An Open-label Phase 1 Study of E7386 in Subjects With Advanced Solid Tumor Including Colorectal Cancer
Overview
- Phase
- Phase 1
- Intervention
- E7386
- Conditions
- Solid Neoplasms
- Sponsor
- Eisai Co., Ltd.
- Enrollment
- 70
- Locations
- 8
- Primary Endpoint
- Number of Participants with Dose-limiting Toxicities (DLTs)
- Status
- Active, not recruiting
- Last Updated
- 8 months ago
Overview
Brief Summary
This study will be conducted to assess the safety and tolerability of E7386 in participants with solid tumor including CRC.
Detailed Description
The study will be conducted in 3 parts: dose escalation part, expansion part 1 and expansion part 2. The study will consist of Primary Assessment Phase and Continuation Phase. Primary Assessment Phase will include Pre-treatment Phase, Treatment Phase and Extension Phase (in expansion parts only). After Treatment Phase, participants will be followed in follow-up period of Extension Phase (in expansion parts only). All participants who are still on study drug at the time of data cutoff date for the planned primary analysis will enter the Continuation phase and continue to receive E7386.
Investigators
Eligibility Criteria
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 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
Exclusion Criteria
- •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;
Arms & Interventions
Dose Escalation Part: E7386
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.
Intervention: E7386
Expansion Part 1
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.
Intervention: E7386
Expansion Part 2
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.
Intervention: E7386
Outcomes
Primary Outcomes
Number of Participants with Dose-limiting Toxicities (DLTs)
Time Frame: 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)
Time Frame: Up to 30 days after the last dose of study drug or before initiating post anti-cancer treatment (approximately 6 years)
Secondary Outcomes
- 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))
- 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))
- 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))
- 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 6 years))
- 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 6 years))
- 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 6 years))
- Progression-free Survival (PFS)(From first dose of study drug until PD, or death from any cause, whichever occurs first (up to approximately 6 years))
- Duration of Response (DOR)(From the date of first documented CR or PR until first documentation of PD or death (up to approximately 6 years))
- Overall Survival (OS)(From first dose of study drug until date of death (up to approximately 6 years))