Lenvatinib for Solid Tumors in Pediatric Patients

(E7080-G000-231 Trial)

No longer recruiting at 66 trial locations

Overseen By Toll Free Number

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Merck Sharp & Dohme Corp.

Must be taking: Antihypertensives

Disqualifiers: HIV, Hepatitis B/C, Cardiovascular disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 21 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of lenvatinib for treating various solid tumors in young people. It targets cancers that have returned or resisted other treatments, such as Ewing sarcoma, rhabdomyosarcoma, and high-grade glioma. The trial includes separate groups for each tumor type to assess lenvatinib's effectiveness for each condition. It suits young individuals with these specific relapsed or stubborn solid tumors. As a Phase 2 trial, it measures the treatment's effectiveness in an initial, smaller group, providing an opportunity to contribute to important research.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that you must have adequate blood pressure control, which can be with or without antihypertensive medications. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatment is likely to be safe?

Research has shown that lenvatinib has been tested in children with various solid tumors. In studies where lenvatinib was used alone or with other drugs, researchers found it to have manageable side effects. While side effects can occur, they can often be controlled by adjusting the dose or taking breaks from treatment. Common side effects include tiredness, loss of appetite, and high blood pressure.

For conditions like rhabdomyosarcoma and other tumors, lenvatinib at doses similar to those in this trial has been manageable for most patients. Sometimes, side effects like high blood pressure and diarrhea required reducing the dose.

In cases of high-grade glioma and Ewing sarcoma, lenvatinib was tolerated well enough to continue testing. While the drug can cause side effects, these are generally similar to those of other treatments in this category of medications.

Overall, lenvatinib's safety in children is still under study, but previous findings suggest it is generally well-tolerated with careful monitoring and management of side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for solid tumors?

Lenvatinib is unique because it targets multiple receptor tyrosine kinases involved in tumor growth, which could potentially offer a broader impact compared to traditional chemotherapies. Unlike standard treatments that often focus on a single pathway, lenvatinib's ability to inhibit several pathways simultaneously might enhance its effectiveness against resistant cancer cells. Researchers are excited about this treatment for pediatric solid tumors because it opens up new possibilities for managing cancers that have limited responses to existing therapies.

What evidence suggests that this trial's treatments could be effective for solid tumors in pediatric patients?

This trial will evaluate lenvatinib for various childhood solid tumors. Research has shown that lenvatinib may help treat these conditions, but results vary by tumor type. Participants with rhabdomyosarcoma will receive lenvatinib, which has shown potential to fight tumors when combined with another drug, though its exact effectiveness remains unclear. For those with medulloblastoma, studies suggest lenvatinib might help delay tumor growth, but its overall success is not confirmed. In high-grade gliomas and diffuse midline gliomas, few patients experienced tumor shrinkage. Similarly, lenvatinib did not significantly reduce tumors in ependymoma and other solid tumors. Overall, while lenvatinib has limited success in shrinking tumors, its safety and potential to enhance other treatments make it worth further study. ^{1 2 3 4 6}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

This trial is for children, adolescents, and young adults with certain types of solid tumors that have come back or didn't respond to treatment. They must be able to perform daily activities at a certain level, have measurable tumor growth, stable organ function including heart and kidneys, controlled blood pressure, no serious infections or HIV, not pregnant or breastfeeding (if applicable), and agree to use contraception.

Inclusion Criteria

I agree to use contraception and not donate sperm during and for 7 days after treatment.

I can do most activities, and if I have a brain tumor, my condition has been stable for at least a week.

I am not pregnant, breastfeeding, and if capable of bearing children, I agree to use contraception during and after the study.

Exclusion Criteria

My scans show cancer affecting major blood vessels or has caused holes in the tumor.

I have a severe fistula in my GI tract or elsewhere.

I am currently being treated for an infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive lenvatinib 14 mg/m^2 QD orally until progressive disease or unacceptable toxicity

Up to 21 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Lenvatinib

Trial Overview The study tests Lenvatinib's effectiveness in shrinking tumors and its safety in young patients with relapsed/refractory solid malignancies. Participants are grouped based on their specific type of cancer and will receive the drug while being monitored for response.

How Is the Trial Designed?

Group I: Rhabdomyosarcoma Experimental Treatment 1 Intervention

Participants with rhabdomyosarcoma will receive lenvatinib 14 mg/m\^2 QD orally until progressive disease or unacceptable toxicity.

Group II: Other Solid Tumors Excluding Osteosarcoma, Diffuse Midline Glioma, Medulloblastoma and Ependymoma Experimental Treatment 1 Intervention

Participants with other solid tumors will receive lenvatinib 14 mg/m\^2 QD orally until progressive disease or unacceptable toxicity.

Group III: Medulloblastoma Experimental Treatment 1 Intervention

Participants with medulloblastoma will receive lenvatinib 14 mg/m\^2 QD orally until progressive disease or unacceptable toxicity.

Group IV: High Grade Glioma Experimental Treatment 1 Intervention

Participants with high grade glioma will receive lenvatinib 14 mg/m\^2 QD orally until progressive disease or unacceptable toxicity.

Group V: Ewing Sarcoma Experimental Treatment 1 Intervention

Participants with Ewing sarcoma will receive lenvatinib 14 mg/m\^2 once daily (QD) orally until progressive disease or unacceptable toxicity.

Group VI: Ependymoma Experimental Treatment 1 Intervention

Participants with ependymoma will receive lenvatinib 14 mg/m\^2 QD orally until progressive disease or unacceptable toxicity.

Group VII: Diffuse Midline Glioma Experimental Treatment 1 Intervention

Participants with diffuse midline glioma will receive lenvatinib 14 mg/m\^2 QD orally until progressive disease or unacceptable toxicity.

Lenvatinib is already approved in United States, European Union for the following indications:

Approved in United States as Lenvima for:

• Differentiated Thyroid Cancer
• Renal Cell Carcinoma
• Hepatocellular Carcinoma
• Endometrial Cancer

Approved in European Union as Lenvima for:

• Thyroid Cancer
• Renal Cell Carcinoma
• Hepatocellular Carcinoma
• Endometrial Cancer

Approved in European Union as Kisplyx for:

• Renal Cell Carcinoma

Who Is Running the Clinical Trial?

Merck Sharp & Dohme Corp.

Lead Sponsor

Trials

2,287

Recruited

4,582,000+

Chirfi Guindo

Merck Sharp & Dohme Corp.

Chief Medical Officer

Engineering degree from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme Corp.

Chief Executive Officer since 2021

J.D. from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Merck Sharp & Dohme LLC

Lead Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Eisai Inc.

Industry Sponsor

Trials

524

Recruited

161,000+

Founded

Eisai Inc. was established in 1995 as the U.S. subsidiary of Eisai Co., Ltd.

Headquarters

Woodcliff Lake, NJ, USA

Known For

Neurology and Oncology

Top Products

Aricept (donepezil), Lenvima (lenvatinib), Leqembi (lecanemab), Halaven (eribulin)

Lynn Kramer

Eisai Inc.

Chief Medical Officer since 2019

MD

Tatsuyuki Yasuno

Eisai Inc.

Chief Executive Officer since 2023

MBA from Kellogg School of Management, Northwestern University; Bachelor of Political Science from Waseda University

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04447755

A Study of Lenvatinib (MK-7902) in Pediatric Participants ... The main purpose of this study is to evaluate the antitumor activity and safety of lenvatinib (MK-7902/E7080) in children, adolescents, and young adults ...

2. fda.gov fda.gov/media/182162/download

Lenvima (Lenvatinib) - Office of Clinical Pharmacology ... The safety and effectiveness of lenvatinib in pediatric patients has not been established. Efficacy results of Studies 216, 231, 207, and 230 do not support ...

3. trialstransparency.merckclinicaltrials.com trialstransparency.merckclinicaltrials.com/Upload/989_MK-7902-013-CSR%20Synopsis_final-redaction.pdf

lenvatinib - MSD Clinical Trials No objective responses were observed in the HGG, diffuse midline glioma, medulloblastoma, or ependymoma cohorts. The ORR at Week 16 was 7.7% (5 PRs) among all ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8477142/

Phase I/II study of single-agent lenvatinib in children and ... As evidenced by 5-year survival rates (range: 60.6% to 68.1% from 1987 to 2002), there has been minimal progress since the mid-1980s.

5. ema.europa.eu ema.europa.eu/en/documents/product-information/lenvima-epar-product-information_en.pdf

Lenvima, INN-lenvatinib - European Medicines Agency The safety and efficacy of lenvatinib in children aged 2 to <18 years have not been established. Currently available data are described in sections 4.8, 5.1, ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12002095/

Ara-C suppresses H3 K27–altered spinal cord diffuse midline ... Our study has focused on highlighting the clinical implications of Ara-C in inhibiting tumor cell growth and improving ICI treatment outcomes.