RECRUITING

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

Conditions

Neoplasms Carcinoma, Hepatocellular Liver Neoplasms Colorectal Neoplasms Endometrial Neoplasms Solid Tumor Hepatocellular carcinoma Endometrial cancer Colorectal cancer E7386 Lenvatinib

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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).

Official Title

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

Quick Facts

Study Start:2019-07-11

Study Completion:2026-11-30

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04008797

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. HCC part only: 1. Histologically or cytologically confirmed diagnosis of HCC, excluding fibrolamellar, sarcomatoid or mixed cholangio-HCC tumors 2. 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 2. Life expectancy of \>=12 weeks 3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1 4. 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) 5. Adequate washout period before study drug administration: 1. Chemotherapy and radiotherapy: 3 weeks or 5 times the half-life, whichever is shorter 2. Any antitumor therapy with antibody: 4 weeks or more 3. Any investigational drug or device: 4 weeks or more 4. 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 6. Adequate controlled blood pressure (BP), renal function, bone marrow function, liver function, and serum mineral level 7. 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 8. 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 9. 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 10. For HCC Subpart in Expansion Part only: prior systemic therapy for locally advanced or metastatic disease is as defined below 11. 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): 1. 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 2. 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 3. BRAF inhibitor (in combination with cetuximab ± binimetinib) for BRAF V600E mutated tumors 4. Immune checkpoint inhibitor for participants with microsatellite instability-high (MSI-H) CRC 12. 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. Note: Prior hormonal therapy and radiation are allowed and do not count as prior lines of therapy.	1. 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 (%) 2. 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 3. 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 4. 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 5. Active infection requiring systemic treatment (Except for Hepatitis B and/or C \[HBV/HCV\] infection 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 6. Diagnosed with meningeal carcinomatosis 7. 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 8. Pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring active treatment, including the use of oxygen 9. 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 10. 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 11. 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. 12. 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 13. 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 14. For HCC participants only: History of hepatic encephalopathy within 6 months prior to starting study drug 15. For EC Subpart in Expansion and Dose Optimization Parts only: carcinosarcoma (malignant mixed Mullerian tumor), endometrial leiomyosarcoma, and endometrial stromal sarcomas 16. Has preexisting \>=Grade 3 gastrointestinal or non-gastrointestinal fistula 17. Evidence of current Coronavirus disease 2019 (COVID-19) infection or ongoing unrecovered active sequelae of COVID-19 infection 18. 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 19. Has a known psychiatric or substance abuse disorder that would interfere with the participant ability to cooperate with the requirements of the study 20. 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 21. Scheduled for major surgery during the study

Inclusion Criteria

Exclusion Criteria

1. HCC part only:
1. Histologically or cytologically confirmed diagnosis of HCC, excluding fibrolamellar, sarcomatoid or mixed cholangio-HCC tumors
2. 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
2. Life expectancy of \>=12 weeks
3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1
4. 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)
5. Adequate washout period before study drug administration:
1. Chemotherapy and radiotherapy: 3 weeks or 5 times the half-life, whichever is shorter
2. Any antitumor therapy with antibody: 4 weeks or more
3. Any investigational drug or device: 4 weeks or more
4. 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
6. Adequate controlled blood pressure (BP), renal function, bone marrow function, liver function, and serum mineral level
7. 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
8. 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
9. 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
10. For HCC Subpart in Expansion Part only: prior systemic therapy for locally advanced or metastatic disease is as defined below
11. 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):
1. 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
2. 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
3. BRAF inhibitor (in combination with cetuximab ± binimetinib) for BRAF V600E mutated tumors
4. Immune checkpoint inhibitor for participants with microsatellite instability-high (MSI-H) CRC
12. 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. Note: Prior hormonal therapy and radiation are allowed and do not count as prior lines of therapy.

1. 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 (%)
2. 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
3. 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
4. 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
5. Active infection requiring systemic treatment (Except for Hepatitis B and/or C \[HBV/HCV\] infection 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
6. Diagnosed with meningeal carcinomatosis
7. 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
8. Pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring active treatment, including the use of oxygen
9. 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
10. 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
11. 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.
12. 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
13. 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
14. For HCC participants only: History of hepatic encephalopathy within 6 months prior to starting study drug
15. For EC Subpart in Expansion and Dose Optimization Parts only: carcinosarcoma (malignant mixed Mullerian tumor), endometrial leiomyosarcoma, and endometrial stromal sarcomas
16. Has preexisting \>=Grade 3 gastrointestinal or non-gastrointestinal fistula
17. Evidence of current Coronavirus disease 2019 (COVID-19) infection or ongoing unrecovered active sequelae of COVID-19 infection
18. 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
19. Has a known psychiatric or substance abuse disorder that would interfere with the participant ability to cooperate with the requirements of the study
20. 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
21. Scheduled for major surgery during the study

Contacts and Locations

Study Contact

Eisai Inquiry Service

CONTACT

eisai-chiken_hotline@hhc.eisai.co.jp

Study Locations (Sites)

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

La Jolla, California, 92037

United States

Cedars-Sinai Medical Center

Los Angeles, California, 90048

United States

Pasadena Liver Center

Pasadena, California, 91105

United States

UCLA University of California - Los Angeles

Santa Monica, California, 90404

United States

University of Colorado Cancer Center - Anschutz Medical Campus

Aurora, Colorado, 80045

United States

Florida Cancer Specialists - South

Sarasota, Florida, 34236

United States

Florida Cancer Specialists - East

West Palm Beach, Florida, 33401

United States

Kansas City Research Institute

Kansas City, Missouri, 64131

United States

Perlmutter Cancer Center- NYU Langone Health

New York, New York, 10016

United States

Memorial Sloan Kettering Cancer Center

New York, New York, 10065

United States

University of Oklahoma Health Science Center

Oklahoma City, Oklahoma, 73104

United States

Medical University of South Carolina

Charleston, South Carolina, 29425

United States

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

Nashville, Tennessee, 37232

United States

Mary Crowley Cancer Research

Dallas, Texas, 75230

United States

University of Texas Southwestern Medical

Dallas, Texas, 75390

United States

MD Anderson Cancer Center

Houston, Texas, 77030

United States

Collaborators and Investigators

Sponsor: Eisai Inc.

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2019-07-11

Study Completion Date2026-11-30

Study Record Updates

Study Start Date2019-07-11

Study Completion Date2026-11-30

Terms related to this study

Keywords Provided by Researchers

Solid Tumor
Hepatocellular carcinoma
Endometrial cancer
Colorectal cancer
E7386
Lenvatinib

Additional Relevant MeSH Terms

Neoplasms
Carcinoma, Hepatocellular
Liver Neoplasms
Colorectal Neoplasms
Endometrial Neoplasms