Actively Recruiting
First-line Trastuzumab, Gemcitabine, Cisplatin and Nivolumab in Advanced HER2- Positive Biliary Tract Cancer: a Multicenter, Open-label, Single-arm Phase Ib/II Trial (HERBOT)
Led by Yonsei University · Updated on 2025-02-05
44
Participants Needed
1
Research Sites
198 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Biliary tract cancer is a rare malignant neoplasm including intrahepatic cholangiocarcinoma (IhCCA), extrahepatic cholangiocarcinoma (EhCCA) and Gallbladder cancer (GBC). Survival outcome of advanced BTCs are still poor and heterogeneity of tissue and molecular differences between BTCs limit the clinical studies in BTCs. Combination therapy of Gemcitabine and Cisplatin has become the standard of care after the ABC-02 trial. This trial demonstrated that the addition of cisplatin to gemcitabine improved survival outcomes compared to that with gemcitabine alone. However, the median overall survival (OS) of Gem/Cis chemotherapy is only about one year. Anti-Program cell death-1 (anti-PD-1) inhibitor monotherapy including Nivolumab (OPDIVO) had shown efficacy in refractory, advanced BTC. Various ICIs combined with Gem/Cis as the 1st line treatment in BTCs are under the trials. Combination of Nivolumab and Gem/Cis showed improved overall survival (15.4 months) in a small sized study (n=30) with tolerable side effects in advanced BTC patients. Recently reported interim analysis of phase III TOPAZ-1 trial (NCT03875235) showed Durvalumab, anti-PD-L1 agent, combined with Gem/Cis showed improvement of overall survival. Considering other studies currently ongoing, ICIs combined with Gem/Cis are thought to be the future standard of care in 1st line treatment of advanced stage BTCs. HER2 amplification/overexpression is presented as many as 15% of total BTC patients. Basket trial of administration of pertuzumab and trastuzumab combination in previously treated HER2 positive advanced BTC patients showed promising overall response rate of 23%. Also, multicenter phase II study conducted by Korean investigators (KCSG-HB19-14) showed promising effect of Trastuzumab combined with modified FOLFOX in Gem/Cis refractory HER2 positive BTC patients with ORR of 29.4%. Moreover, preclinical data showed synergistic anti-cancer effect of trastuzumab combined with ICIs in HER2 positive cancers. Similar data are reported in HER2 positive gastric cancer that phase II and phase III clinical data showed 1st-line ICIs combined with trastuzumab and cytotoxic chemotherapy showed promising overall survival outcomes. In treating HER2-positive advanced BTC, the triple combination of nivolumab, trastuzumab, and cytotoxic chemotherapy (Gem/Cis) may overcome innate resistance and activate an immune response to cancer along with inhibiting oncogenic signal from HER2 pathway, resulting in a synergistic effect with a longer response.
CONDITIONS
Official Title
First-line Trastuzumab, Gemcitabine, Cisplatin and Nivolumab in Advanced HER2- Positive Biliary Tract Cancer: a Multicenter, Open-label, Single-arm Phase Ib/II Trial (HERBOT)
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Histologically or cytologically confirmed biliary tract cancer including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, or gallbladder cancer
- HER2-positive biliary tract cancer defined as IHC 3+ or IHC 2+ with positive ISH or ERBB2 gene copy number ≥ 6.0 by NGS
- Age 20 years or older at informed consent
- Previously untreated for unresectable or metastatic disease at diagnosis, or recurrent disease more than 6 months after curative surgery or adjuvant therapy
- Signed informed consent form
- Measurable lesions according to RECIST v.1.1
- ECOG Performance Status score of 0 or 1
- Life expectancy of at least 3 months
- Adequate laboratory values within 14 days before enrollment (specific blood counts, liver and kidney function, coagulation)
- Women of childbearing potential must agree to use contraception during and after treatment and not breastfeed
- Men must agree to use contraception during and after treatment
- Left ventricular ejection fraction ≥ 50% by echocardiography or MUGA scan
- Willingness to provide tumor biopsy tissue
- Adequate organ function
You will not qualify if you...
- Previous systemic chemotherapy, biologic therapy, immunotherapy, hormone therapy, or clinical trial treatment for advanced biliary tract cancer, except permitted prior adjuvant chemotherapy or one cycle of gemcitabine-based chemotherapy
- Multiple primary cancers except certain fully resected or non-recurrent cancers
- Residual side effects from prior treatments affecting safety
- History or current severe hypersensitivity to antibody products
- Autoimmune diseases or history of chronic/recurrent autoimmune disease
- History or current interstitial lung disease or pulmonary fibrosis
- Symptomatic diverticulitis or gastrointestinal ulcer disease
- Symptomatic or treated brain or meningeal metastases
- Pericardial fluid, pleural effusion, or ascites requiring treatment
- Uncontrollable tumor-related pain
- Transient ischemic attack or stroke within 180 days before enrollment
- Significant uncontrolled cardiovascular disease
- Uncontrollable diabetes mellitus
- Active infections requiring treatment
- Recent use of systemic corticosteroids or immunosuppressants
- Recent antineoplastic or radiotherapy treatments within specified timeframes
- Positive HIV, HTLV-1, hepatitis B or C tests unless controlled
- Pregnant or breastfeeding women
- Recent use of unapproved drugs
- Prior treatment with Nivolumab or similar immune therapies
- Inability to provide informed consent
- Other investigator-determined contraindications
- History of hypersensitivity to Nivolumab
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Trial Site Locations
Total: 1 location
1
Severance Hospital, Yonsei University Health System
Seoul, South Korea
Actively Recruiting
Research Team
C
Choong-kun Lee
CONTACT
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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