What side effects are associated with this type of intervention?

Common treatments for carcinoid tumors include receptor tyrosine kinase inhibitors like lenvatinib and mTOR inhibitors like everolimus. The known side effects of lenvatinib include hypertension, fatigue, diarrhea, decreased appetite, and weight loss. Everolimus can cause side effects such as stomatitis, infections, rash, fatigue, diarrhea, and hyperglycemia. Both treatments may also lead to more severe adverse effects, including liver toxicity and renal impairment, necessitating careful monitoring during therapy.

What prior FDA approvals exist?

The FDA has approved everolimus for the treatment of adults with progressive, well-differentiated, nonfunctional neuroendocrine tumors (NETs) of gastrointestinal tract origin that are unresectable, locally advanced, or metastatic. Everolimus works by inhibiting the mTOR pathway, which is crucial for cell growth and proliferation. Additionally, several small-molecule tyrosine kinase inhibitors (TKIs) targeting angiogenesis, such as sunitinib, sorafenib, pazopanib, lenvatinib, and cabozantinib, have been evaluated in advanced gastrointestinal NETs in phase II trials, showing promising results in disease stabilization and progression-free survival.

What other types of research exist?

Promising novel alternatives to Lenvatinib and Everolimus for treating carcinoid tumors include peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE, somatostatin analogs such as lanreotide and octreotide, and combination chemotherapy regimens like capecitabine and temozolomide (CAPTEM). These treatments have demonstrated efficacy in controlling tumor growth and improving patient outcomes in clinical studies.

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Kinase Inhibitor

Lenvatinib + Everolimus for Neuroendocrine Tumors

Phase 2

Waitlist Available

Led By Nageshwara V Dasari

Research Sponsored by M.D. Anderson Cancer Center

Eligibility Criteria Checklist

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

Must have

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)

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

Must not have

Patient has had major surgery within 21 days prior to starting study drug or has not recovered from major side effects

Patients with concurrent malignancies or malignancies within 3 years prior to starting study drug

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 30 days after completion of study treatment

Awards & highlights

Approved for 10 Other Conditions

All Individual Drugs Already Approved

No Placebo-Only Group

Summary

This trial studies how well lenvatinib and everolimus work in treating patients with advanced carcinoid tumors that cannot be removed by surgery. These medications are taken by mouth and aim to stop cancer cells from growing by blocking essential enzymes. The trial will evaluate how effective and safe these drugs are for these patients. Both lenvatinib and everolimus have shown effectiveness in treating various cancers.

Who is the study for?

This trial is for patients with advanced, unresectable carcinoid tumors. Eligible participants must have well-differentiated tumors, may have MEN1 syndrome, and show disease progression over the last year. They should be in good physical condition (ECOG 0-1), not pregnant, able to swallow pills, without HIV or hepatitis B/C, and free from other cancers in the past 3 years.

What is being tested?

The study tests lenvatinib and everolimus' effectiveness on advanced carcinoid tumors that can't be surgically removed. These drugs aim to inhibit tumor growth by blocking enzymes necessary for cell proliferation.

What are the potential side effects?

Potential side effects of lenvatinib and everolimus include fatigue, diarrhea, high blood pressure, decreased appetite, weight loss, nausea/vomiting; some serious risks are heart damage or severe bleeding.

Eligibility Criteria

Inclusion Criteria

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

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I have waited the required time after my last chemotherapy before starting a new treatment.

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My cancer can be seen on scans and has grown after specific treatments.

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My lung function tests show at least half the normal capacity and my oxygen levels are above 88% without assistance.

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My cancer can be seen on scans and has grown after specific treatments.

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My kidney function is within the normal range.

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My liver tests are within the required range.

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I am fully active or restricted in physically strenuous activity but can do light work.

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I am fully active or restricted in physically strenuous activity but can do light work.

Exclusion Criteria

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

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I haven't had major surgery in the last 3 weeks or still have major side effects from it.

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I haven't had any other cancers in the last 3 years.

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I have or might have cancer that has spread to my brain.

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I have coughed up bright red blood recently.

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I had radiotherapy recently and still experience significant side effects.

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I have been diagnosed with HIV, hepatitis B, or hepatitis C.

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I am currently taking warfarin or a similar blood thinner.

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I have previously been treated with mTOR inhibitors or lenvatinib.

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I am allergic to lenvatinib, everolimus, or their ingredients.

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I am a sexually active male and will use a condom during treatment and for 28 days after.

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I have heart problems that affect my daily activities.

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I cannot take pills by mouth or have a stomach condition that affects medication absorption.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 30 days after completion of study treatment

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 30 days after completion of study treatment

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 30 days after completion of study treatment for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Radiographic response rate

Secondary study objectives

Incidence of adverse events

Side effects data

From 2019 Phase 3 trial • 392 Patients • NCT01321554

70%

Diarrhoea

69%

Hypertension

57%

Decreased appetite

54%

Weight decreased

49%

Nausea

44%

Fatigue

40%

Headache

38%

Proteinuria

38%

Vomiting

38%

Stomatitis

33%

Palmar-plantar erythrodysaesthesia syndrome

33%

Arthralgia

33%

Dysphonia

32%

Constipation

30%

Cough

26%

Asthenia

25%

Oedema peripheral

21%

Rash

20%

Back pain

20%

Myalgia

19%

Abdominal pain

18%

Dysgeusia

18%

Abdominal pain upper

18%

Pain in extremity

18%

Musculoskeletal pain

18%

Dry mouth

18%

Dyspnoea

17%

Dizziness

16%

Pyrexia

16%

Oropharyngeal pain

16%

Hypokalaemia

15%

Dyspepsia

15%

Hypocalcaemia

14%

Epistaxis

13%

Dysphagia

13%

Alopecia

12%

Anaemia

12%

Musculoskeletal chest pain

12%

Dry skin

11%

Urinary tract infection

11%

Nasopharyngitis

10%

Oral pain

10%

Thrombocytopenia

10%

Hypoalbuminaemia

10%

Blood creatinine increased

10%

Electrocardiogram QT prolonged

10%

Upper respiratory tract infection

Dehydration

Neck pain

Depression

Hypomagnesaemia

Influenza like illness

Muscle spasms

Lymphopenia

Alanine aminotransferase increased

Muscular weakness

Malaise

Haematuria

Ejection fraction decreased

Pruritus

Hyponatraemia

Blood thyroid stimulating hormone increased

Platelet count decreased

Aspartate aminotransferase increased

Toothache

Glossodynia

Blood alkaline phosphatase increased

Hyperkeratosis

Bronchitis

Flatulence

Influenza

Dysuria

Anxiety

Hyperglycaemia

Leukopenia

Non-cardiac chest pain

Productive cough

Paraesthesia

Hypothyroidism

Haemoptysis

White blood cell count decreased

Pneumonia

General physical health deterioration

Malignant pleural effusion

Sepsis

Cholecystitis

Pulmonary embolism

seizure

Acute myocardial infarction

Atrial fibrillation

Lower respiratory tract infection

Hypotension

Lung infection

Spinal cord compression

Acute kidney injury

Blood uric acid increased

Intracranial tumour haemorrhage

Monoparesis

Acute respiratory failure

Hypercalcaemia

Hepatic failure

Appendicitis

Death

Respiratory failure

Osteoarthritis

Intestinal obstruction

Small intestinal obstruction

Acute coronary syndrome

Colitis

Transient ischaemic attack

Pancreatitis

Atrial flutter

Cardio-respiratory arrest

Uterine prolapse

Coronary artery stenosis

Pneumatosis intestinalis

Cerebrovascular accident

Confusional state

Liver injury

Diverticulitis

Bacteraemia

Gastroenteritis

Perineal abscess

Wound infection

Malignant neoplasm progression

Bone pain

Cancer pain

Syncope

Vocal cord paralysis

Nephrotic syndrome

100%

80%

60%

40%

20%

Study treatment Arm

Randomization Phase: Lenvatinib 24 mg

Randomization Phase: Placebo

OOL, Treatment Period: Lenvatinib 24 mg

OOL, Treatment Period: Lenvatinib 20 mg

Awards & Highlights

Approved for 10 Other Conditions

This treatment demonstrated efficacy for 10 other conditions.

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

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: Treatment (lenvatinib, everolimus)Experimental Treatment2 Interventions

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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Everolimus

FDA approved

Lenvatinib

FDA approved

0 / 20Eligibility 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

Carcinoid Tumor treatments often involve Receptor Tyrosine Kinase Inhibitors (RTKIs) like lenvatinib and mTOR inhibitors like everolimus. RTKIs work by blocking the activity of enzymes called tyrosine kinases, which are involved in the signaling pathways that promote tumor cell growth and angiogenesis (formation of new blood vessels). By inhibiting these pathways, RTKIs can reduce tumor growth and spread. mTOR inhibitors, on the other hand, target the mTOR pathway, which is crucial for cell growth, proliferation, and survival. Inhibiting mTOR can lead to reduced tumor cell proliferation and increased cell death. These mechanisms are particularly important for Carcinoid Tumor patients as they offer targeted approaches to slow down or stop tumor progression, potentially improving survival and quality of life.

Therapeutic strategies for patients with neuroendocrine neoplasms: current perspectives.