An Open-Label Phase 1b Study of E7386 in CombinationWith Other Anticancer Drug(s) in Subjects With SolidTumors
- Conditions
- Hepatocellular carcinoma (HCC), Solid tumor (ST), Colorectal cancer (CRC), Endometrial cancer(EC)
- Registration Number
- JPRN-jRCT2080224780
- Lead Sponsor
- Eisai Co., Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- recruiting
- Sex
- All
- Target Recruitment
- 181
1. HCC part only:
Participants with confirmed diagnosis of unresectable HCC with any of the following criteria:
a. Histologically or cytologically confirmed diagnosis of HCC, excluding fibrolamellar, sarcomatoid or mixed cholangio-HCC tumors
b. 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
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:
a. Chemotherapy and radiotherapy: 3 weeks or 5 times the half-life, whichever is shorter
b. Any antitumor therapy with antibody: 4 weeks or more
c. Any investigational drug or device: 4 weeks or more
d. 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 Part) 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
a. 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
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
1. Any of cardiac conditions as follows:
a. Heart failure New York Heart Association (NYHA) Class II or above
b. Unstable ischaemic heart disease (myocardial infarction within 6 months prior to starting study drug, or angina requiring use of nitrates more than once weekly)
c. Prolongation of QT interval with Fridericias correction (QTcF) to greater than (>) 480 millisecond (msec)
d. 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 >1 positive 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)
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
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:
Osteoporosis with T-score of < minus (-) 2.5 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
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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Safety related endpoints including DLT and/or defining the RP2D
- Secondary Outcome Measures
Name Time Method -PK profile of study drug(s)<br>-Best overall response (BOR), Objective response rate (ORR),Disease control rate (DCR), Clinical benefit rate (CBR), Progression-free survival (PFS), Overall survival, Duration of response (DOR)