Lenvatinib and Everolimus in Treating Patients With Advanced, Unresectable Carcinoid Tumors

NCT03950609 | Active Not Recruiting Phase 2 FDA Drug

• 2 other identifiers: 2018-0253NCI-2019-02051
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well lenvatinib and everolimus work in treating patients with carcinoid tumors that have spread to other places in the body (advanced) and cannot be removed by surgery (unresectable). Lenvatinib and everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Conditions

Advanced Carcinoid Tumor; Multiple Endocrine Neoplasia Type 1; Neuroendocrine Neoplasm; Digestive System Neuroendocrine Neoplasm; Unresectable Carcinoid Tumor

Outcome Measures

Primary Outcomes (2)

• Radiographic response rate

  Graded with Response Evaluation Criteria in Solid Tumors version 1.1

  Up to 30 days after completion of study treatment

• Objective response rate

  Up to 30 days after completion of study treatment

Secondary Outcomes (2)

• Progression-free survival

  Up to 30 days after completion of study treatment

• Incidence of adverse events

  Up to 30 days after completion of study treatment

Study Arms (1)

Treatment (lenvatinib, everolimus)

EXPERIMENTAL

Patients receive lenvatinib PO daily and everolimus PO daily on days 1-28. Treatments repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Everolimus; Drug: Lenvatinib

Interventions

Everolimus DRUG

Given PO

Also known as: 42-O-(2-Hydroxy)ethyl Rapamycin, Afinitor, Certican, RAD 001, RAD001, Votubia, Zortress

Treatment (lenvatinib, everolimus)

Lenvatinib DRUG

Given PO

Also known as: E7080, ER-203492-00, Multi-Kinase Inhibitor E7080

Treatment (lenvatinib, everolimus)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed unresectable well differentiated (irrespective of grade) carcinoid tumors. Patients with multiple neuroendocrine tumors associated with MEN1 syndrome will be eligible
• Patients must have radiographically measurable disease. Lesions that have had locoregional therapies such as radiofrequency (RF) ablation, radiation or transarterial therapies must show evidence of progressive disease based on RECIST 1.1 to be deemed a target lesion.
• Patients with other gastrointestinal neuroendocrine tumors must have had progressive disease over the last 12 months irrespective of number of prior therapies. Patients with both functional (who may continue somatostatin analogues as required for control of related symptoms) and non-functional tumors are eligible.
• Written informed consent must be obtained prior to any screening procedures.
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1.
• A sufficient interval must have elapsed between the last dose of prior anti-cancer therapy (including cytotoxic and biological therapies and major surgery) and enrollment, to allow the effects of prior therapy to have abated:
• Cytotoxic or targeted chemotherapy: \>= the duration of the cycle of the most recent treatment regimen (a minimum of 3 weeks for all regimens, except 6 weeks for nitrosoureas and mitomycin-C)
• Biologic therapy (e.g., antibodies): \>= 4 weeks.
• Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L.
• Hemoglobin (Hgb) \>= 9 g/dL.
• Platelets \>= 100 x 10\^9/L.
• Serum total bilirubin =\< 1.5 x upper limit of normal (ULN).
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x ULN, except in patients with tumor involvement of the liver who must have AST and ALT =\< 5 x ULN.
• Serum creatinine =\< 1.5 x ULN or 24-hour clearance \>= 50 mL/min.
• Serum potassium, sodium, magnesium, phosphorus and total calcium (corrected for serum albumin) must be within clinically relevant limits (e.g., a patient can be enrolled if a lab value may be outside the normal laboratory range but the abnormality is not clinically relevant or can be repeated.).

You may not qualify if:

• Patient has a known hypersensitivity to lenvatinib, everolimus or any of their excipients.
• Patients with known or suspected brain metastases. However, if radiation therapy and/or surgery has been completed and serial evaluation by computed tomography (CT) (with contrast enhancement) or magnetic resonance imaging (MRI) over a minimum of 3 months demonstrates the disease to be stable and if the patient remains asymptomatic, then the patient may be enrolled. Such patients must have no need for treatment with steroids or anti-epileptic medications.
• Patients with concurrent malignancies or malignancies within 3 years prior to starting study drug (with the exception of tumors common to a single genetic cancer syndrome, i.e. MEN1, MEN2, vHL, TSC etc., or adequately treated, basal cell skin cancer, squamous cell carcinoma, non-melanoma skin cancer or curatively resected cervical cancer).
• Patient is not able to swallow oral medication and/or has impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the study drugs (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
• Known diagnosis of human immunodeficiency virus (HIV), hepatitis B or hepatitis C (testing is not mandatory).
• Patient who has received radiotherapy within =\< 4 weeks or limited field radiation for palliation within =\< 2 weeks prior to starting study drug, and who has not recovered to grade 1 or better from related side effects of such therapy (exceptions include alopecia) and/or in whom \>= 30% of the bone marrow was irradiated.
• Patient has had major surgery within 21 days prior to starting study drug or has not recovered from major side effects (tumor biopsy is not considered as major surgery).
• Impaired cardiac function or clinically significant cardiac diseases, including any of the following:
• History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis \< 12 months prior to screening
• History of documented congestive heart failure (New York Heart Association functional classification III-IV)
• Documented cardiomyopathy
• Patient has a left ventricular ejection fraction (LVEF) \< 50% as determined by multiple gated acquisition (MUGA) scan or echocardiogram (ECHO) at screening
• History of ventricular, supraventricular, nodal arrhythmias, or any other cardiac arrhythmias, long QT Syndrome or conduction abnormality within 12 months prior to starting study drug
• Congenital long QT syndrome or a family history of QTc prolongation
• On screening, inability to determine the corrected QT interval using Fridericia's formula (QTcF) interval on the electrocardiogram (ECG) (i.e.: unreadable or not interpretable) or QTcF \> 450 msec (using Fridericia's correction).

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• M D Anderson Cancer Center

MeSH Terms

Conditions

Multiple Endocrine Neoplasia Type 1; Neuroendocrine Tumors

Interventions

Everolimus; lenvatinib

Condition Hierarchy (Ancestors)

Multiple Endocrine Neoplasia; Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Neoplasms, Multiple Primary; Neoplastic Syndromes, Hereditary; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Endocrine System Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Nageshwara V Dasari

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

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 23, 2019
• First Posted: May 15, 2019
• Study Start: July 30, 2019
• Primary Completion (Estimated): March 30, 2028
• Study Completion (Estimated): March 30, 2028
• Last Updated: March 19, 2026

Record last verified: 2026-03

Locations

US (1)