Superficial Esophageal Cancer

The purpose of this study is to evaluate the efficacy and safety of esophageal epithelial regenerative treatment by the transplantation of the product, CLS2702C, to the esophageal wound site after extensive ESD for superficial esophageal cancer.

Human (autologous) oral mucosal cell sheet(CLS2702C)

Human (autologous) oral mucosal cell sheet

2-10

Length (cm) of resection site × % of circumference resected = necessary number of cell sheets

Primary endpoint
The primary endpoint of efficacy will be assessed based on the proportion of subjects without stenosis until
8 weeks after ESD. An endoscope with a diameter of 9.8 mm must pass without resistance. In addition,
endoscopic images on the oral proximal and anal sides of the operated lesion will be taken as records and
stored as source documents.
The endoscopic images, if it is judged that no stenosis is present, will cover the entire ESD site.
If stenosis is present, the stenosis-developing site will be pictured.

Secondary endpoints
Secondary endpoints of efficacy will be assessed as below.
1. Time to first appearance of post-ESD wound healing, regardless of stenosis (Wound healing is defined
as the re-epithelized state with no white coat, erosion, or ulcer in the process of healing.)
2. Time to post-ESD wound healing that is free of stenosis (Wound healing is defined as the reepithelized state with no white coat, erosion, or ulcer in the process of healing. In the case that the
stenosis is observed, the wound healing time should be calculated till stenosis is resolved for this
endpoint.)
3. Time to the first appearance of stenosis
4. Number of EBDs (investigated until wound healing that is free of stenosis is observed)
5. Incidence of adverse events and product deficiencies
6. EORTC QLQ-OG25
7. EORTC QLQ-C30 (version 3.0)
Time to first appearance of post-ESD wound healing (regardless of stenosis), time to post-ESD wound
healing that is free of stenosis, and time to the first appearance of stenosis will be assessed endoscopically.
The investigator/co-investigator will create a video recording featuring a portion of the ESD-treated lesion
from about 1 cm on the oral proximal side to about 1 cm on the anal distal side, with the entire esophagus
covered in the visual field, taken at the time of endoscopic examination except prior to transplantation,
store raw data at the institution, and provide a copy thereof on an electronic recording medium (CDR/DVD-R) for the sponsor.
If stenosis is present, further imaging will be unnecessary

Inclusion criteria
In order to be eligible to participate in this study, a subject must meet all of the following criteria:
1) Subject who plans to undergo ESD for the treatment of superficial esophageal cancer
2) Subject aged ≥20 years at the time of consent
3) Subject with no clinical metastasis (cN0M0) by cervical to abdominal CT or MRI
4) Subject with an endoscopically diagnosed depth of wall invasion remaining in the epithelium (EP) or
lamina propria mucosae (LPM)
5) Subject with ≥3/4 of predicted resection circumference and a length of 8 cm
6) If the subject has multiple lesions, the circumference of all minor lesions other than the one lesion with
the largest circumference (major lesion) must be <1/2, and the distance between the minor lesions and
the major lesion must be 5 cm or more on the major axis.
7) Subject with squamous cell carcinoma (including high-grade intraepithelial neoplasia) as confirmed
by biopsy
8) Subject whose lesion is confirmed to be localized in the thoracic esophagus (lesions in the cervical
esophagus or abdominal esophagus will be excluded). The location of the lesion will be determined
by endoscopy.
9) Subject who has not received pretreatment for esophageal cancer. Treatment by ESD or EMR for
superficial esophageal cancer for which the depth of wall invasion has been assessed to remain in the
epithelium (EP) or lamina propria mucosae (LPM) is not included in the definition of pretreatment.
However, subject who has a scar due to previous ESD or EMR in the target lesion site of this study
will be excluded.
10) Subject with an ECOG Performance Status (PS) of 0 or 1
11) Subject in whom a commonly used endoscope with a tip diameter of 9.8 mm can pass
12) Subject with a dysphagia score of 0
13) Subject whose laboratory values at screening meet all of the following criteria:
• White blood cell count: ≥4,000/µL
• Platelet count: ≥100,000/µL
• AST: ≤100 IU/L
• ALT: ≤100 IU/L
• Total bilirubin: ≤2.0 mg/dL
• Serum creatinine: ≤2.0 mg/dL
14) Subject who has received sufficient explanation about the clinical study and provided written voluntary
consent

Exclusion criteria
Any subject meeting any of the exclusion criteria will be excluded from study participation:
1) Subject with cardiac disease (myocardial infarction, unstable angina, and heart failure), renal disease
(nephrotic syndrome and kidney failure), or poorly controlled diabetes mellitus (HbA1c >10%)
2) Subject who has active head and neck cancer (within 6 months) or any active malignancy (within 1 year) other than esophageal cancer
3) Subject with active bacterial, fungal, or viral infection
4) Subject who is being treated with a corticosteroid (e.g. oral, injective, or inhalation)
5) Subject with positive HBs antigen, positive HCV antibody, positive HIV antigen, positive HIV
antibody, positive HTLV antibody, or positive Treponema pallidum antibody (tested at screening).
For subject with negative HBs antigen but with positive HBc antibody and/or HBs antibody, HBVDNA test will be performed (if the result of HBV-DNA test is negative, the subject will be allowed to
enter the study).
6) Subject with a mental disorder that is difficult to control
7) Pregnant female subject, lactating female subject, and potentially pregnant female subject
Lactating female subject may be enrolled in the clinical study if she discontinues lactation during the
period from transplantation to wound healing as defined in the secondary endpoint.
Female subject of childbearing potential must agree to use the following birth control methods or
completely abstain from sexual intercourse during the period from consent to participate in the clinical
study to the end of study participation:
Acceptable contraceptive forms include:
a. Established use of oral, injected or implanted hormonal methods of contraception
b. Placement of an intrauterine device (IUD) or intrauterine system (IUS)
c. Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps)
8) Subject who has participated in another clinical study within 4 weeks before Screening Visit, who is
participating in another clinical study, or who plans to participate in another clinical study during
participation in this clinical study
9) Subject from whom tissue cannot be collected due to a disease (e.g., stomatitis, erosion, mass, blister,
oral submucous fibrosis, or precancerous lesion) in the oral mucosa at the tissue collection site
10) Subject with a history of hypersensitivity to antibiotic preparations (ampicillin sodium, sulbactam
sodium, streptomycin sulfate, gentamicin sulfate, or amphotericin B) or who has taken drugs that may
affect the clinical study (within 4 weeks before Screening Visit)
11) Subject who has undergone radiotherapy in the cervical to upper abdominal region, or surgery for head
and neck cancer that may affect the assessment of ESD or stenotic symptoms
12) Subject whose swallowing function has been markedly reduced or completely lost due to a sequela of
cerebral infarction or other reasons
13) Subject with porcine or latex allergy
14) Subject who, in the opinion of the treating physician, is not eligible for the study due to reasons other
than those described above