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New treatment option for Neuroendocrine Tumors
Official title Lenvatinib Plus Pembrolizumab in Well Differentiated G3 Neuroendocrine Tumors
ClinicalTrials.gov ID: NCT05746208
What this study is testing
What is Lenvatinib?
Lenvatinib is an investigational medicine, given as an infusion into a vein, being studied as a potential treatment for neuroendocrine tumors.
Also referred to as Lenvima.
Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- This is the first study to be done in a newly described class of neuroendocrine tumors known as well-differentiated grade 3 neuroendocrine tumors (WD G3 NET). First described in the pancreas in 2017, the classification was broadened to include gastrointestinal tract tumors in 2019.
- Phase 2: a mid-size study of how well it works
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 and older
You may be able to join if
- Participants must have locally advanced or unresectable histologically or cytologically confirmed WD G3 NET.
- pancreas primary.
- other primary sites:
- gastrointestinal site,
- unknown primary site,
You likely can't join if
- Has poorly differentiated neuroendocrine carcinoma (e.g., small cell NEC, large cell NEC, Merkel cell carcinoma, prostate neuroendocrine carcinoma)...
- Uncontrolled blood pressure (BP) (Systolic BP \>=140 mmHg or diastolic BP \>=90 mmHg) despite an optimized regimen of antihypertensive medication.
- Significant gastrointestinal malabsorption or any other condition that might affect the absorption of lenvatinib.
- Has pre-existing \>= grade 3 (G3) gastrointestinal or non-gastrointestinal fistula.
- Has clinically significant cardiovascular disease within 12 months from the first dose of study intervention, including New York Heart Association...
- Radiographic evidence of major blood vessel invasion/infiltration (e.g., carotid artery) or intratumoral cavitation in the chest (e.g. tumors above...
See the full eligibility criteria
Who can join
- Participants must have locally advanced or unresectable histologically or cytologically confirmed WD G3 NET.
- pancreas primary.
- other primary sites:
- gastrointestinal site,
- unknown primary site,
- lung neuroendocrine carcinoma with carcinoid morphology, or
- other non-pancreatic primary sites with well-differentiated (WD) morphology and Ki67 \> 20%.
- WD G3 NET occurring de novo or in the setting of grade progression allowed (provided WD G3 NET is thought to be the dominant histology at the time of enrollment).
- Tumors with ambiguous histology and/or Ki67 \>/=55% must be reviewed at the participating site to confirm that they are not poorly differentiated. Tumors with confirmed ambiguous histology will be considered eligible.
- At least 1 measurable target lesion according to RECIST 1.1, including the following criteria.
- non-nodal lesion that measures \>=1.0 cm in the longest diameter.
- lymph node (LN) lesion that measures as \>=1.5 cm in the short axis.
- the lesion is suitable for repeat measurement using computed tomography (CT) / magnetic resonance imaging (MRI) (CT/MRI).
- lesions previously treated with radiation or other locoregional therapy are considered measurable if progression has been demonstrated in such lesions.
- in the setting of grade progression, every attempt should be made to select measurable target lesions that are thought to represent G3 disease (based on biopsy results, tumor growth rate, or other features).
- Eligibility for HP 13C MR (applicable only to UCSF patients who meet the requirements below)- up to 10 patients (if machine is functional, available and scheduling allows):
- At least 1 lesion that is deemed suitable for imaging by HP 13C MR by the investigators (ideally separate from the biopsy site, if planned).
- No contraindications to MRI.
- No prior local therapy to the target lesions (s) -unless clear progression in the lesions(s).
- NOTE: University of California, San Francisco (UCSF) patients who do not meet this requirement will still be allowed to participate if they otherwise meet all eligibility requirements (this criterion should be recorded...
- Radiographic evidence of progressive disease within 6 months. a. Required unless 1L in the setting of clinically significant tumor burden and/or tumor with unfavorable biology (e.g. Ki67 \>/=55%, rapid growth rate...
- Age \>=18 years. a. Because no dosing or adverse event data are currently available on the use of lenvatinib plus pembrolizumab in patients \<18 years of age, children are excluded from this study but will be eligible...
- Eastern Cooperative Oncology Group (ECOG) performance status \<= 1.
- Have adequate organ function as defined below (Specimens must be collected within 14 days prior to the start of study treatment):
- Adequate bone marrow function:
- Absolute neutrophil count \>=1,500/microliter (mcL)
- Platelets \>=100,000/mcL
- Hemoglobin \>=1,500/mcL
- Hemoglobin \>=9.0 g/dL or \>=5.6 mmol/L.
- Adequate hepatic function,
- Total bilirubin \<=1.5 X institutional upper limit of normal, unless elevated due to Gilbert's syndrome and direct bilirubin is within normal limits.
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase (SGPT) \<=2.5 X institutional upper limit of normal (ULN) (\<=5 ×...
- Adequate renal function,
- Creatinine \<= 1.5 x institutional upper limit of normal OR
- Creatinine clearance \>=30 mL/min for participant with creatinine levels \>1.5 × institutional ULN,
- Urine protein-to-creatinine ratio (UPCR) \<1 (unless urine protein \<1 g/24 hour) OR
- Urine protein dipstick \<= 1+(unless urine protein \<1 g/24 hour).
- Coagulation: International normalized ratio (INR) OR prothrombin time (PT) Activated partial thromboplastin time (aPTT) or partial thromboplastin time (PTT) \<=1.5 × ULN unless participant is receiving anticoagulant...
- Participant (or legally acceptable representative) must have the ability to understand a written informed consent document, and the willingness to sign it.
- Adequately controlled blood pressure (BP) with or without anti-hypertensive medications, defined as BP \<140/90 (NOTE: BP should be controlled without a change in medications within one week of day 1 cycle 1).
- Individuals with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or how well it works assessment of the investigational regimen are eligible...
- Must have a life expectancy of greater than 3 months, as determined by the investigator.
- Stage 2 patients must agree to have a biopsy of the primary tumor or metastatic tissue at baseline, and there must be a lesion that can be biopsied with acceptable clinical risk (as judged by the investigator).
- Patients with unsuccessful baseline biopsies may undergo an additional biopsy attempt (at the same or a different site, determined by the investigator).
- If no metastatic site can be safely biopsied, a biopsy of the primary tumor is acceptable, but must be approved by the principal investigator.
- Baseline tumor biopsy may be omitted if the tumor is inaccessible and/or a biopsy is thought to post high procedural risk due to location or other factors; or If participants have only 1 small (\<1.5cm) measurable...
- If fresh tumor tissue cannot be collected, the overall study (lead-site) PI may approve the use of archival tissue. The use of archival tissue in lieu of a fresh tumor biopsy is encouraged and will be evaluated on a...
- Formalin-fixed, paraffin-embedded (FFPE) tissue blocks are preferred to slides. Newly obtained biopsies are preferred to archived tissue.
- Male participants are eligible to participate if they agree to the following starting with the first dose of study therapy through 7 days after the last dose of lenvatinib (and refrain from donating sperm during this...
- Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent OR Must agree to use contraception (see appendix 5) unless...
- Agree to use a male condom plus partner use of an additional contraceptive method when having penile-vaginal intercourse with a WOCBP who is not currently pregnant. Note: Men with a pregnant or breastfeeding partner...
- Please note that 7 days after lenvatinib is stopped, if the participant is on pembrolizumab only, no male contraception measures are needed.
- Female participants are eligible if not pregnant or breastfeeding, and at least 1 of the following conditions applies during the intervention period and for at least 120 days post pembrolizumab or 30 days post...
- Not be a woman of childbearing potential (WOCBP), e.g., postmenopausal (no menses for \> 1 year) or permanently sterilized.
- Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of \<1% per year), with low user dependency.
- Abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) NOTE: The investigator should evaluate the potential for contraceptive method failure (i.e...
What rules you out
- Has poorly differentiated neuroendocrine carcinoma (e.g., small cell NEC, large cell NEC, Merkel cell carcinoma, prostate neuroendocrine carcinoma) or WD Grades 1 or 2 NET (without evidence of G3 NET).
- Uncontrolled blood pressure (BP) (Systolic BP \>=140 mmHg or diastolic BP \>=90 mmHg) despite an optimized regimen of antihypertensive medication.
- Significant gastrointestinal malabsorption or any other condition that might affect the absorption of lenvatinib.
- Has pre-existing \>= grade 3 (G3) gastrointestinal or non-gastrointestinal fistula.
- Has clinically significant cardiovascular disease within 12 months from the first dose of study intervention, including New York Heart Association (NYHA) Class III or IV congestive heart failure, unstable angina...
- Radiographic evidence of major blood vessel invasion/infiltration (e.g., carotid artery) or intratumoral cavitation in the chest (e.g. tumors above the diaphragm). The degree of tumor invasion/infiltration of major...
- Portal vein or inferior vena cava involvement by tumor is allowed at the discretion of the investigator (and is distinguished from invasion through the wall of a vessel.
- Vascular encasement by tumor below diaphragm is allowed at the discretion of the investigator, Examples of potentially eligible tumors include: mesenteric mass encasing superior mesenteric artery (SMA)/superior...
- Vascular encasement by the tumor in the abdomen, such as a mesenteric mass encasing the SMV/SMA, must be distinguished from invasion through the wall of a vessel and with consideration of the potential risk of severe...
- Active hemoptysis or tumor bleeding (bright red blood of at least 0.5 teaspoons) within 3 weeks prior to the first dose of study drug.
- Hypersensitivity (\>=G3) or known intolerance to lenvatinib or pembrolizumab or any of its excipients.
- Serious non-healing wound, ulcer, or bone fracture.
- Bleeding or thrombotic disorders or participants at risk for severe hemorrhage.
- 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...
- Known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
- Individuals with new or progressive asymptomatic small (\<1 cm) brain metastases are eligible if the treating physician determines that immediate CNS-specific treatment is not required and is unlikely to be required...
- Participants with previously treated brain metastases (e.g., whole brain radiation therapy, surgery, or radiosurgery) may participate provided they are radiologically stable (i.e., without evidence of progression by...
- Has an 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). a.Replacement therapy (e.g...
- Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
- Has an active infection requiring systemic therapy.
- Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by a local health authority.
- Has a known history of hepatitis B (defined as hepatitis B surface antigen (HBsAg) reactive) or known active hepatitis C virus (HCV) (defined as HCV RNA [qualitative] is detected) infection. Note: No testing for...
- Participants with controlled hepatitis C are eligible (no detectable HCV RNA qualitative) provided anti-viral therapy completed at least 4 weeks prior to enrollment.
- Participants with controlled HBV are eligible if they meet the following criteria:
- Antiviral therapy for HBV must be given for at least 4 weeks and HBV viral load must be less than 500 IU/mL before the first dose of study drug. Participants on active HBV therapy with viral loads under 100 IU/mL should...
- Participants who are positive for anti-Hepatitis B Core (HBc), negative for HbsAg, and negative or positive for anti-HBs, and who have an HBV viral load under 100 IU/mL, do not require HBV antiviral prophylaxis
- Is known to have active tuberculosis (TB, Bacillus tuberculosis).
- Diagnostic assessments:
- Participants with urine protein creatinine ratio (UPCR) \>1 or proteinuria \>-2+ (\>=100 mg/dL) on urinalysis/urine dipstick testing will undergo 24-hour urine collection for quantitative assessment of proteinuria...
- Prolongation of QTc interval to \> 480 milliseconds (ms). Investigator may use the average of 3 triplicates if screening QTc \> 450 ms. Rescreening is allowed after discontinuation of any drugs known to prolong QTc...
- Left ventricular ejection fraction (LVEF) below the institutional (or local laboratory) normal range as determined by multigated acquisition scan (MUGA) or echocardiogram (ECHO).
- Pregnant women are excluded from this study because lenvatinib plus pembrolizumab are products with the potential for teratogenic or abortifacient effects.
- A woman of child bearing potential (WOCBP) must have a negative highly sensitive pregnancy test (urine or serum) within 14 days of the first dose of the study intervention.
- If a urine test cannot be confirmed as negative (e.g., a positive or an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy...
- Similarly, a WOCBP must have a negative urine pregnancy test if the serum pregnancy test is positive (and thought to be spurious/from underlying malignancy).
- Women who are breastfeeding are excluded from the study because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with lenvatinib plus pembrolizumab...
- Has a history or current evidence of any condition, therapy, or laboratory abnormality (including electrolyte abnormalities that have not been corrected, e.g., potassium, calcium, magnesium) that might confound the...
- Has known psychiatric or substance abuse disorders that would interfere with cooperating with the requirements of the study. Listed below are specific concomitant therapies or vaccinations that are prohibited during the...
- Currently participating in or has participated in a trial of an investigational device within 4 weeks prior to the first dose of trial treatment.
- Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks or 5 times the half-life time, whichever is shorter prior to study treatment start. Participants must have recovered from...
- Concomitant administration of hormone therapy for breast cancer, and luteinizing hormone-releasing hormone (LHRH) analogs for prostate cancer allowed.
- Concomitant somatostatin analogs for functional neuroendocrine tumors are allowed as per standard of care assuming a stable dose for at least two months and progressive disease has been documented on that dose.
- Note: Participants who have entered the follow-up phase of an investigational study may participate if it has been 4 weeks after the last dose of the previous investigational agent.
- Has received prior treatment with lenvatinib, or any anti-programmed cell death protein 1 (PD-1), anti-programmed death-ligand 1 (PD-L1), or anti-PD-L2 agent or with an agent directed to another stimulatory or...
- Has received prior radiotherapy within 2 weeks of the start of study treatment. Participants must have recovered from all radiation-related toxicities (to Grade \<=1), not require corticosteroids, and not have had...
- Has had major surgery within 3 weeks prior to the first dose of study interventions. Note: Adequate wound healing after major surgery must be assessed clinically, independent of time elapsed for eligibility.
- Has had an allogeneic tissue/solid organ transplant.
- Patients who are currently receiving medication with a known risk of prolonging the QT interval inducing Torsade's de Pointes (TdP) and the treatment cannot either be discontinued or switched to a different medication...
- Biologic response modifiers (e.g., granulocyte colony-stimulating factor) within 4 weeks before study entry. Chronic erythropoietin therapy is permitted provided that no dose adjustments were made within 2 months before...
- Received a live or attenuated vaccine within 30 days of the planned start of study treatment (C1D1). Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster...
The study team makes the final eligibility decision.
Where it's taking place
- San Francisco, California, United States
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include San Francisco, California, United States. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.