Phase II Study of AM80 and Pembrolizumab in Pancreatic Cancer Patients with Late-Line Therapy

JRCT ID: jRCTs041230168

Registered date:01/04/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: pancreatic cancer
• Date of first enrollment: 01/04/2024
• Target sample size: 12
• Study type: Interventional

Intervention(s)

Administer AM80 at a dose of 6 mg/m2, divided into two daily doses to be taken post-breakfast and post-dinner, commencing one week prior to the initiation of pembrolizumab and continuing up to the day before the start of pembrolizumab administration, spanning a duration of 7 days through oral administration. Following the completion of AM80 administration, administer pembrolizumab at a dose of 200 mg once, via intravenous infusion, at an interval of three weeks.
Each interval of three weeks (21 days) constitutes one treatment course. The treatment is to be continued for a maximum of eight courses, unless there is progression of the disease or the emergence of intolerable adverse events. The administration of AM80 and pembrolizumab may be discontinued, interrupted, or resumed depending on the participant's condition.

Outcome(s)

• Primary Outcome: Response rate (RR)

Secondary Outcome

Overall survival (OS)
Progression-free survival (PFS)
Duration of Response(DOR)
Disease control rate (DCR)

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: <= 79age old
• Gender: Both

Include criteria

Patients will be included in the study if they meet all of the following criteria:
1 Patients histologically or cytologically diagnosed with pancreatic cancer based on the 7th edition of the pancreatic cancer treatment guidelines.
2 Patients with unresectable pancreatic cancer, including recurrence, who are resistant or intolerant to two types of standard treatments (secondary treatment resistance).
3 Patients who, at the time of screening, have lesions measurable according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria as assessed by contrast-enhanced Computed Tomography (CT).
4 Patients with one or more lesions that are biopsiable and deemed suitable for biopsy by the study principal investigator or co-investigator.
5 Patients with a performance status (PS) of 0-1 according to the Eastern Cooperative Oncology Group (ECOG) at the time of consent and are capable of taking oral medication.
6 Patients expected to survive more than 12 weeks from the start date of AM80 administration.
7 Patients whose major organ functions meet the following criteria at the time of screening (use the most recent results prior to registration in case of multiple results within the period):
a)Neutrophil count: >=1,500/microliter
b)Platelet count: >=100,000/microliter
c)Hemoglobin (Hb): >=9.0g/dL
d)Total bilirubin: <=1.5 times the upper limit of the facility standard (or <=3 times for obstructive jaundice or liver metastases due to the primary disease)
e)Aspartate Amino Transferase (AST) and Alanine Amino Transferase (ALT): <=3 times the upper limit of the facility standard (or <=5 times for obstructive jaundice or liver metastases)
f)Creatinine (Cr) <=1.5 times the upper limit of the facility standard, or Creatinine Clearance (CrCl) >=30 mL/min if Cr exceeds 1.5 times the facility standard
g)International Normalized Ratio (INR), Prothrombin Time (PT), activated Partial Thromboplastin Time (aPTT), or Partial Thromboplastin Time (PTT): <=1.5 times the upper limit of the facility standard
8 Male patients who can use contraception for 6 months after the end of AM80 administration, or female patients with the potential to become pregnant who can use contraception for 2 years after the end of AM80 administration, starting 30 days prior to the start of AM80 administration.
9 Patients aged 18 to 79 years at the time of consent (gender is not specified).
10 Patients who have received adequate explanation about this clinical study and have given their voluntary written consent.

Exclude criteria

1 Patients identified as having high-frequency microsatellite instability (MSI-High) or a high tumor mutational burden (TMB-High).
2 Patients who, at the time of enrollment, are within 21 days of the last administration of anticancer agents (chemotherapy, immunotherapy, biotherapy, etc.).
3 Patients who participated in other clinical trials within 21 days prior to enrollment (if the trial is within the approved efficacy and dosage, it's permissible if it does not affect the evaluation) and are within 21 days of the last administration of drugs used in the clinical study.
4 Patients whose adverse events from previous treatments are not stable.
5 Patients with metastases to the central nervous system.
6 Patients with a history of secondary cancer with a disease-free interval of less than one year (excluding digestive cancers completely removed by endoscopic mucosal resection, fully resected cervical intraepithelial neoplasia, localized or assumed cured prostate cancer, fully resected skin basal/squamous cell carcinoma, and other early-stage solid cancers that are considered cured after radical treatment).
7 Patients who have previously been administered vitamin A preparations, are currently being administered vitamin A preparations, or habitually use supplements containing vitamin A.
8 Patients who have undergone surgery involving general anesthesia (excluding diagnostic biopsies) within 4 weeks prior to enrollment.
9 Patients with bleeding tendencies or coagulation abnormalities (e.g., significant intratumoral hemorrhage, coagulopathy, history or concomitant bleeding disorders), requiring anticoagulant or antiplatelet medication.
10 Patients with active infections requiring systemic administration of antibiotics, antifungals, or antivirals.
11 Patients positive for Hepatitis B surface antigen, Hepatitis C Virus (HCV) antibodies and HCV-RNA, or Human Immunodeficiency Virus (HIV) antigen or antibodies.
12 Patients with apparent interstitial lung disease (interstitial pneumonia, lung fibrosis, etc.) on imaging, or with a history of such diseases.
13 Patients with concurrent autoimmune diseases, a history of chronic or recurrent autoimmune diseases, or requiring systemic corticosteroids or immunosuppressants.
14 Patients with a history of or active tuberculosis.
15 Patients with significant ascites or pleural effusion requiring drainage.
16 Patients with clinical symptoms or findings of intestinal obstruction requiring intravenous or central venous nutrition.
17 Patients with gastrointestinal diseases that may affect the absorption of AM80.
18 Patients with a history of severe hypersensitivity or anaphylactic reactions to ingredients in the study drugs, vitamin A, or antibody preparations.
19 Patients who have been vaccinated with live or attenuated vaccines within 30 days prior to enrollment.
20 Patients with serious comorbidities (liver disease (Child-Pugh C), renal disease (CrCl less than 30 mL/min), heart disease, lung disease, blood disorders, brain disorders, etc.).
21 Patients with hypervitaminosis A.
22 Patients with a history of organ transplantation (including hematopoietic stem cell transplantation).
23 Breastfeeding women (except those who agree to stop breastfeeding during the clinical study period and for 6 months after the last administration of AM80).
24 Pregnant women or women with a positive pregnancy test (women of childbearing potential who have had menstruation in the past 12 months must undergo a pregnancy test; however, women who have not had menstruation in the past 12 months but cannot rule out the possibility of pregnancy for reasons such as chemical menopause must also undergo a pregnancy test).
25 Patients deemed inappropriate for participation in this clinical study by the principal investigator or co-investigators.

Related Information

• Primary Sponsor: Kawashima Hiroki
• Source(s) of Monetary Support: AMED