Trastuzumab in HER2-positive Biliary Tract Cancer (BILHER)

The Pilot Study of Trastuzumab in Combination With Gemcitabine Plus Cisplatin for HER2-positive Biliary Tract Cancer

Trastuzumab is approved for the treatment of HER2-positive breast cancer and gastric cancer. The recent study showed that HER2 overexpression or amplification is noted about 5-15% of total biliary tract cancer patients. The aim of this study is to evaluate the efficacy and safety of trastuzumab in the combination of current standard gemcitabine plus cisplatin.

Study Overview

• Status: Completed
• Conditions: Cholangiocarcinoma; Biliary Tract Cancer; HER-2 Gene Amplification; HER-2 Protein Overexpression
• Intervention / Treatment: Drug: Trastuzumab

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 17 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. The subject with disease that is not amendable to a curative treatment approach or locally advanced or metastatic or unresectable CCC with histological diagnosis
2. At least one measurable(per RECIST 1.1) lesion
3. Primary or metastatic tumor with HER2 positive defined on IHC2+, FISH+ or IHC3+
4. ECOG Performance status 0 or 1
5. At least 3 months for life expectancy Common inclusion criteria
6. Men or women over 19 years at time of signing ICF

7. Signed Informed Consent Form

   Exclusion Criteria:

8. Received prior chemotherapy for advanced/metastatic disease (the adjuvant/neoadjuvant chemotherapy completed at least 6 months before enrolled will be accepted)
9. Not recovery from toxicities related to any prior treatments excluding alopecia (eg, neurological toxicity to ≥ Grade 2)
10. History of malignancy other than CCC within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death, such as carcinoma in situ or thyroid papillary carcinoma Hematology, chemistry or organ function
11. ANC < 1.5 × 109/L, or Platelet < 100 × 109/L
12. Total bilirubin > 1.5 × ULN; or AST/ ALT > 2.5 × ULN (or if the tumor has expanded into the liver, > 5 × ULN); or, alkaline phosphatase > 2.5 × ULN (or > 5 × if the tumor has expanded into the liver, or > 10 × ULN if the tumor has expanded into the brain without liver,); or albumin < 2.5 g/dL
13. Creatinine clearance < 60 mL/min(calculated using the Cockcroft-Gault formula) Other exclusion criteria related to IP
14. History of proved congestive heart failure; angina with medication; evidence of transmural myocardial infarction on ECG; uncontrolled hypertension(systolic> 180 mmHg or diastolic> 100 mmHg); clinically significant heart valve disease; uncontrolled arrhythmia
15. LVEF < 50% (calculated by cardiac sonography or MUGA)
16. Subject with rest dyspnea due to metastatic tumor or other disease or who needs oxygen therapy
17. Chronic or high-dose corticosteroid treatment
18. Clinically significant Hearing impairment Common exclusion criteria
19. History or evidence of CNS metastases
20. Interstitial pneumonia or pulmonary fibrosis with symptom and exact lesion on chest X-ray
21. Hearing loss
22. Uncontrolled significant systemic disease (eg, infection or uncontrolled DM)
23. Pregnant or lactating females
24. Sexually active fertile subjects without contraception
25. Treatment with other investigational therapy within 4 weeks prior to initiation of study treatment
26. Radiotherapy within 4 weeks prior to initiation of study treatment (the rest at least 2 weeks after palliative radiotherapy for bone metastasis and recovery from the effects of radiation will be accepted.)
27. Major surgery within 4 weeks prior to initiation of study treatment
28. History of HIV and active HBV or HCV
29. Previously identified allergy or hypersensitivity to components of the study treatment formulations

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Trastuzumab plus Gem/Cis; Gemcitabine 1,000 mg/m2 Day 1 and Day 8, every 3 weeks Cisplatin 25 mg/m2 Day 1 and Day 8, every 3 weeks Trastuzumab, every 3 weeks, 8 mg/kg at first cycle then, 6 mg/kg	Drug: Trastuzumab; Trastuzumab plus gemcitabine/cisplatin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response rate	Best response according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1	6 months
Adverse events	Adverse events graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival	Time between the initiation of chemotherapy and disease progression or death	2 years
Overall survival	Time between the initiation of chemotherapy and any cause of death	2 years

Collaborators and Investigators

• Sponsor: Changhoon Yoo

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2019
• Primary Completion (Actual): November 1, 2020
• Study Completion (Actual): January 4, 2021

Study Registration Dates

• First Submitted: July 28, 2018
• First Submitted That Met QC Criteria: July 28, 2018
• First Posted (Actual): August 2, 2018

Study Record Updates

• Last Update Posted (Actual): January 5, 2021
• Last Update Submitted That Met QC Criteria: January 4, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: Trastuzumab; Cholangiocarcinoma; Biliary Tract Cancer
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Biliary Tract Diseases; Cholangiocarcinoma; Biliary Tract Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Trastuzumab
• Other Study ID Numbers: BTC-HER2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No