| Eligibility |
Inclusion Criteria:
1. Patients who provided written informed consent to be subjects in this trial
2. Patients at least 20 years of age on the day of providing consent
3. Dose-escalation cohort: Patients with histologically or cytologically confirmed
advanced or metastatic solid tumors.
Expansion cohort: Patients with histologically or cytologically confirmed advanced or
metastatic solid tumors (gastric, colorectal, or hepatocellular cancer).
4. Patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of
0 or 1
5. Patients capable of taking oral medication
6. Patients with evaluable or measurable lesions as per RECIST version 1.1
7. Patients with adequate organ function at the time of enrollment as defined below:
- Neutrophil count =1500mm3
- Platelet count =10.0 × 104/mm3
- Hemoglobin (Hb) = 9 g/dL,
- aspartate transaminase (AST), alanine transaminase (ALT) =100 U/L (=100 U/L in
patients with Hepatocellular carcinoma, =250 U/L in patients with liver
metastasis)
- Total bilirubin =1.5-mg /dL
- Creatinine =1.5--mg /dL
- Lipase = 80 IU/L
- Urinary protein: It satisfies one of the following (if any of the inspection
criteria are satisfied, other examination may not be carried out) (i) urinary
protein (test paper method) is 2+ or less (ii) Urine Protein Creatinine(UPC)
ratio <3.5 (iii) 24-hour urine protein was measured, urinary protein ? 3500 mg
- Prothrombin time (PT)- International normalized ratio(INR): = 1.5 (? 3.0 in case
of anticoagulant administration)
8. For women who are likely to become pregnant (including those without menstruation due
to medical reasons such as chemical menopause) Note 1, we agreed to double
contraceptive Note 2 for at least 5 months from consent acquisition patient to the
final administration of the investigational product. Also, patients who agreed not to
breast feeding for at least 5 months from acquiring consent to the final
investigational drug administration.
For men, patients agreeing to double contraceptive for at least 7 months from the time of
starting investigational drug administration to the final investigational drug
administration.
Note 1): A woman who is likely to become pregnant is a woman who has experienced menarche
and is not undergoing sterilization surgery (such as hysterectomy, bilateral salpingo
ligation or bilateral oophorectomy), a woman without menopause Everything is included. The
definition after menopause shall be amenorrhea continuously for 12 months or more even
though there is no noteworthy reason. Women who are using oral contraceptives or mechanical
contraceptive methods (such as intrauterine contraceptive devices or barrier methods) are
considered to be pregnant.
Note 2): With regard to contraception, it is necessary to use two of the vasectomy or
condom of a male patient or male male, the uterine tube ligation of a female patient or the
other woman, a contraceptive pessary, an intrauterine contraceptive device or an oral
contraceptive I need to agree to heavy contraception.
Exclusion Criteria:
1. Patients who have undergone systemic chemotherapy, radiotherapy, surgery, hormone
therapy, or immunotherapy <2 weeks before enrollment. Immune checkpoint blockade as
pretreatment is permitted.
2. Patients with a history of taking regorafenib.
3. Patients with hypertension that is difficult to control (systolic blood pressure =160
mmHg and diastolic blood pressure =90 mmHg) despite treatment with several hypotensive
agents
4. Patients with acute coronary syndrome (including myocardial infarction and unstable
angina), and with a history of coronary angioplasty or stent placement performed
within 6 months before enrollment
5. Patients with a large amount of pleural effusion or ascites requiring drainage.
6. Patients with a =grade 3 active infection according to NCI-CTCAE version 4.03
7. Patients with symptomatic brain metastasis
8. Patients with partial or complete gastrointestinal obstruction
9. Patients with interstitial lung disease with symptoms or signs of activity
10. Patients who test positive for either anti-HIV-1 antibodies, anti-HIV-2 antibodies,
hepatitis B surface antigen (HBsAg), or anti-hepatitis C virus (HCV) antibodies*
*Patients who test positive for either anti-Hepatitis B surface(HBs) or anti-
Hepatitis B core(HBc) antibodies, and those who have hepatitis B virus (HBV)-DNA
measurements greater than the detection sensitivity will also be excluded.
(However, patients with hepatocellular carcinoma in the expansion cohort will not be
excluded even if they test positive for HBsAg and anti-HCV antibodies.)
11. Patients with concurrent autoimmune disease, or a history of chronic or recurrent
autoimmune disease
12. Patients who require systemic corticosteroids (excluding temporary usage for tests,
prophylactic administration for allergic reactions, or to alleviate swelling
associated with radiotherapy) or immunosuppressants, or who have received such a
therapy <14 days before enrollment in the present study
13. Patients with a history or findings of =grade III congestive heart failure according
to the New York Heart Association functional classification
14. Patients with a seizure disorder who require pharmacotherapy
15. Patients who had grade 3 or higher bleeding during 4 weeks before enrollment
16. Patients undergoing major surgery (thoracotomy or laparotomy, etc.), laparotomy
biopsy, trauma within 28 days before registration. The same day of the week before 4
weeks can be registered (However, in case of an artificial anastomosis without
intestinal resection, it shall be within 14 days before registration).
17. Patients with non-healing wound, non-healing ulcer, or non-healing bone fracture.
18. Patients with a history of hypersensitivity to any of the study drugs, similar drugs,
or excipients.
19. Women who are pregnant or breastfeeding, or with the potential for pregnancy.
|
