (OS) will be measured from date of registration to date of death from any cause.
Time Frame
2 years
Title
Objective Response Rate (ORR)
Description
ORR will be the proportion of patients achieving either a complete response or a partial response
Time Frame
2 years
Title
Duration of Response (DoR)
Description
DOR will be measured from the start date of the best response achieved until the date of relapse
Time Frame
2 years
10. Eligibility
Sex
Male
Gender Based
Yes
Gender Eligibility Description
prostate cancer
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
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
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.
Projected life expectancy of at least 6 months as determined by treating physician.
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:
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.
Severe hypersensitivity (≥ Grade 3) to lenvatinib and/or any of its excipients.
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
History of severe (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
Active uncontrolled infection.
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.
Known history of Human Immunodeficiency Virus (HIV). NOTE: HIV testing is not required unless mandated by a local health authority.
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.
Known history of active TB (Bacillus Tuberculosis).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ulka Vaishampayan, MD
Phone
734-936-7813
Email
vaishamu@med.umich.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Brittany Brugh
Phone
317-634-5842
Ext
13
Email
bbrugh@hoosiercancer.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ulka Vaishampayan, MD
Organizational Affiliation
University of Michigan
Official's Role
Principal Investigator
Facility Information:
Facility Name
City of Hope
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Genesis Hampton-Schooling
Email
ghamptonschooli@coh.org
First Name & Middle Initial & Last Name & Degree
Tanya Dorff, MD
Facility Name
Winship Cancer Instituted of Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Victor Edet
Phone
404-251-0627
Email
victor.asuquo.edet@emory.edu
First Name & Middle Initial & Last Name & Degree
Bassel Nazha, MD
Facility Name
University of Michigan Health System
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Charles Leister
Phone
734-232-2464
Email
cleister@med.umich.edu
First Name & Middle Initial & Last Name & Degree
Ulka Vaishampayan, MD
Facility Name
Oregon health
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
OHSU Knight Cancer Institute Clinical Trials
Email
trails@ohsu.edu
First Name & Middle Initial & Last Name & Degree
Alexandra Sokolova
Facility Name
Froedtert and The Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53226
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Megan Memmel
Email
mmemmel@mcw.edu
First Name & Middle Initial & Last Name & Degree
Kathryn Bylow, MD
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Pembrolizumab and Lenvatinib in Advanced/Metastatic Neuroendocrine Prostate Cancer
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