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

NCT03833700 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: E7386-J081-103
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 8

Brief Summary

This study will be conducted to assess the safety and tolerability of E7386 in participants with solid tumor including CRC.

Conditions

Solid Neoplasms; Colorectal Neoplasms; Gastrointestinal Tumors

Keywords

Solid Tumor; Colorectal Cancer; E7386; Small Bowel Carcinoma; Gastrointestinal Neuroendocrine Tumor; Adrenocortical carcinoma; Desmoid Tumor; Solid pseudopapillary neoplasm of pancreas; Hepatocellular carcinoma

Outcome Measures

Primary Outcomes (2)

• Number of Participants with Dose-limiting Toxicities (DLTs)

  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).

  Baseline up to Cycle 1 (Cycle length is equal to [=] 28 days)

• 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 6 years)

Secondary Outcomes (11)

• Cmax: Maximum Observed Plasma Concentration for E7386

  Dose escalation Part, Cycles 1 to 6: Up to Day 8; Dose Expansion Part 1 and 2, Cycles 1 and 2: Up to Day 8 (Cycle length=28 days)

• Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for E7386

  Dose escalation Part, Cycles 1 to 6: Up to Day 8; Dose Expansion Part 1 and 2, Cycles 1 and 2: Up to Day 8 (Cycle length=28 days)

• AUC: Area Under the Plasma Concentration Versus Time Curve for E7386

  Dose escalation Part, Cycles 1 to 6: Up to Day 8; Dose Expansion Part 1 and 2, Cycles 1 and 2: Up to Day 8 (Cycle length=28 days)

• CL/F: Apparent Total Body Clearance for E7386

  Dose escalation Part, Cycles 1 to 6: Up to Day 8; Dose Expansion Part 1 and 2, Cycles 1 and 2: Up to Day 8 (Cycle length=28 days)

• Vz/F: Apparent Volume of Distribution for E7386

  Dose escalation Part, Cycles 1 to 6: Up to Day 8; Dose Expansion Part 1 and 2, Cycles 1 and 2: Up to Day 8 (Cycle length=28 days)

Study Arms (3)

Dose Escalation Part: E7386

EXPERIMENTAL

Participants will receive E7386 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.

Drug: E7386

Expansion Part 1

EXPERIMENTAL

Participants will receive E7386 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.

Drug: E7386

Expansion Part 2

EXPERIMENTAL

Participants will receive E7386 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.

Drug: E7386

Interventions

E7386 DRUG

E7386 doses.

Dose Escalation Part: E7386; Expansion Part 1; Expansion Part 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 1: Participants with advanced, unresectable, or recurrent CRC in third- or later-line, Or participants 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
• Expansion Part 2: Participants with advanced, unresectable, or recurrent solid tumors expected to be highly dependent on wingless/integrated (Wnt)/β-catenin signaling pathway as specified below, who have no standard therapy. Disease progression must be confirmed within the past 12 months.
• Desmoid tumor
• Solid pseudopapillary neoplasm (SPN) of pancreas
• Small bowel carcinoma with mutation of catenin beta-1 (CTNNB1) or adenomatous polyposis coli (APC)
• Adrenocortical carcinoma (ACC) with mutation of CTNNB1, APC or zinc and ring finger 3 (ZNRF3)
• Solid tumors (except for CRC) with APC mutation in participants diagnosed as familial adenomatous polyposis (FAP)
• Hepatocellular carcinoma (HCC) with CTNNB1 gain-of-function mutation
• Other types of solid tumors (except for CRC) harboring one or more Wnt-related gene mutations (example, APC, AXIN1, CTNNB1, ring finger protein 43 \[RNF43\], et cetera) expected to be highly dependent on Wnt/β-catenin signaling pathway based on emerging data may be enrolled upon consultation and agreement with the sponsor.
• HCC participants must have:
• A diagnosis of HCC that is histologically or cytologically confirmed (excluding fibrolamellar, sarcomatoid or mixed cholangio-HCC tumors) or clinically confirmed according to American Association for the Study of Liver Disease criteria, including cirrhosis of any etiology and/or chronic hepatitis B or C infection.
• Barcelona Clinic Liver Cancer (BCLC) Stage C disease, or BCLC Stage B disease not amenable to locoregional therapy or refractory to locoregional therapy, and not amenable to a curative treatment approach
• Life expectancy of \>=12 weeks.

You may not qualify if:

• Known to be human immunodeficiency virus (HIV) positive.
• Active infection requiring systemic treatment.
• For participants with HCC in Expansion part 2: In case of Hepatitis B surface antigen (HBsA g) positive (+) participants:
• Antiviral therapy for Hepatitis B virus (HBV) is not ongoing
• HBV viral load is 2000 International units 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 Hepatitis C virus (HCV) infection (anti-HCV Ab \[+\] and detectable HCV Ribonucleic acid \[RNA\]) at study entry
• 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.
• Any of bone disease/conditions as follows;
• Osteoporosis with T-score less than (\<) -3 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 and no prior medical therapy for osteoporosis can only be included provided that treatment with a bisphosphonate (example, zoledronic acid) or denosumab has been started at least 14 days 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
• Any condition requiring orthopedic intervention

Sponsors & Collaborators

• Eisai Co., Ltd.: lead

Study Sites (8)

Eisai Trial Site#7

Nagoya, Aichi-ken, Japan

Location

Eisai Trial Site #2

Kashiwa, Chiba, Japan

Location

Eisai Trial Site #5

Sapporo, Hokkaido, Japan

Location

Eisai Trial Site#8

Sendai, Miyagi, Japan

Location

Eisai Trial Site #3

Nagaizumi-cho, Shizuoka, Japan

Location

Eisai Trial Site #1

Chuo Ku, Tokyo, Japan

Location

Eisai Trial Site #4

Fukuoka, Japan

Location

Eisai Trial Site#6

Osaka, Japan

Location

MeSH Terms

Conditions

Colorectal Neoplasms; Digestive System Neoplasms; Gastro-enteropancreatic neuroendocrine tumor; Adrenocortical Carcinoma; Desmoid Tumors; Carcinoma, Hepatocellular

Interventions

E-7386

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Adrenal Cortex Neoplasms; Adrenal Gland Neoplasms; Endocrine Gland Neoplasms; Adrenal Cortex Diseases; Adrenal Gland Diseases; Endocrine System Diseases; Fibroma; Neoplasms, Fibrous Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Liver Neoplasms; Liver Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 6, 2019
• First Posted: February 7, 2019
• Study Start: March 5, 2019
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): March 31, 2027
• Last Updated: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

JP (8)