Necitumumab and Gemcitabine combination therapy for advanced Biliary tract cancer with EGFR Amplification phase2 Trial

JRCT ID: jRCTs031230259

Registered date:27/07/2023

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: biliary tract cancer
• Date of first enrollment: 19/04/2024
• Target sample size: 18
• Study type: Interventional
• Intervention(s): 1 Cycle: 21 days (Day 1, Day 8: Nesitumumumab 80 0 mg, gemcitabine 1000 mg/m2 (gemcitabine) for intravenous infusion; Day 15: rest). Ten cycles of tr eatment are performed.

Outcome(s)

• Primary Outcome: objective response rate (for periods of up to 6 cycle s of administration)

Secondary Outcome

Tumor control rate
Progression-free survival
Overall Survival
Adverse event rate

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

Patients who fulfill all of the following conditions are eligible for this study.
1) Patients with unresectable or recurrent biliary tract cancer diagnosed as biliary tract cancer by pathological diagnosis (cytological or histological diagnosis).
2) Patients must be at least 18 years of age.
3) Patients have a cancer genome profiling test that indicates EGFR amplification.
4) Patient is refractory to first-line therapy including gemcitabine.
5) The patient is refractory or intolerant to treatment with a companion diagnostic agent, pembrolizumab, if the cancer genome profiling test results in TMB-H or MSI-H.
6) The patient has measurable disease according to RECIST guideline Version 1.1.
7) ECOG Performance Status is 0 or 1.
8) No history of blood transfusion or G-CSF administration within 7 days prior to the examination, and no major abnormal findings in the latest laboratory values within 7 days prior to enrollment (laboratory values obtained on the same day of blood transfusion or G-CSF administration are acceptable).
1. Neutrophil count 1500 per mm3 or higher
2. Hemoglobin 8.0 g/dL or more
3. Platelet count 100,000 per mm3 or higher
4. Total bilirubin less than or equal to 1.5 mg /dL
5. AST (GOT) less than or equal to 100 IU/L ( less than or equal to 200 IU /L in case of liver metastasis)
6. ALT (GPT) less than or equal to 100 IU/L ( less than or equal to 200 IU /L for liver metastasis)
7. Serum creatinine less than 1.5 mg /dL.
If serum creatinine exceed 1.5 mg/dL, the patient is eligible if the creatinine clearance (CCr)*1 exceeds 40 mL/min.
*: Measured CCr by 24-hour urine collection or calculated using the Cockcroft-Gault estimation formula.
Men CCr = (140 - age) x weight (kg) / 72 / serum creatinine level (mg /dL)
Women CCr = 0.85 x (140 - age) x body weight (kg) / 72 / serum creatinine level (mg /dL)
9) Written consent is obtained from the patient after sufficient explanation of the study contents.
10) Treatment is possible on an outpatient basis.

Exclude criteria

1) Cancer genome profiling tests have been performed, and pathogenic gene alterations in KRAS, NRAS, and BRAF, which are located down stream of EGFR, as well as in EGFR itself, have been pointed out. Pathogenic fusion genes of FGFR2, NTRK1, NTRK2, NTRK3, RET for which companion diagnostic agents exist have been pointed out. When there is a difference in judgment as to whether these gene alterations are pathogenic or not, or when the detected frequency is low, a comprehensive judgment is made based on the results of the expert panel that examined the treatment options associated with the cancer genome profiling test.
2) Patient is intolerant of primary therapy including gemcitabine.
3) Patients have been treated with anti-EGFR antibody drugs.
4) Patients with metastasis to the central nervous system (brain, spinal cord, meninges) with symptoms.
5) Patients with active multiple cancers.
6) Patient has a local infection or active systemic infection requiring treatment.
7) Have a clinically problematic psychiatric disorder that would preclude enrollment in the study.
8) Patients with interstitial pneumonia/pulmonary fibrosis, unstable angina (angina with onset or worsening within the last 3 weeks), myocardial infarction within the last 6 months, untreated and uncontrolled thrombosis (deep vein thrombosis, pulmonary artery thrombosis, etc.), or other complications deemed serious by the treating physician.
9) HBs antigen positive.
10) HBs antigen negative but HBc antibody positive and/or HBs antibody positive, and HBV-DNA real-time PCR quantification method is 20 IU/mL (1.3 Log IU/mL) or more.
11) Patients with diabetes mellitus uncontrolled by medication (fasting blood glucose level of 130 mg/dL or higher).
12) Patients who are pregnant, may become pregnant, or wish to become pregnant during the treatment period.
13) Patients who have participated in a clinical trial or clinical study of a drug or medical device at the same time as this study or within 30 days prior to enrollment in this study.
14) Patients who have received any of the following treatments within the prescribed time period prior to enrollment in the study.
1. The last administration of a cytotoxic anticancer drug within 2 weeks prior to enrollment.
2. Received prior therapy (chemotherapy, molecular targeted therapy, antibody therapy, hormone therapy, immunotherapy, or radiation therapy) within 2 weeks prior to enrollment.
3. Underwent major surgery (minor surgery such as lymph node biopsy, needle biopsy, port placement, etc. are not applicable) within 2 weeks prior to enrollment.
15) Patients who have undergone major surgery (minor surgery such as lymph node biopsy, needle biopsy, port placement, etc. is not applicable) within 2 weeks prior to enrollment.

Related Information

• Primary Sponsor: Sugimori Makoto
• Secondary Sponsor: Maeda Shin
• Source(s) of Monetary Support: Public University Corporation Yokohama City University