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AzTrials

Endometrial NeoplasmsPhase 1/2NCT04008797

A Study of E7386 in Combination With Other Anticancer Drug(s) in Participants With Solid Tumor

A Phase 1/2 study testing E7386, Lenvatinib and Doxorubicin in people with Endometrial Neoplasms and Neoplasms, run by Eisai Inc. at 106 sites in 10 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

The primary objective of this study is to assess the safety and tolerability and to determine the recommended Phase 2 dose (RP2D) of E7386 in combination with other anticancer drug(s), and to determine the optimal dose of E7386 in combination with lenvatinib in endometrial carcinoma (EC) (for EC Dose Optimization Part… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
E7386, Lenvatinib and Doxorubicin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
301 participants
Where
106 sitesin 10 countries
Study dates
11 Jul 2019to 31 Mar 2027
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • HCC part only:
  • Participants with confirmed diagnosis of unresectable HCC with any of the following criteria:
  • Histologically or cytologically confirmed diagnosis of HCC, excluding fibrolamellar, sarcomatoid or mixed cholangio-HCC tumors
  • Clinically confirmed diagnosis of HCC according to American Association for the Study of Liver Diseases (AASLD) criteria, including cirrhosis of any etiology and/or chronic hepatitis B or C infection
  • ST part only (except for HCC):
  • Participants with histologically or cytologically confirmed diagnosis of solid tumor for which no alternative standard therapy or no effective therapy exists
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  • Life expectancy of >=12 weeks
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1
  • All AEs due to previous anti-cancer therapy have either returned to Grade 0 to 1 except for alopecia or up to Grade 2 peripheral neuropathy (renal/bone marrow/liver function should meet the inclusion criteria)
  • Adequate washout period before study drug administration:
  • Chemotherapy and radiotherapy: 3 weeks or 5 times the half-life, whichever is shorter
  • Any antitumor therapy with antibody: 4 weeks or more
  • Any investigational drug or device: 4 weeks or more
  • Blood/platelet transfusion or granulocyte colony-stimulating factor (G-CSF): 2 weeks or more Note: Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not had radiation pneumonitis
  • Adequate controlled blood pressure (BP), renal function, bone marrow function, liver function, and serum mineral level
  • At least one measurable lesion based on mRECIST (for HCC Subparts in Dose Escalation Part) or on RECIST 1.1 (for Other ST Subparts in Dose Escalation Part and all subparts in Expansion and Dose Optimization Parts) meeting following criteria
  • At least 1 lesion of >=1.0 centimeter (cm) in the longest diameter for a non-lymph node or >=1.5 cm in the short-axis diameter for a lymph node that is serially measurable according to RECIST 1.1 using computerized tomography (CT)/magnetic resonance imaging (MRI)
  • Lesions that have had external beam radiotherapy or loco-regional therapies such as radiofrequency ablation, or transarterial chemoembolisation (TACE)/ transarterial embolization (TAE) must show evidence of progressive disease based on RECIST 1.1 to be deemed a target lesion
  • For HCC participants only: Child-Pugh score A. Note: If Child-Pugh score 7 or more was observed during Screening or Baseline, the participant is ineligible and re-assessment of the Child-Pugh score is not permitted
  • For HCC participants only: Participants categorized to stage B (not amenable to locoregional therapy or refractory to locoregional therapy, and not amenable to a curative treatment), or stage C based on Barcelona Clinic Liver Cancer (BCLC) staging system
  • For HCC Subpart in Expansion Part only: prior systemic therapy for locally advanced or metastatic disease is as defined below
  • Participants who have received only one prior line of immuno oncology (IO) based regimen and have progressed on or after prior treatment with IO based regimen, or IO ineligible participants who have received no prior systemic therapy. Participants who previously received lenvatinib treatment are ineligible
  • For CRC Subpart in Expansion Part only: participants must have received at least 2 prior regimens (not exceeding 4 prior regimens) or could not tolerate standard treatment and must have received the following prior therapies in the metastatic setting if approved and locally available (progressed on at least 1 prior regimen in the metastatic setting or could not tolerate standard treatment):
  • Note: Adjuvant chemotherapy counts as prior systemic treatment if there is documented disease progression within 6 months of treatment completion Note: If a participant is determined to be intolerant to prior standard treatment, the participant must have received at least of 2 cycles of that therapy Note: Participants who have received oral tyrosine kinase inhibitor (example, regorafenib) are ineligible
  • Fluoropyrimidine, irinotecan and oxaliplatin with or without an anti-Vascular endothelial growth factor (VEGF) monoclonal antibody (mAb) (example, bevacizumab) Note: Capecitabine is acceptable as equivalent to fluoropyrimidine in prior treatment Note: Participants who have previously received fluoropyrimidine, oxaliplatin, and irinotecan as part of the same and only chemotherapy regimen, example, FOLFOXIRI or FOLFIRINOX, may be eligible after discussion with the Sponsor
  • Chemotherapy with anti- epidermal growth factor receptor (EGFR) mAb (cetuximab or panitumumab) for participants with rat sarcoma virus (RAS) (Kirsten rat sarcoma viral oncogene homolog [KRAS)/ NRAS]) wild type (WT) CRC Note: RAS (KRAS/NRAS) WT participants with right or left CRC lesions who may have not been treated with anti-EGFR mAb based on local guidelines are eligible
  • BRAF inhibitor (in combination with cetuximab ± binimetinib) for BRAF V600E mutated tumors
  • Immune checkpoint inhibitor for participants with microsatellite instability-high (MSI-H) CRC
  • For EC Subpart in Expansion Part only: Participants must have EC that has progressed after prior platinum-based chemotherapy and an anti-programmed cell death (ligand) 1 (PD-[L])1)-directed therapy for EC (participants ineligible for IO therapy who have progressed after prior platinum-based chemotherapy are eligible). Up to 3 prior systemic therapies, of which up to 2 for metastatic or locally advanced disease, are permitted Note: There is no restriction regarding prior hormonal therapies For Dose Optimization Part only: Participants must have EC that has progressed after prior platinum-based chemotherapy and an anti-PD-(L)1-directed therapy for EC. Up to 3 lines of prior therapy, regardless of setting, are allowed. Participants must be eligible for treatment with either single-agent paclitaxel or single-agent doxorubicin as determined by the investigator, with consideration of previous therapies received for EC. Note: Prior hormonal therapy and radiation are allowed and do not count as prior lines of therapy.

Who cannot join

  • Any of cardiac conditions as follows:
  • Heart failure New York Heart Association (NYHA) Class II or above
  • Prolongation of QT interval with Fridericias correction (QTcF) to greater than (>) 480 millisecond (msec)
  • Left ventricular ejection fraction (LVEF) less than (<) 50 percent (%)
  • Major surgery within 21 days or minor surgery (that is, simple excision) within 7 days prior to starting study drug. Participant must have recovered from the surgery related toxicities to less than Grade 2 Note: Adequate wound healing after major surgery must be assessed clinically, independent of time elapsed for eligibility
  • Known to be human immunodeficiency virus (HIV) positive Note: the sponsor has evaluated whether to include participant with HIV. Given that this is the first combination study of E7386 with lenvatinib and that the main mechanism of action of E7386 is immunomodulation of the tumor microenvironment along with the fact that several anti-retroviral therapies have drug-drug interaction with cytochrome P450 3A (CYP3A) substrates, the sponsor has decided not to include these participants at the current time. However, further considerations will be made moving forward based on new emerging data Note: HIV testing is required at screening only when mandated by local health authority
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  • Participants with proteinuria on urine dipstick testing will undergo 24-hour urine collection for quantitative assessment of proteinuria. Participants with urine protein >=1 gram per 24 hour will be ineligible
  • Active infection requiring systemic treatment (Except for Hepatitis B and/or C [HBV/HCV] infection in HCC participants)
  • In case of HBsAg (+) participants in HCC participants:
  • Antiviral therapy for HBV is not ongoing
  • HBV viral load is 2000 international unit per milliliter (IU/mL) or more at the Screening Period although antiviral therapy for HBV is ongoing
  • Has dual active HBV infection (HBsAg (+) and/or detectable HBV deoxyribonucleic acid [DNA]) and HCV infection (anti-HCV Ab (+) and detectable HCV ribonucleic acid [RNA]) at study entry
  • Diagnosed with meningeal carcinomatosis
  • Participants with central nervous system metastases are only eligible if they have been previously treated and are radiologically stable, (that is, without evidence of progression for at least 4 weeks prior to first dose of study treatment by repeat imaging), clinically stable, and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment
  • Pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring active treatment, including the use of oxygen
  • Any of bone disease/conditions as follows:
  • T-score of < minus (-) 3.0 at the left or right total hip, left or right femoral neck or lumbar spine (L1-L4) as determined by dual energy x-ray absorptiometry (DXA) scan. Participants with T-score <-2.5 to -3.0 can only be included if treatment with a bisphosphonate (example, zoledronic acid) or denosumab has been started at least 14 days and no more than 6 months prior to the first dose of study drug
  • Metabolic bone disease, such as hyperparathyroidism, Paget's disease or osteomalacia
  • Symptomatic hypercalcemia requiring bisphosphonate therapy
  • History of any fracture within 6 months prior to starting study drug
  • Bone metastasis requiring orthopedic intervention
  • Bone metastasis not being treated by bisphosphonate or denosumab. Participants may be included if treatment with bisphosphonate or denosumab has been started at least 14 days prior to the first dose of study drug. Participants with previous solitary bone lesions controlled with radiotherapy are eligible
  • History of symptomatic vertebral fragility fracture or any fragility fracture of the hip, pelvis, wrist or other location (defined as any fracture without a history of trauma or because of a fall from standing height or less)
  • Moderate (25% to 40% decrease in the height of any vertebrae) or severe (>40% decrease in the height of any vertebrae) morphometric vertebral fracture at baseline
  • History of malignancy (except for original disease, or definitively treated melanoma in-situ, basal or squamous cell carcinoma of the skin, carcinoma in-situ [example, bladder or cervix]) within the past 24 months prior to the first dose of study drug
  • For HCC Subpart in Dose Escalation Part only: Participants who experienced discontinuation of lenvatinib, 2 or more dose reductions of lenvatinib required from initial dose level of this study due to its toxicity, or participants who experienced single dose reduction or consecutive >=8 days dose interruption of lenvatinib within 60 days from the first dose, due to its toxicity. HCC Subpart in Expansion Part only: Participants who previously received lenvatinib treatment are ineligible.
  • EC Subpart in Expansion Part only: Participants previously treated with lenvatinib who experienced discontinuation of lenvatinib due to toxicity, or dose reduction to less than 10 mg of lenvatinib due to toxicity within 60 days from the first dose.
  • EC Dose Optimization Part only: Participants who previously received lenvatinib treatment are ineligible.
  • Bleeding or thrombotic disorders or use of anticoagulants requiring therapeutic International Normalized Ratio (INR) monitoring for HCC participants only (example, warfarin or similar agents). Treatment with low molecular weight heparin and factor X inhibitors is permitted. Treatment with antiplatelet agents is prohibited for HCC participants in Dose Escalation Part only
  • Gastrointestinal bleeding event or active hemoptysis (bright red blood of at least 0.5 teaspoon) within 3 weeks prior to the first dose of study drug
  • For HCC participants only: History of hepatic encephalopathy within 6 months prior to starting study drug
  • For EC Subpart in Expansion and Dose Optimization Parts only: carcinosarcoma (malignant mixed Mullerian tumor), endometrial leiomyosarcoma, and endometrial stromal sarcomas
  • Has preexisting >=Grade 3 gastrointestinal or non-gastrointestinal fistula
  • Evidence of current Coronavirus disease 2019 (COVID-19) infection or ongoing unrecovered active sequelae of COVID-19 infection
  • Males who have not had a successful vasectomy (confirmed azoospermia) if their female partners meet the exclusion criteria above (that is, the female partners are of childbearing potential and are not willing to use a highly effective contraceptive method throughout the study period and after study drug discontinuation). No sperm donation is allowed during the study period and after study drug discontinuation
  • Has a known psychiatric or substance abuse disorder that would interfere with the participant ability to cooperate with the requirements of the study
  • Evidence of clinically significant disease (example, cardiac, respiratory, gastrointestinal, renal disease) that in the opinion of the investigator could affect the participant safety or interfere with the study assessments
  • Scheduled for major surgery during the study

Trial locations and contacts

106 sites in 10 countries.

106 sites in 10 countries

United States28 sites

  • University of Colorado Cancer Center - Anschutz Medical Campus

    Aurora, Colorado, 80045

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • MetroHealth Medical Center

    Cleveland, Ohio, 44109

  • Women's Cancer Care - Covington, LA

    Covington, Louisiana, 70433

  • Mary Crowley Cancer Research

    Dallas, Texas, 75230

  • University of Texas Southwestern Medical

    Dallas, Texas, 75390

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • University Of Mississippi Medical Center

    Jackson, Mississippi, 39216

  • Kansas City Research Institute

    Kansas City, Missouri, 64131

  • University of California San Diego (UCSD) - Moores Cancer Center(All)

    La Jolla, California, 92037

  • UAMS

    Little Rock, Arkansas, 72205-7199

  • Cedars-Sinai Medical Center

    Los Angeles, California, 90048

  • Uni. Of Miami- Sylvester Cancer Centre

    Miami, Florida, 33136

  • Tennessee Oncology

    Nashville, Tennessee, 37203

  • Vanderbilt University Medical Center (VUMC) - Vanderbilt-Ingram Cancer Center (VICC) - Nashville

    Nashville, Tennessee, 37232

  • Perlmutter Cancer Center- NYU Langone Health

    New York, New York, 10016

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • University of Oklahoma Health Science Center

    Oklahoma City, Oklahoma, 73104

  • Pasadena Liver Center

    Pasadena, California, 91105

  • California Pacific Medical Center

    San Francisco, California, 94066

  • UCLA University of California - Los Angeles

    Santa Monica, California, 90404

  • Florida Cancer Specialists - South

    Sarasota, Florida, 34236

  • Fred Hutchinson/University of Washington Cancer Consortium

    Seattle, Washington, 98109

  • Sanford Cancer Centre

    Sioux Falls, South Dakota, 57106

  • ProMedica Flower Hospital

    Sylvania, Ohio, 43560

  • Montefiore Medical Center (MMC) - Jack D. Weiler Hospital

    The Bronx, New York, 10461

  • John Muir Clinical Research

    Walnut Creek, California, 94598

  • Florida Cancer Specialists - East

    West Palm Beach, Florida, 33401

Other trials in United States

France22 sites

  • CHU Amiens-Picardie (Hopital Sud)

    Amiens, 80000

  • CHU Bordeaux

    Bordeaux, 33075

  • CHU Cavale Blanche

    Brest, 29200

  • Centre François Baclesse

    Caen, 14000

  • Centre Jean Perrin

    Clermont-Ferrand, 63000

  • Hôpital Beaujon

    Clichy, 92110

  • Centre Georges-François Leclerc

    Dijon, 21000

  • Grenoble University Hospital (Centre Hospitalier Universitaire Grenoble Alpes)

    La Tronche, 38700

  • CHU de LILLE - Hôpital HURIEZ

    Lille, 59037

  • Hepatology, Hopital de la Croix-Rousse - 103 grande rue de la Croix-Rousse

    Lyon, 69004

  • Centre Léon Bérard

    Lyon, 69008

  • Centre Antoine Lacassagne

    Nice, 6100

  • Institut Curie - Centre de Recherche

    Paris, 75005

  • APHP Hospital Saint-Antoine

    Paris, 75012

  • AP-HP Université de Paris, Port Royal

    Paris, 75014

  • Hopital Europeen Georges-Pompidou (HEGP)

    Paris, 75015

  • Hopital de la Croix Saint-Simon

    Paris, 75020

  • Centre Hospitalier Universitaire de Bordeaux (CHU Bordeaux)(Hopitaux de Bordeaux) - Groupe hospitalier Sud - Hopital Haut-Levequ

    Pessac, 33604

  • Centre Hospitalier Universitaire (CHU) de Poitiers

    Poitiers, 86000

  • Insitute de Cancérologie de l'Ouest - Centre René Gauducheau

    Saint-Herblain, 44800

  • ICANs

    Strasbourg, 67200

  • Gustave Roussy Institute (IGR)

    Villejuif, 94805

Other trials in France

Japan15 sites

  • Eisai#1013

    Akashi, Hyōgo

  • Eisai#1004

    Chiba

  • Eisai#1001

    Chuo-ku, Tokyo

  • Eisai#1009

    Hidaka, Saitama

  • Eisai#1012

    Kamigyō-ku, Kyoto

  • Eisai#1002

    Kashiwa, Chiba

  • Eisai#1010

    Kawasaki, Kanagawa

  • Eisai#1006

    Koto-ku, Tokyo

  • Eisai#1007

    Kurume, Fukuoka

  • Eisai#1008

    Matsuyama, Ehime

  • Eisai#1015

    Minato-ku, Tokyo

  • Eisai#1005

    Nagoya, Aichi-ken

  • Eisai#1014

    Niigata

  • Eisai#1003

    Sayama, Osaka

  • Eisai#1011

    Toyoake, Aichi-ken

Other trials in Japan

China13 sites

  • Beijing Cancer Hospital

    Beijing, 100142

  • Peking Union Medical College Hospital

    Beijing, 100730

  • The First Bethune Hospital of Jilin University

    Changchun, 130021

  • Fujian Provincial Cancer Hospital

    Fuzhou, 350014

  • Sun Yan-sen University Cancer Center

    Guangzhou, 510060

  • Sun Yat-Sen Memrial Hospital, Sun Yat-Sen University

    Guangzhou, 510289

  • Cancer Hospital of Shandong First Medical University

    Jinan, 250117

  • Yunnan Cancer Hospital

    Kunming, 650118

  • Fudan University Cancer Center

    Shanghai, 200032

  • The Tenth People's Hospital; Shanghai Tongji University

    Shanghai, 200072

  • Cancer Hospital Chinese Academy of Medical Sciences, Shenzhen Center

    Shenzhen, 518100

  • Tianjin Cancer Hospital

    Tianjin, 300060

  • The First Affiliated Hospital of Wenzhou Medical University

    Wenzhou, 325000

Other trials in China

South Korea9 sites

  • Korea University Guro Hospital

    Guro-gu, 08308

  • National Cancer Center

    Ilsandong-gu, 10408

  • Seoul National University Hospital

    Jongno-gu, 03080

  • Seoul St. Mary's Hospital

    Seocho-Gu, 06591

  • Severance Hospital (Yonsei University Medical Center)

    Seodaemun, 03722

  • Seoul National University Bundang Hospital

    Seongnamsi Bundang, 13620

  • Samsung Medical Center

    Seoul, 06351

  • University of Ulsan College of Medicine - Asan Medical Center (AMC)

    Songpa-gu, 05505

  • Asan Medical Center

    Songpa-Gu, 05505

Other trials in South Korea

Spain6 sites

  • University Hospital A Coruña

    A Coruña, 15006

  • Fundació Privada Institut d'Investigació Oncològica de Vall-Hebron (VHIO)

    Barcelona, 08035

  • Hospital Universitario de Jaén

    Jaén, 23007

  • Clínica Universidad de Navarra

    Madrid, 28027

  • H. Clinico San Carlos

    Madrid, 28040

  • Hospital Universitario 12 de Octubre

    Madrid, 28041

Other trials in Spain

Taiwan6 sites

  • Chang Gung Medical Foundation - Kaohsiung Branch

    Kaohsiung City, 83301

  • Taichung Veterans General Hospital

    Taichung, 40705

  • National Cheng Kung University Hospital

    Tainan, 704

  • National Taiwan University Hospital

    Taipei, 100

  • Taipei Veterans General Hospital

    Taipei, 11217

  • Chang Gung Medical Foundation - Linkou Branch

    Taoyuan, 33305

Other trials in Taiwan

Canada3 sites

  • CHUM, Unit for Innovative Therapies

    Montreal, Quebec, H2X 0C1

  • McGill University Health Centre

    Montreal, Quebec, H4A 3J1

  • Sunnybrook Research Institute

    Toronto, Ontario, M4N 3M5

Other trials in Canada

Italy3 sites

  • Clinica Oncologica AOU (Azienda Ospedaliero Universitaria) delle Marche

    Ancona, 60126

  • Istituto Clinico Humanitas, Rozzano

    Milan, 20159

  • Fondazione Policlinico Gemelli IRCCS

    Rome, 00168

Other trials in Italy

Denmark1 site

  • Odense University Hospital

    Odense, 5000

Other trials in Denmark

About this study

Official title: An Open-label Study of E7386 in Combination With Other Anticancer Drug(s) in Subjects With Solid Tumors

The primary objective of this study is to assess the safety and tolerability and to determine the recommended Phase 2 dose (RP2D) of E7386 in combination with other anticancer drug(s), and to determine the optimal dose of E7386 in combination with lenvatinib in endometrial carcinoma (EC) (for EC Dose Optimization Part only).

Read the detailed description

The Dose Escalation and Dose Expansion parts of the study have completed enrollment. The Dose Optimization part of the study is enrolling participants with endometrial carcinoma (EC) only.

Being tested
E7386, Lenvatinib, Doxorubicin, Paclitaxel
Keywords
Endometrial cancer, Solid Tumor, Hepatocellular carcinoma, Colorectal cancer, E7386, Lenvatinib
Medical subject headings
Endometrial Neoplasms, Neoplasms, Carcinoma, Hepatocellular, Liver Neoplasms, Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT04008797
Study groupRoleWhat they receive
Dose Escalation Part: HCC: E7386 QD Subpart + LenvatinibExperimentalParticipants with hepatocellular carcinoma (HCC) will receive E7386, once daily (QD) for 5 or 6 consecutive days followed by a period of time without treatment in Cycle 0 (6 or 7 days). Participants with HCC will receive E7386, QD in combination with lenvatinib 8 milligram (mg) (participants with body weight of less than [<] 60 kilograms [kg]) or 12 mg (participants with body weight >=60 kg), capsules, orally, QD in 28-day treatment cycles until PD, development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or termination of the study program.
Receives: Drug: E7386; Drug: Lenvatinib
Dose Escalation Part: HCC: E7386 BID Subpart + LenvatinibExperimentalParticipants with HCC will receive E7386, twice daily (BID) for 5 or 6 consecutive days in Cycle 0 (6 or 7 days). Participants with HCC will receive E7386, BID in combination with lenvatinib 8 mg (participants with body weight of < 60 kg) or 12 mg (participants with body weight >=60 kg) capsules, orally, QD in 28-day treatment cycles until PD, development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or termination of the study program.
Receives: Drug: E7386; Drug: Lenvatinib
Dose Escalation Part: Other ST: E7386 QD Subpart + LenvatinibExperimentalParticipants with solid tumor (ST) (except for HCC) will receive E7386, QD for 5 or 6 consecutive days followed by a period of time without treatment in Cycle 0 (6 or 7 days). Participants with ST (except for HCC) will receive E7386, QD in combination with lenvatinib 20 mg, capsules, orally, QD in 28-day treatment cycles until PD, development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or termination of the study program.
Receives: Drug: E7386; Drug: Lenvatinib
Dose Escalation Part: Other ST: E7386 BID Subpart + LenvatinibExperimentalParticipants with ST (except for HCC) will receive E7386, BID for 5 or 6 consecutive days in Cycle 0 (6 or 7 days). Participants with ST (except for HCC) will receive E7386, BID in combination with lenvatinib 20 mg, capsules, orally, QD in 28-day treatment cycles until PD, development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or termination of the study program.
Receives: Drug: E7386; Drug: Lenvatinib
Dose Expansion Part: HCC Subpart: Lenvatinib OnlyExperimentalParticipants with HCC will receive lenvatinib 8 mg (participants with body weight of <60 kg) or 12 mg (participants with body weight >=60 kg), capsules, orally, QD in 28-day treatment cycles until PD, development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or termination of the study program
Receives: Drug: Lenvatinib
Dose Expansion Part: HCC Subpart: E7386 + LenvatinibExperimentalParticipants with HCC will receive lenvatinib 8 mg (participants with body weight of <60 kg) or 12 mg (participants with body weight >=60 kg), capsule, orally QD in combination with E7386 y, BID in 28-day treatment cycles until PD, development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or termination of the study program.
Receives: Drug: E7386; Drug: Lenvatinib
Dose Expansion Part: CRC Subpart: E7386 + LenvatinibExperimentalParticipants with colorectal cancer (CRC) will receive E7386, BID in combination with lenvatinib 20 mg, capsules, orally, QD in 28-day treatment cycles until PD, development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or termination of the study program.
Receives: Drug: E7386; Drug: Lenvatinib
Dose Expansion Part: EC Subpart: E7386 + LenvatinibExperimentalParticipants with endometrial cancer (EC) will receive E7386, BID in combination with lenvatinib 14 mg, capsules, orally, QD in 28-day treatment cycles until PD, development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or termination of the study program.
Receives: Drug: E7386; Drug: Lenvatinib
Dose Optimization Part: EC ParticipantsExperimentalParticipants with EC will be randomized to receive 2 different doses of E7386 in combination with lenvatinib capsule or lenvatinib capsule monotherapy in 28-days cycles, or treatment of physician's choice (TPC; doxorubicin in 21-day cycles or paclitaxel in 28-day cycles [3 weeks on/1 week off]), until PD, development of unacceptable toxicity, participant request to discontinue, withdrawal of consent, or termination of the study program.
Receives: Drug: E7386; Drug: Lenvatinib; Drug: Doxorubicin; Drug: Paclitaxel

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose Escalation Part: Number of Participants with Dose-limiting Toxicities (DLTs)

    DLTs will be defined as any of the events that are considered by the investigator to be at least possibly related to therapy with the study medication. Toxicity will be evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE 5.0).

    Measured: Cycle 0 (Cycle 0 length=6 or 7 days) up to Cycle 1 (Cycle 1 length=28 days)

  2. Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs)

    Measured: Up to 30 days after the last dose of study drug or before initiating post anti-cancer treatment (up to approximately 90 months)

  3. Dose Optimization Part: Objective Response Rate (ORR) per RECIST 1.1 by Investigator Assessment

    The ORR is defined as the percentage of participants with a best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR). The ORR will be assessed by investigator based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 for dose optimization part.

    Measured: From first dose of study drug until PD, development of unacceptable toxicity, participant requests to discontinue, withdrawal of consent or study termination (up to approximately 90 months)

Secondary outcomes (17)

  1. Dose Escalation Part: Cmax: Maximum Observed Plasma Concentration for E7386

    Measured: Day 1 to Day 8

  2. Dose Escalation Part: Cmax: Maximum Observed Plasma Concentration for Lenvatinib

    Measured: Day 8

  3. Dose Escalation Part: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for E7386

    Measured: Day 1 to Day 8

  4. Dose Escalation Part: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Lenvatinib

    Measured: Day 8

  5. Dose Escalation Part: AUC: Area Under the Plasma Concentration Versus Time Curve for E7386

    Measured: Day 1 to Day 8

  6. Dose Escalation Part: AUC: Area Under the Plasma Concentration Versus Time Curve for Lenvatinib

    Measured: Day 8

  7. Dose Escalation Part: CL/F: Apparent Total Body Clearance for E7386

    Measured: Day 1 to Day 8

  8. Dose Escalation Part: CL/F: Apparent Total Body Clearance for Lenvatinib

    Measured: Day 8

  9. Dose Escalation Part: Vz/F: Apparent Volume of Distribution for E7386

    Measured: Day 1 to Day 8

  10. Dose Escalation Part: Vz/F: Apparent Volume of Distribution for Lenvatinib

    Measured: Day 8

  11. Percentage of Participants with Best Overall Response (BOR)

    BOR is defined as confirmed CR, confirmed PR, stable disease (SD), PD, and not evaluable (NE). The BOR will be assessed by investigator based on Modified Response Evaluation Criteria in Solid Tumors (mRECIST) for HCC subparts in dose escalation part and based on RECIST version 1.1 for ST subparts in dose escalation part, and for HCC subpart, CRC subpart, EC subpart in dose expansion part and in dose optimization part.

    Measured: From first dose of study drug until progression of disease (PD), development of unacceptable toxicity, participant requests to discontinue, withdrawal of consent or study termination (up to approximately 90 months)

  12. Objective Response Rate (ORR)

    The ORR is defined as the percentage of participants with a BOR of CR or PR. The ORR will be assessed by investigator based on mRECIST for HCC subparts in dose escalation part and based on RECIST version 1.1 for ST-subparts in dose escalation part, and for HCC subpart, CRC subpart, EC subpart in dose expansion part.

    Measured: From first dose of study drug until PD, development of unacceptable toxicity, participant requests to discontinue, withdrawal of consent or study termination (up to approximately 90 months)

  13. Disease Control Rate (DCR)

    DCR is defined as the percentage of participants with a BOR of CR, PR, or SD. The DCR will be assessed by investigator based on mRECIST for HCC subparts in dose escalation part and based on RECIST version 1.1 for ST-subparts in dose escalation part, and for HCC subpart, CRC subpart, EC subpart in dose expansion part and in dose optimization part.

    Measured: From first dose of study drug until PD, development of unacceptable toxicity, participant requests to discontinue, withdrawal of consent or study termination (up to approximately 90 months)

  14. Clinical Benefit Rate (CBR)

    The CBR is defined as the percentage of participants with a BOR of CR, PR, or durable SD. The CBR will be assessed by investigator based on mRECIST for HCC subparts in dose escalation part and based on RECIST version 1.1 for ST-subparts in dose escalation part, and for HCC subpart, CRC subpart, EC subpart in dose expansion part and in dose optimization part.

    Measured: From first dose of study drug until PD, development of unacceptable toxicity, participant requests to discontinue, withdrawal of consent or study termination (up to approximately 90 months)

  15. Progression-free Survival (PFS)

    PFS is defined as the time from the date of the first dose to the date of the first documentation of confirmed PD or death, whichever occurs first. The PFS will be assessed by investigator based on mRECIST for HCC subparts in dose escalation part and based on RECIST version 1.1 for ST-subparts in dose escalation part, and for HCC subpart, CRC subpart, EC subpart in dose expansion part and in dose optimization part.

    Measured: From first dose of study drug until PD, or death from any cause, whichever occurs first (up to approximately 90 months)

  16. Overall Survival (OS)

    OS is defined as the time from the first dose of study drug to death due to any cause. OS will be calculated for all subparts in dose expansion part, dose optimization part, and HCC subparts in dose escalation part only.

    Measured: From first dose of study drug until death from any cause (up to approximately 90 months)

  17. Duration of Response (DOR)

    DOR is defined as the time from the first documentation of PR or CR to the first documentation of disease progression or death due to any cause (whichever occurs first). DOR will be calculated for all subparts in dose expansion part, dose optimization part, and HCC subparts in dose escalation part only.

    Measured: From first dose of study drug until PD, or death from any cause, whichever occurs first (up to approximately 90 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Jul 2019
  2. Study start11 Jul 2019
  3. Primary completion31 Mar 2027 (estimated)
  4. Study completion31 Mar 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Model description
The Dose Optimization part and HCC subpart of Expansion part of the study are randomized. The Dose Escalation part, and CRC/EC subparts of Dose Escalation part are non-randomized.
Masking
None (open label)
Enrolment
301 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04008797
Sponsor's protocol ID
E7386-J081-102
Other IDs
2022-003300-32, 2023-510275-64-00, 2023
Status last verified
Oct 2026
First submitted
24 Jun 2019
Last updated
14 Oct 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Eisai's data sharing commitment and further information on how to request data can be found on our website http://eisaiclinicaltrials.com/.

Publications

  • Lee JY, Hasegawa K, Kim BG, Berman B, Suzuki S, Corr B, Yunokawa M, Orr D, Yamamoto N, Soliman PT, Miller DS, Potdar AA, Sahara T, Kimura T, Dutta L, Wu J, McKenzie J, Kyi C. E7386 plus lenvatinib in patients with advanced endometrial cancer that progressed on platinum-based chemotherapy and an anti-PD-(L)1 immunotherapy: a single-arm, open-label, global phase 1b/2 dose-expansion cohort. EClinicalMedicine. 2026 Sep 23;100:104206. doi: 10.1016/j.eclinm.2026.104206. eCollection 2026 Oct.

    PubMed 42830785

  • Mesropian A, Gris-Oliver A, Balaseviciute U, Potdar AA, Kimura T, Shen J, Torres-Marcen M, Abril-Fornaguera J, Pique-Gili M, Camell-Raventos D, Peix J, Fernandez-Martinez E, Huguet-Pradell J, Hernandez de Sande A, Keraite I, Esteban-Fabro R, Barcena-Varela M, Lindblad KE, Lujambio A, Guccione E, Thung S, Ikeda M, Kudo M, Sia D, Pinyol R, Llovet JM. E7386 Enhances Lenvatinib's Antitumor Activity in Preclinical Models and Human Hepatocellular Carcinoma. Clin Cancer Res. 2025 Dec 1;31(23):5037-5050. doi: 10.1158/1078-0432.CCR-25-0725.

    PubMed 40986544

  • Eskander RN, Lee JY, Mirza MR, Lorusso D, MacKay H, Ray-Coquard I, Oaknin A, Gonzalez-Martin A, Hasegawa K, Corr BR, Wu X, Leary A, Hu T, Dutta L, Okpara CE, McKenzie J, Makker V. Randomized study evaluating optimal dose, efficacy, and safety of E7386 plus lenvatinib versus treatment of physician's choice in advanced/recurrent endometrial carcinoma previously treated with platinum-based chemotherapy and immune checkpoint inhibitors. Int J Gynecol Cancer. 2025 Sep;35(9):101812. doi: 10.1016/j.ijgc.2025.101812. Epub 2025 Apr 5.

    PubMed 40318924

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing E7386, Lenvatinib and Doxorubicin in people with Endometrial Neoplasms and Neoplasms, run by Eisai Inc. at 106 sites in 10 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 29 inclusion and 38 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 14 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 106 sites in United States, France, Japan, China, South Korea and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose Escalation Part: Number of Participants with Dose-limiting Toxicities (DLTs) (time frame: Cycle 0 (Cycle 0 length=6 or 7 days) up to Cycle 1 (Cycle 1 length=28 days)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04008797, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Oct 2026.

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