MASCARPONE study

JRCT ID: jRCTs031220099

Registered date:30/05/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: rare fractions of hepato-pancreato-biliary cancer and neuroendocrine tumor
• Date of first enrollment: 18/08/2022
• Target sample size: 68
• Study type: Interventional

Intervention(s)

Patients continue to receive treatment unless the discontinuation criteria are met.
Cohort A:
nab-paclitaxel 125mg/m2 IV over 30 minutes, followed by
Gemcitabine 1000 mg/m2 IV over 30 minutes days 1, 8, and 15 of a 28-day cycle.
Cohort B:
Oxaliplatin 85 mg/m2 IV over 2 hours, followed by
l-leucovorin 200 mg/m2 IV over 2 hours,
Irinotecan 150 mg/m2 IV over 90 minutes (concurrent with l-leucovorin during the last 90 min of the leucovorin infusion)
5-FU 2400 mg/m2 continuous IV infusion over 46 hours every 2 weeks.
Cohort C:
Oxaliplatin 85 mg/m2 IV over 2 hours, followed by
l-leucovorin 200 mg/m2 IV over 2 hours,
Irinotecan 90 mg/m2 * IV over 90 minutes (concurrent with l-leucovorin during the last 90 min of the l-leucovorin infusion)
5-FU 2400 mg/m2 continuous IV infusion over 46 hours every 2 weeks.
*If safety is considered acceptable in cycle 1, escalate the dose of irinotecan to 120 mg/m2 in cycle 2.
Cohort D:
Atezolizumab 1200mg IV over 60 minutes, followed by Bevacizumab 15 mg/kg IV over 90 minutes every 3 weeks.

Outcome(s)

Primary Outcome

Cohort A: Objective response rate
Cohort B: Objective response rate
Cohort C: Objective response rate
Cohort D: Objective response rate

Secondary Outcome

Cohort A: Overall survival, progression-free survival, disease control rate, Duration of response, frequency of adverse events.
Cohort B: Overall survival, progression-free survival, disease control rate, Duration of response, frequency of adverse events.
Cohort C: Overall survival, progression-free survival, disease control rate, Duration of response, frequency of adverse events.
Cohort D: Overall survival, progression-free survival, disease control rate, Duration of response, frequency of adverse events, frequency of immune-related adverse event.

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

Cohort A
(1) Pathologically confirmed undifferentiated carcinoma of the pancreas;
(2) Unresectable disease diagnosed by contrast-enhanced CT (chest, abdomen, and pelvis) and/or MRI (abdomen and pelvis) imaging;
*If the patient received adjuvant chemotherapy and the diasese recurred within 6 months after the completion, the patient is excluded from this study.
(3) At least 20 years of age;
(4) Eastern Cooperative Oncology Group (ECOG) performance status of 0-1;
(5) Measurable disease by RECIST v1.1 criteria;
(6) No prior treatment for undifferentiated carcinoma of the pancreas;
(7) Adequate hematologic and organ function defined by the following laboratory test results, obtained within 7 days prior to study enrollment:
1) Absolute neutrophil count (ANC) >=1,500 /mm3,
2) Hemoglobin >= 8.0 g/dL,
3) Platelet count >= 10^4/mm3,
4) Serum total bilirubin <= 2.0 mg/dL,
5) Aspartate transaminase (AST) < 100 U/L without liver metastases (< 150 U/L is acceptable if liver metastases are present),
6) Alanine transaminase (ALT) < 100 U/L without liver metastases (< 150 U/L is acceptable if liver metastases are present),
7) Serum creatinine (Cr) <= 1.2 mg/dL
(8) Signed written informed consent form.

Cohort B
(1) Pathologically confirmed acinar cell carcinoma of the pancreas;
(2) Unresectable disease diagnosed by contrast-enhanced CT (chest, abdomen, and pelvis) and/or MRI (abdomen and pelvis) imaging;
*If the patient received adjuvant chemotherapy and the diasese recurred within 6 months after the completion, the patient is excluded from this study.
(3) 20-75 years of age;
(4) ECOG performance status of 0-1;
(5) Measurable disease by RECIST v1.1 criteria;
(6) No prior treatment for acinar cell carcinoma of the pancreas;
(7) Peripheral motor or sensory neuropathy <= grade 1;
(8) None of UGT1A1 polymorphisms (UGT1A1*6/*6, UGT1A1*28/*28, and UGT1A1*6/*28);
(9) Adequate hematologic and organ function defined by the following laboratory test results, obtained within 7 days prior to study enrollment:
1) Absolute neutrophil count (ANC) >=1,500 /mm3,
2) Hemoglobin >= 8.0 g/dL,
3) Platelet count >= 10^4/mm3,
4) Serum total bilirubin <= 1.5 mg/dL,
5) AST < 100 U/L without liver metastases (< 150 U/L is acceptable if liver metastases are present),
6) ALT < 100 U/L without liver metastases (< 150 U/L is acceptable if liver metastases are present),
7) Cr <= 1.2 mg/dL
(10) Signed written informed consent form.

Cohort C
(1) Pathologically confirmed adenocarcinoma;
(2) Metastatic or recurrent* pancreatic cancer diagnosed diagnosed by contrast-enhanced CT (chest, abdomen, and pelvis) and/or MRI (abdomen and pelvis) imaging;
*If the patient received adjuvant chemotherapy and the diasese recurred within 6 months after the completion, the patient is excluded from this study.
(3) Presence of UGT1A1 polymorphisms (UGT1A1*6/*6, UGT1A1*28/*28, and UGT1A1*6/*28);
(4) 20-75 years of age;
(5) ECOG performance status of 0-1;
(6) Measurable disease by RECIST v1.1 criteria;
(7) No prior treatment for pancreatic cancer;
(8) Peripheral motor or sensory neuropathy <= grade 1;
(9) Adequate hematologic and organ function defined by the following laboratory test results, obtained within 7 days prior to study enrollment:
1) Absolute neutrophil count (ANC) >=1,500 /mm3,
2) Hemoglobin >= 8.0 g/dL,
3) Platelet count >= 10 x 10^4/mm3,
4) Serum total bilirubin <= 2.0 mg/dL,
5) AST < 100 U/L without liver metastases (< 150 U/L is acceptable if liver metastases are present),
6) ALT < 100 U/L without liver metastases (< 150 U/L is acceptable if liver metastases are present),
7) Cr <= 1.2 mg/dL
(10) Signed written informed consent form.

Cohort D
(1) Histologically confirmed as combined hepatocellular-cholangiocellular carcinoma;
(2) Resection or locoregional therapy, such as local ablation or hepatic artery chemoembolization (TACE), is considered to be refractory or unsuitable due to vascular invasion, extrahepatic metastasis, or both diagnosed by abdominal contrast-enhanced CT or MRI examination within 28 days before registration.
(3) Child-Pugh classification A based on the most recent data before registration;
(4) At least 20 years of age;
(5) ECOG performance status of 0-1;
(6) Measurable disease by RECIST v1.1 criteria;
(7) No prior treatment for combined hepatocellular-cholangiocellular carcinoma;
(8) Adequate hematologic and organ function defined by the following laboratory test results, obtained within 7 days prior to study enrollment:
1) Absolute neutrophil count (ANC) >=1,500 /mm3,
2) Hemoglobin >= 8.5 g/dL,
3) Platelet count >= 6 x 10^4/mm3,
4) AST < 100 U/L without liver metastases (< 150 U/L is acceptable if liver metastases are present),
5) ALT < 100 U/L without liver metastases (< 150 U/L is acceptable if liver metastases are present),
6) Cr <= 1.2 mg/dL or Creatinine clearance >= 50 mL/min
7) Urine protein 2 plus or less; If urine protein is 3 plus or higher, the urine protein/urinary creatinine ratio is less than 2.0.
(9) Signed written informed consent form.

Exclude criteria

(1)History of malignancy (except for adequately treated carcinoma in situ, non-invasive cancer) within 2 years prior to study entry except if the patient has undergone potentially curative therapy with no evidence of that disease recurrence for 2 years;
(2)Evidence of uncontrolled, active infection, requiring anti-infectious treatment, except for viral hepatitis;
(3)Known central nervous system metastases (imaging required only if participants are symptomatic);
(4)Symptomatic ascites or pleural effusion;
(5)Significant lung disease, including interstitial lung disease, pulmonary fibrosis, or severe emphysema;
(6)Active watery diarrhea;
(7)Pregnant, lactating or females of childbearing age unless using highly effective contraception;
(8)Male with partner of child-bearing potential unless using highly effective contraception;
(9)Patients with significant psychiatric disorder;
(10)History of arterial thromboembolism (e.g., myocardial infarction, unstable angina, and cerebral infarction) within 6 months prior to the initiation of study treatment;
(11)Significant comorbidities, such as uncontrolled diabetes mellitus, uncontrolled hypertension, New York Heart Association (NYHA) Class III or greater cardiac disease, chronic kidney disease, or liver dysfunction;
(12)Requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalent) or other immunosuppressive medication;
(13)Esophageal or gastric varices with a risk of bleeding without preventive treatment;
(14) History of hypersensitivity to the study drugs used in each cohort;
(15)Patients whose entry in the study is considered by the investigator to be inappropriate.

Related Information

• Primary Sponsor: Ikeda Masafumi