Patient case: 64-year-old male with gastric cancer; genetic feature: ERBB2 amplification

Clinical trial: A Study of E7130 in Participants With Solid Tumors

Summary: The primary objective of this study is to evaluate the tolerability and safety profile of E7130 in participants with advanced solid tumors.


Eligibility: Inclusion Criteria:
  -  Participants who have provided voluntary written consent for participation in this clinical study
  -  Participants to whom the rules for complying with this clinical study have been adequately explained, and who intend to and can comply with those rules
  -  Participants age ≥ 20 years at the time of informed consent
  -  Participants with a histological and/or cytological diagnosis of solid tumor who failed standard therapies, or for which no appropriate treatment is available
  -  Participants with adequate function of major organs
  1. Hemoglobin ≥ 9.0 grams per deciliter
  2. Neutrophil count ≥ 1.5 x 10^3/microliter (µL)
  3. Platelet count ≥ 10 x 10^4/µL
  4. Total bilirubin ≤ 1.5 x upper limit of normal (ULN) in the facility
  5. Alanine aminotransferase and aspartate aminotransferase ≤ 3.0 x ULN in the facility
  6. Serum creatinine ≤ 1.5 x ULN in the facility
  -  Participants with Performance Status score of 0 to 1 established by the Eastern Cooperative Oncology Group
  -  Participants who are expected to survive for 3 months or longer after starting administration of the investigational drug
  -  Washout period required from the end of prior treatment to the first administration of study drug will be as follows:
  a. Anticancer therapy i. Antibody and other study drugs: > 4 weeks (however, in the case where the half-life of other study drugs is known and 5 × half-lives of that study drug is less than or equal to 4 weeks, participants can be eligible after ≥ 5 × half-lives of that study drug has passed) ii. Prior chemotherapy (except small-molecule targeted therapy), surgical therapy, radiation therapy: > 3 weeks iii. Endocrine therapy, immunotherapy (except antibody drug), small-molecule targeted therapy: > 2 weeks b. Supportive therapies i. Blood/platelet transfusion, hematopoietic stimulating agent including granulocyte colony-stimulating factor formulation: > 2 weeks
  -  Participants agree to submit blood samples prior and during study treatment for progressive disease markers.
  -  (Part 1 only in some of additional participants to explore candidate optimal biologic dose) Participants agree to be hospitalized between Cycle 1 Day 1 (C1D1) and C1D8 at least so that plasma, urine, and feces samples for pharmacokinetic analysis could be submitted.
  Inclusion Criteria (Part 2 only):
  -  Measurable disease meeting the following criteria:
  1. At least 1 lesion of ≥1.0 centimeters (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 Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 using computerized tomography/magnetic resonance imaging
  2. Lesions that have had external beam radiotherapy or locoregional therapies such as radiofrequency ablation must show evidence of progressive disease based on RECIST 1.1 to be deemed a target lesion
  Inclusion Criteria (Part 2: Her2-negative breast cancer cohort only):
  -  Histologically or cytologically confirmed adenocarcinoma of Her2-negative breast cancer
  -  Female participants who had received at least an anthracycline and/or taxane treatment for the neoadjuvant/adjuvant or chemotherapy for refractory or relapse breast cancer and progressed radiographically
  Inclusion Criteria (Part 2: Other solid tumors cohort only):
  -  Any refractory or relapse solid tumor types as follows:
  1. Histologically or cytologically confirmed diagnosis of squamous cell carcinoma of head and neck (oropharynx, hypopharynx, larynx)
  2. Histologically or cytologically confirmed diagnosis of other tumor (e.g., gastric or gastro-esophageal adenocarcinoma, and colon/rectum adenocarcinoma)
  Exclusion Criteria:
  -  Medical history of clinically significant cardiovascular impairment:
  1. Congestive heart failure greater or equal to than New York Heart Association Class II
  2. Unstable angina pectoris, myocardial infarction or stroke within 6 months before of the first dose of study drug
  3. Prolongation of corrected QT interval to > 480 milliseconds (ms) (Fridericia method)
  4. Arrhythmias requiring treatment
  -  Concomitant systemic infection requiring medical treatment (including bacterial infection and fungal infection)
  -  Participants who test positive for human immunodeficiency virus (HIV antibody)
  -  Active viral hepatitis (B or C) (*) as demonstrated by positive serology or requiring treatment (*)hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs)/hepatitis B core antibody (HBcAb) and anti-hepatitis C virus (HCV) antibody test. Participants who are anti-HBs/HBcAb (+) with less than 20 international units per milliliter (IU/ml) hepatitis B virus-deoxyribonucleic acid (HBV-DNA) are eligible.
  -  Effusion requiring drainage (Note: participants whose symptom has been treated and stable for 2 weeks prior to the first administration of the study drug, are eligible)
  -  Participants whose toxicity of previous treatment has not recovered to Grade 1 or lower (except for alopecia)
  -  Other active malignancy (except for definitively treated melanoma in-situ, basal or squamous cell carcinoma of the skin, or carcinoma in-situ of the cervix) within the past 24 months prior to the first administration of the study drug
  -  Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive beta-human chorionic gonadotropin [ß-hCG] or human chorionic gonadotropin [hCG]). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 3 days before the first dose of study drug (breastfeeding participants are not eligible even if they discontinue breastfeeding).
  -  Women of childbearing potential or men of impregnate potential who don't agree that both the participant and his/her partner will use a medically effective method for contraception (as below) during the study and after study drug discontinuation (male; 90 days, female; 60 days) Note: Condom*, contraceptive sponge**, foam**, jelly**, diaphragm*, intrauterine device *, or use of oral contraception* from at least 4 weeks before starting the study treatment (*Approved drugs or certified medical devices in Japan; **Non-approved drugs or certified medical devices in Japan)
  -  Known intolerance to the study drug or any of the excipients
  -  Any medical or other condition that in the opinion of the investigator(s) would preclude the participant's participation in the study
  -  Scheduled for surgery during the study
  -  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 (e.g., radiologic) or symptoms of brain metastases must be stable for at least 4 weeks before starting study treatment.
  Exclusion Criteria (Part 2 only):
  - Previous treatment with halicondrin B or -like compound.

Relevance to patient case: not relevant