What side effects are associated with this type of intervention?

Common treatments for Neuroendocrine Tumors, such as Lenvatinib and Pembrolizumab, have distinct side effect profiles. Lenvatinib often causes hypertension, proteinuria, diarrhea, fatigue, and decreased appetite. Pembrolizumab can lead to immune-related adverse events including colitis, hepatitis, pneumonitis, endocrinopathies, and skin reactions. When used in combination, these treatments may increase the likelihood of these side effects, requiring careful management to ensure patient well-being.

What prior FDA approvals exist?

The FDA has approved several treatments for Neuroendocrine Tumors (NETs), including Tyrosine Kinase Inhibitors (TKIs) and immune checkpoint inhibitors. Everolimus, a TKI, has been approved for the treatment of advanced NETs of gastrointestinal, lung, and pancreatic origin. Additionally, Pembrolizumab, a PD-1 inhibitor, has shown promise in various cancers and is being studied in combination with Lenvatinib for NETs. These approvals highlight the evolving landscape of targeted and immunotherapy options for NETs.

What other types of research exist?

Promising alternatives to Lenvatinib and Pembrolizumab for Neuroendocrine Tumors in 2024 include: 1) Everolimus, a mTOR inhibitor, which has shown efficacy in patients with progressive NETs. 2) Peptide Receptor Radioligand Therapy (PRRT) using radiolabeled somatostatin analogs like Lutetium Lu-177 Dotatate, particularly for somatostatin receptor-positive tumors. 3) Avelumab, a PD-L1 inhibitor, which has shown durable responses in some NET patients. 4) Cabozantinib, another TKI, which has demonstrated activity in various NETs. These alternatives offer different mechanisms of action and may provide effective treatment options for NET patients.

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Tyrosine Kinase Inhibitor

Pembrolizumab + Lenvatinib for Neuroendocrine Prostate Cancer (PLANE-PC Trial)

Q: What is the mechanism of action of this treatment?

Lenvatinib, a tyrosine kinase inhibitor, targets multiple receptors like VEGFR, FGFR, and PDGFR to inhibit tumor growth and angiogenesis. Pembrolizumab, a PD-1 inhibitor, enhances the immune system's ability to detect and destroy cancer cells by preventing immune evasion. These mechanisms are vital for Neuroendocrine Tumor patients as they provide a dual approach to controlling tumor growth and enhancing immune response, potentially improving treatment outcomes.

Phase 2

Recruiting

Led By Ulka Vaishampayan, MD

Research Sponsored by University of Michigan Rogel Cancer Center

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

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.

Age ≥ 18 years at the time of consent.

Must not have

History of severe (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.

Active uncontrolled infection.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial uses a combination of two drugs, lenvatinib and pembrolizumab, to treat patients with cancer that hasn't responded to other treatments. Lenvatinib stops cancer cells from growing, while pembrolizumab helps the immune system attack the cancer. The combination received accelerated FDA approval in September 2019 for all patients with advanced endometrial cancer who have disease progression following previous treatments. The treatment cycles last a few weeks and can continue for several months unless there are side effects or other reasons to stop.

Who is the study for?

Adults (18+) with advanced/metastatic prostate cancer showing neuroendocrine characteristics, not previously treated with certain therapies like VEGF-TKI or immune checkpoint inhibitors. Participants must have an ECOG performance status of 0 or 1, adequate organ function, and agree to use contraception. Exclusions include active CNS metastases, recent live vaccines, severe cardiovascular issues, uncontrolled infections, other active cancers within the past 3 years.

What is being tested?

The trial tests a combination of Pembrolizumab and Lenvatinib for patients with specific types of prostate cancer. Treatment cycles last 21 days and may continue up to a maximum of 35 cycles unless there's disease progression or unacceptable side effects.

What are the potential side effects?

Potential side effects include high blood pressure; fatigue; liver enzyme changes; protein in urine; risk of bleeding or clotting disorders; possible allergic reactions to the drugs' components; autoimmune responses that could affect lung tissue.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am 18 years old or older.

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My cancer is a type that is hard to identify or has changed its characteristics.

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My kidney function, measured by creatinine levels, is within the normal range.

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My cancer has been identified as small-cell or neuroendocrine prostate cancer.

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My prostate cancer shows high levels of certain markers.

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My cancer has spread to vital organs or I have more than 4 cancer sites with a low PSA.

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I have prostate cancer with spread and specific test results or conditions.

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My genetic test shows RBI deletions or mutations.

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My liver enzymes are within the required range.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have or had severe lung inflammation that needed steroids.

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I do not have an active, uncontrolled infection.

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I do not have serious heart problems like recent heart attacks or severe heart failure.

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I have an immune system disorder or have been on high-dose steroids or other immune-weakening medicines recently.

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I am currently on anti-androgen medication but can stop oral forms if required.

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I have been treated with specific cancer drugs targeting my immune system.

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My blood pressure is high despite taking medication.

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I have an active tuberculosis infection.

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I have wounds from surgery that haven't healed.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Radiologic Progression Free Survival (rPFS) for bone lesions

Radiologic Progression Free Survival (rPFS) for soft tissue lesions

Secondary study objectives

Duration of Response (DoR)

Frequency and Severity of adverse events

Objective Response Rate (ORR)

+1 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Study Treatment ArmExperimental Treatment2 Interventions

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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Lenvatinib

2017

Completed Phase 4

~2070

Pembrolizumab

2017

Completed Phase 3

~3150

0 / 19Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Lenvatinib, a tyrosine kinase inhibitor, targets multiple receptors like VEGFR, FGFR, and PDGFR to inhibit tumor growth and angiogenesis. Pembrolizumab, a PD-1 inhibitor, enhances the immune system's ability to detect and destroy cancer cells by preventing immune evasion. These mechanisms are vital for Neuroendocrine Tumor patients as they provide a dual approach to controlling tumor growth and enhancing immune response, potentially improving treatment outcomes.