A Study of E7386 in Participants With Advanced Solid Tumor Including Colorectal Cancer (CRC)

Sponsor

Eisai Co., Ltd. (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03833700

Collaborator

(none)

Enrollment

Locations

Arms

60.9

Anticipated Duration (Months)

12.5

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary objective of this study is to assess the safety and tolerability of E7386 in participants with solid tumor including CRC.

Condition or Disease	Intervention/Treatment	Phase
Solid Neoplasms Colorectal Neoplasms Gastrointestinal Tumors	Drug: E7386	Phase 1

Detailed Description

The study will be conducted in 2 parts: dose escalation part and expansion part. The study will include Pre-treatment Phase, Treatment Phase, and Extension Phase (in expansion part only).

Eligible participants from Pre-Treatment Phase (screening period) will enter into the Treatment Phase to receive E7386. After Treatment Phase, participants will be followed in follow-up period of Extension Phase (in expansion part only).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

An Open-label Phase 1 Study of E7386 in Subjects With Advanced Solid Tumor Including Colorectal Cancer

Actual Study Start Date :

Mar 5, 2019

Anticipated Primary Completion Date :

Mar 31, 2024

Anticipated Study Completion Date :

Mar 31, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dose Escalation Part: E7386 Participants will receive E7386 10, 15, 20 mg (milligram) or more, tablets, orally, twice daily, in 28-days treatment cycle until disease progression (PD), development of unacceptable toxicity, participant's request to discontinue, withdrawal of consent, or termination of the study program. Dose escalation of E7386 will be based on the available safety data from the previous cohorts.	Drug: E7386 E7386, tablets, orally.
Experimental: Expansion Part Participants will receive E7386, tablets, orally, twice daily in 28-days treatment cycle until PD, development of unacceptable toxicity, participant's request to discontinue, withdrawal of consent, or termination of the study program. The highest dose of E7386 which is deemed tolerable or the optimal dose based on PK or PD analysis in dose escalation part will be used.	Drug: E7386 E7386, tablets, orally.

Arm

Intervention/Treatment

Experimental: Dose Escalation Part: E7386

Participants will receive E7386 10, 15, 20 mg (milligram) or more, tablets, orally, twice daily, in 28-days treatment cycle until disease progression (PD), development of unacceptable toxicity, participant's request to discontinue, withdrawal of consent, or termination of the study program. Dose escalation of E7386 will be based on the available safety data from the previous cohorts.

Drug: E7386

E7386, tablets, orally.

Experimental: Expansion Part

Participants will receive E7386, tablets, orally, twice daily in 28-days treatment cycle until PD, development of unacceptable toxicity, participant's request to discontinue, withdrawal of consent, or termination of the study program. The highest dose of E7386 which is deemed tolerable or the optimal dose based on PK or PD analysis in dose escalation part will be used.

Drug: E7386

E7386, tablets, orally.

Outcome Measures

Primary Outcome Measures

Number of Participants with Dose-limiting Toxicities (DLTs) [Baseline up to Cycle 1 (Cycle length is equal to [=] 28 days)]
DLT 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).
Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) [Up to 30 days after the last dose of study drug or before initiating post anti-cancer treatment (approximately 5 years)]

Secondary Outcome Measures

Cmax: Maximum Observed Plasma Concentration for E7386 [Dose Escalation Part: Cycle 1 Day 1: 0-12 hours; Cycle 1 Day 8: 0-12 hours; Cycle 2-6, Day 1: Pre-dose; Dose Expansion: Cycle 1 Day 1: 0-2 hours; Cycle 1 Day 8: 0-2 hours; Cycle 2 Day 1: Pre-dose (Cycle length=28 days)]
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for E7386 [Dose Escalation Part: Cycle 1 Day 1: 0-12 hours; Cycle 1 Day 8: 0-12 hours;; Cycle 2-6, Day 1: Pre-dose; Dose Expansion: Cycle 1 Day 1: 0-2 hours; Cycle 1 Day 8: 0-2 hours; Cycle 2 Day 1: Pre-dose (Cycle length=28 days)]
AUC: Area Under the Plasma Concentration Versus Time Curve for E7386 [Dose Escalation Part: Cycle 1 Day 1: 0-12 hours; Cycle 1 Day 8: 0-12 hours;; Cycle 2-6, Day 1: Pre-dose; Dose Expansion: Cycle 1 Day 1: 0-2 hours; Cycle 1 Day 8: 0-2 hours; Cycle 2 Day 1: Pre-dose (Cycle length=28 days)]
CL/F: Apparent Total Body Clearance for E7386 [Dose Escalation Part: Cycle 1 Day 1: 0-12 hours; Cycle 1 Day 8: 0-12 hours;; Cycle 2-6, Day 1: Pre-dose; Dose Expansion: Cycle 1 Day 1: 0-2 hours; Cycle 1 Day 8: 0-2 hours; Cycle 2 Day 1: Pre-dose (Cycle length=28 days)]
Vz/F: Apparent Volume of Distribution for E7386 [Dose Escalation Part: Cycle 1 Day 1: 0-12 hours; Cycle 1 Day 8: 0-12 hours;; Cycle 2-6, Day 1: Pre-dose; Dose Expansion: Cycle 1 Day 1: 0-2 hours; Cycle 1 Day 8: 0-2 hours; Cycle 2 Day 1: Pre-dose (Cycle length=28 days)]
Percentage of Participants with Best Overall Response (BOR) [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 5 years)]
BOR is defined as complete response (CR), partial response (PR), stable disease (SD), PD, and not evaluable (NE), where SD has to be achieved at greater than or equal to (>=) 7 weeks after the first dose. The BOR will be assessed by investigator based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
Objective Response Rate (ORR) [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 5 years)]
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 RECIST version 1.1.
Disease Control Rate (DCR) [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 5 years)]
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 RECIST version 1.1.
Clinical Benefit Rate (CBR) [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 5 years)]
The CBR is defined as the percentage of participants with a BOR of CR, PR, or durable SD (duration of SD >=23 weeks). The CBR will be assessed by investigator based on RECIST version 1.1.
Progression-free Survival (PFS) [From first dose of study drug until PD, or death from any cause, whichever occurs first (up to approximately 5 years)]
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.
Duration of Response (DOR) [From the date of first documented CR or PR until first documentation of PD or death (up to approximately 5 years)]
DOR is defined as the time from the first date of documented CR or PR to the date of PD or death, whichever occurs first. It will be calculated for participants whose BOR is CR or PR. DOR will be assessed according to RECIST version 1.1.
Overall Survival (OS) [From first dose of study drug until date of death (up to approximately 5 years)]
OS is defined as the time from the date of first dose to the date of death.

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Participants with a histological and/or cytological diagnosis of solid tumor must have any of the following tumor types:
Dose Escalation Part: Participants with advanced, unresectable, or recurrent solid tumor including CRC for which no alternative standard therapy or no effective therapy exists
Expansion Part: Participants with advanced, unresectable, or recurrent CRC in third- or later-line, Or subjects with other gastrointestinal tumors such as small bowel carcinoma and gastrointestinal neuroendocrine tumors after at least 1 prior systemic chemotherapy regimen upon discussion and agreement with the sponsor
Dose Escalation Part: Participants with CRC must consent to biopsy and submit the archival tumor tissue if it is stored.

Expansion part: Participants with accessible tumors must consent to tumor biopsy. Participants with inaccessible tumors may be enrolled without a biopsy upon consultation and agreement by the sponsor. Participants must consent to submit the archival tumor tissue if it is stored.

Life expectancy of >=12 weeks.
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1.
All AEs due to previous anti-cancer therapy have either returned to Grade 0-1 except for alopecia and 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 more
Any 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
Adequate renal, bone marrow, liver function, and serum mineral level.
At least one measurable lesion based on RECIST 1.1.
Participants must agree to take Vitamin D continuous supplementation as per local institutional guideline/ investigators clinical discretion when 25-hydroxyvitamin D levels less than ng/mL (nanogram per milliliter).
Dose escalation part: Participants must consent to skin biopsies from skin tissue that is tumor-free during the study. Expansion part: Initial At least 5 participants in each dose level must consent to skin biopsies from skin tissue that is tumor-free during the study. Participants may be enrolled without skin biopsies upon consultation and agreement by the sponsor.

Exclusion Criteria:

Known to be human immunodeficiency virus (HIV) positive.
Active infection requiring systemic treatment.
Diagnosed with meningeal carcinomatosis.
Participants with brain or subdural metastases are not eligible, unless they have completed local therapy and have discontinued the use of corticosteroids for this indication for at least 4 weeks before starting treatment in this study. Any signs (example: radiologic) or symptoms of brain metastases must be stable for at least 4 weeks before starting study treatment.
Pulmonary lymphangitic involvement that results in pulmonary dysfunction requiring active treatment, including the use of oxygen.
Inability to take oral medication, or malabsorption syndrome or any other uncontrolled gastrointestinal condition (example: nausea, diarrhea, or vomiting) that might impair the bioavailability of E7386.
Any of bone disease/conditions as follows;
Osteoporosis with T-score less than (<) -2.5 by Dual energy X-ray absorptiometry (DXA) scan
Fasting Beta-isomerised carboxy terminal telopeptide of type I collagen (β-CTX) (serum) Dose escalation part: greater than (>) 1000 picograms per milliliter (pg/mL) Expansion part: Participant who do not agree to start the treatment of anti-resorptive agent (example: bisphosphonate) when fasting β-CTX (serum) >1000 pg/mL and Grade 1 osteoporosis
Osteomalacia
Symptomatic hypercalcemia requiring bisphosphonate therapy
History of any fracture within 6 months prior to starting study drug
Any ongoing condition requiring orthopedic intervention
For participants with bone metastases, lack of treatment with a bisphosphonate or denosumab (participants with previous solitary bone lesions controlled with radiotherapy are eligible)
History of active malignancy (except for original disease, or definitively treated melanoma in-situ, basal or squamous cell carcinoma of the skin, carcinoma in-situ of the bladder or cervix, or early stage gastric/colorectal cancer) within the past 24 months prior to the first dose of study drug.
Prior treatment with E7386.

Contacts and Locations

Locations

	Site	City	State	Country
1	Eisai Trial Site #2	Kashiwa	Chiba	Japan
2	Eisai Trial Site #3	Nagaizumi-cho	Shizuoka	Japan
3	Eisai Trial Site #1	Chuo Ku	Tokyo	Japan
4	Eisai Trial Site #4	Fukuoka		Japan