臨床研究等提出・公開システム

Phase I/II investigator-initiated clinical trial of MIKE-1 with Gemcitabine and Nab-paclitaxel combination therapy for unresectable pancreatic cancer

MIKE-1

Kawashima Hiroki

Nagoya university hospital

65 Tsurumai-cho, Showa-ku, Nagoya 466-8560

h-kawa@med.nagoya-u.ac.jp

Mizutani Yasuyuki

Nagoya university hospital

65 Tsurumai-cho, Showa-ku, Nagoya 466-8560

+81-52-741-2111

y-mizu@med.nagoya-u.ac.jp

Recruiting

Aug. 23, 2021

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

1. Patients with unresectable pancreatic cancer who are histologically or cytologically diagnosed as adenocarcinoma based on the 7th edition of the Pancreatic Cancer Treatment Protocol and meet the following criteria.
Patients who have not received any anticancer therapy (radiation therapy, chemotherapy, immunotherapy, surgery, or investigational therapy) for this disease.
2. Patients who are between 20 and 79 years of age at the time of consent.
3. Patients with at least one measurable lesion based on RECIST ver 1.1 in the primary pancreatic lesion confirmed by contrast-enhanced CT at the screening.
4. patients who are expected to survive for at least 12 weeks after the start of treatment.
5. patients who can understand the contents of this study and can give written consent.
6. patients with ECOG PS (Eastern Cooperative Oncology Group Performance Status) of 0 or 1
7. Patients who meet the criteria in blood tests within 7 days before enrollment and whose organ functions are preserved.
8. outpatients who can go to the hospital.
9. Patients who can swallow or continue to take oral medications.
10. for women of childbearing potential, patients who can use contraception for at least 30 days before the start of study treatment, during the study period, and for at least 2 years after the end of treatment.
11. patients who can undergo biopsy from pancreatic cancer within 28 days before the start of the study treatment and 8 weeks after the start of the study treatment (Day 57: acceptable range: 7 days)

1. Patients with any of the following complications
Patients with poorly controlled heart disease (congestive heart failure, myocardial infarction, or unstable angina within 1 year before enrollment, arrhythmia requiring treatment, etc.)
Poorly controlled diabetes or hypertension
Active autoimmune disease requiring systemic administration of steroids or immunosuppression therapy
Interstitial pneumonia or pulmonary fibrosis (patients with current grade 2 or higher)
2. patients who have received other clinical trial drugs or products (excluding existing chemotherapeutic agents and placebo drugs) within 4 weeks before enrolment.
3. Patients with confirmed brain metastasis (confirmed by head CT or MRI if the patient has symptoms of brain metastasis)
4. Patients with ascites or pleural effusion requiring drainage.
5. patients who fall under any of the following
HBs antigen positive
HCV antibody positive and HCV-RNA positive
HIV antibody positive
6. Patients with Grade 2 or higher peripheral sensory or motor neuropathy
7. Patients with multiple cancers (multiple cancers are defined as simultaneous multiple cancers and metachronous multiple cancers with disease-free survival of 5 years or less. lesions equivalent to carcinoma in situ or intramucosal carcinoma that are considered curable by local treatment are not included in multiple cancers)
8. Patients who have undergone surgery (excluding diagnostic biopsy and review laparoscopy) within 4 weeks before enrollment.
9. Patients with bleeding disorders or coagulation disorders that preclude the safe biopsy under EUS (e.g., significant intratumoral bleeding, coagulation disorders, history of bleeding disorders, or complications).
10. patients with a history of allergy to the trial drug, combination chemotherapy, its additives, or vitamin A products.
11. Patients requiring anticoagulant medication
12. Patients with cerebral infarction, pulmonary infarction, other arterial or venous thrombosis or its sequelae with clinical symptoms
13. Patients with gastrointestinal disorders that may affect the absorption of the investigational drug.
14. female patients who are pregnant or breastfeeding (unless breastfeeding is discontinued and not resumed)
15. male patients whose sex partner is a woman who wishes to become pregnant
16. patients with vitamin A overload
17. patients receiving vitamin A preparations or regularly using vitamin A-containing supplements (patients can be enrolled if the administration is discontinued at the time of obtaining consent)
18. other patients deemed inappropriate by the investigator or sub-investigator

Both

Patients with untreated, non-resectable pancreatic cancer

Phase I trial: The dose-limiting toxicity (DLT) assessment period will be set at 4 weeks. After the DLT evaluation period, if no disease progression is observed based on RECIST v1.1, or no unacceptable toxicities are observed in the patient, the investigational drug will be administered orally twice a day after breakfast and dinner for up to 6 courses for each dosage group. However, for the modified dosage level 2 of the Phase I trial, the investigational drug will be administered orally twice a day after breakfast and dinner, starting from the first day (Day 1) of each course, and drug administration will be paused starting from the Day 15 GEM/nab-PTX administration. Furthermore, dose reduction or increase of the investigational drug will not be performed on the same subject.
6 mg dosage group (Level 1): 3 MIKE-1 1 mg soft capsules per dose.
8 mg dosage group (Level 2 & Modified dosage level 2): 4 MIKE-1 1 mg soft capsules per dose.
4 mg dosage group (Level 0):* 2 MIKE-1 1 mg soft capsules per dose.
To be considered if in Level 1, DLT is observed in more than 2 cases and is present in more than 33% of the cases.

Phase II trial: The investigational drug at the clinically recommended dose determined in the Phase I trial will be administered orally twice a day after breakfast and dinner, starting from the first day (Day 1) of each course, and drug administration will be paused starting from the Day 15 GEM/nab-PTX administration. This will continue for up to 6 courses. Furthermore, dose reduction or increase of the investigational drug will not be performed on the same subject.

Unresectable pancreatic cancer

Tamibarotene, AM-80

D021441

D017426, D017427

Phase I study; DLT (dose-limiting toxicity)
Phase II study; response rate (based on RECIST ver1.1)

Adverse events
Overall survival (OS)
Progression-free survival (PFS)
MIKE-1 levels in blood (Phase I only)
Response rate (Phase I, based on RECIST ver1.1)
Vital signs and clinical laboratory values

+81-52-744-1958

April. 19, 2021

+81-3-5800-8743

April. 19, 2021

No

none