| Eligibility |
Inclusion Criteria:
1. Male or female subject =18 years of age at the time of signing the informed consent
form (ICF).
2. Subjects with histologically or cytologically confirmed colorectal adenocarcinoma who
have failed or are ineligible for oxaliplatin and irinotecan-based chemotherapy.
3. Subjects with advanced/metastatic solid tumors, with evaluable lesion as determined by
Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1.
Measurable lesion is optional.
4. Eastern Cooperative Oncology Group Performance Status (ECOG PS) =2.
5. Adequate organ and bone marrow function characterized by the following at screening:
1. Absolute neutrophil count(ANC) =1.0 × 109/L;b.
2. Platelets =75 × 109/L;c.
3. Hemoglobin =9.0 g/dL (with or without blood transfusions).
4. Adequate renal function defined by Serum creatinine = ULN x 1.5 or an estimated
creatinine clearance =30 mL/min according to the Cockcroft Gault formula or by
24-hour urine collection for creatinine clearance, or according to local
institutional standard method.
5. Serum total bilirubin =2.0 x upper limit normal (ULN), if a subject with biliary
obstruction is considered suitable if they meet the criteria after appropriate
bile drainage.
6. ALT and AST = 3 × ULN, or =5 × ULN in the presence of liver metastases.
6. Adequate cardiac function: QTc =480 msec; if QTc exceeds 480 msec, subjects can be
enrolled if the average QTc value is less than 480 msec by measuring 3 times
consecutively in total.
7. The subject is able to swallow and retain oral medication
8. Serum ß hCG test negative within 14 days before the first administration of the study
treatment (women of childbearing potential only)
9. Requirement for contraception must be observed by the subject.
- Eligible women (all women of reproductive potential who are either undergoing
clinical trial treatment or within 4 weeks after discontinuing clinical trial
treatment, and who are not using appropriate contraception) must use the
following contraceptive methods to be eligible for enrollment.
- Subjects must abstain from all forms of sexual intercourse and are encouraged to
practice consistent abstinence in their daily lives. Periodic abstinence methods
(e.g., calendar-based methods, cervical mucus observation, basal body temperature
methods, etc.) and withdrawal are not considered acceptable contraceptive
methods.
- Accepted infertility surgical procedures: Bilateral oophorectomy with or without
hysterectomy; Tubal ligation at least 6 weeks before enrollment in this clinical
trial. Bilateral oophorectomy is only allowed if the subject's potential for
pregnancy is confirmed through hormone level assessment.
- In the case of female participants in the clinical trial, their male partners who
have undergone vasectomy (screening performed at least 6 months prior) should be
their exclusive partners during the participation in this clinical trial
- During the clinical trial, male participants should use condoms during sexual
intercourse while they are receiving the investigational drug and for up to 1
month after discontinuing the treatment (after the last dose).
10. Life expectancy of at least 12 weeks. Capable and willing to give signed informed
consent which includes compliance with the requirements and restrictions listed in the
ICF and in the protocol.
11. Subject has signed the Informed Consent Form (ICF) prior to any screening procedures
being performed
Exclusion Criteria:
1. Patient has a known or suspicious hypersensitivity to fluoropyrimidines.
2. Any cytotoxic chemotherapy from a previous treatment regimen within 14 days. If the
subject received an investigational drug from another clinical trial, the subject can
be enrolled after 2 weeks of last administration and more than 5 x half-life of the
investigational drug. If monoclonal antibody therapy was given, the subject can be
enrolled after four weeks after the last dose.
3. Uncontrolled severe infection
4. Subjects with conditions requiring high doses of steroids (>10 mg/day of prednisone or
equivalent) or other immunosuppressive medications are excluded, all of the following
will not be excluded:
1. Brief (<7 days) use of systemic corticosteroids is allowed when use is considered
standard of care.
2. Subjects requiring intermittent use of bronchodilators, inhaled steroids, or
local steroid injections will not be excluded.
3. Replacement therapy (e.g., thyroxine, insulin, physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency) is not considered a
form of systemic treatment and is allowed.
5. Subjects who are pregnant or breastfeeding women.
6. History of autoimmune disease that has required systemic treatment in the past 2 years
(i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive
drugs). Subjects with vitiligo, psoriasis not requiring systemic treatment, type 1
diabetes mellitus, hypothyroidism stable with hormone replacement, Sjögren's syndrome,
or resolved childhood asthma/atopy will not be excluded.
7. Active central nervous system (CNS) lesions (i.e., those with radiologically unstable
or symptomatic brain lesions). For those who receive radiation or surgical treatment,
the subject can be enrolled if the subject is maintained without steroid therapy and
the evidence of CNS disease progression for more than 4 weeks. However, patients with
leptomeningeal metastases are excluded.
8. Subjects with a documented history of a cerebral vascular event (stroke or transient
ischemic attack), unstable angina, myocardial infarction, or cardiac symptoms
consistent with New York Heart Association (NYHA) Class IV within 6 months prior to
screening.
9. Subjects with a history of idiopathic pulmonary fibrosis, organizing pneumonia, drug
induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on
screening chest computerized tomography (CT) scan.
10. Subjects who have received a prior allogeneic stem cell or solid organ transplant.
11. Subjects who have received a live attenuated vaccine within 30 days prior to
screening. Examples of live vaccines include, but are not limited to, the following:
measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies,
Bacillus Calmette Guérin, and typhoid vaccine. Seasonal influenza vaccines for
injection are generally killed virus vaccines and are allowed; however, intranasal
influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.
12. History of other primary cancer. Exceptions are as follows:
- Adequately treated non-melanoma skin cancer (basal cell or squamous cell carcinoma),
curatively treated in situ cancer of the cervix or stage I bladder cancer, completely
resected thyroid cancer without distant metastasis in which all treatment has been
completed (Appropriate wound healing is required prior to clinical trial enrollment)
13. Subject has not recovered to = grade 1 (except alopecia) from related adverse effects
of any prior anticancer therapy.
14. Radiotherapy with a wide field (more than 30% of the bone marrow) of radiation within
4 weeks or radiotherapy with a limited field of radiation for palliation within 2
weeks of the first dose of study treatment.
15. Subject who has undergone major surgery = 4 weeks prior to starting study treatment or
who has not recovered from adverse effects of such procedure.
16. Subjects with impaired gastrointestinal (GI) function or GI disease that may
significantly alter the absorption of capecitabine.
17. Subjects who have known active hepatitis B (defined as positive hepatitis B surface
antigen [HBsAg] with detected hepatitis B virus [HBV] DNA) or known active hepatitis C
virus (defined as HCV RNA [qualitative] is detected) infection.
18. Subjects with genetic conditions such as galactose intolerance, Lapp lactase
deficiency, or glucose-galactose malabsorption.
19. As judged by the Investigator, all other symptoms and associated disease for which the
investigator determined that participation in this study is contraindicated (e.g.
Infection/inflammation; severe liver dysfunction; bilateral diffuse interstitial lung
disease; uncontrolled renal disease; unstable heart and lung disease; hemorrhagic
disease; intestinal obstruction; unable to swallow oral pills; social and
psychological problems, etc.)
20. Medical, psychiatric, cognitive, or other conditions that may interfere with the
ability of the subject to understand the subject information, provide the informed
consent, follow the protocol process, or complete the clinical trial
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