Trastuzumab-pkrb Combined With Modified FOLFOX-6 in Biliary Tract Cancer Patients Progressed on First Line Therapy

A Phase II Trial of Trastuzumab-pkrb Combined With Modified FOLFOX-6 in Biliary Tract Cancer Patients Progressed on First Line Therapy

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 and have shown efficacy in small basket trials. The aim of this study is to evaluate the efficacy and safety of trastuzumab in the combination of mFOLFOX for gemcitabine+cisplatin refractory biliary tract cancer patients.

Study Overview

• Status: Completed
• Conditions: HER2 Positive Advanced/Metastatic/Nonresectable Biliary Tract Cancer
• Intervention / Treatment: Drug: HERZUMA+mFOLFOX

Detailed Description

This phase II study is designed to see whether trastuzumab-pkrb+FOLFOX is active as 2nd or 3rd line treatment for HER2-positive biliary tract cancer patients.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 2

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Division of Medical Oncology, Yonsei Cancer Center, Yonsei Univ. College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Histologically documented recurred/metastatic/unresectable biliary tract cancer, including gallbladder cancer, intrahepatic, extrahepatic cholangiocarcinoma, or ampulla of vater cancer.
2. Histologically confirmed HER2 positive biliary tract cancer. HER2-positive tumor was defined as either IHC 3+ or IHC 2+ in combination with ISH +, or ERBB2 amplification (≥6 copies) by tumor tissue NGS.
3. Recurred/metastatic/unresectable biliary tract cancer patient whose disease progression was confirmed by imaging modality after gemcitabine+cisplatin containing 1st line palliative chemotherapy regimen. Previous lines should be one or two (immunotherapy monotherapy not counted).
4. be willing and able to provide written informed consent/assent for the trial
5. be at least 19 years of age on day of signing informed consent
6. have measurable disease based on RECIST (Response Evaluation Criteria In Solid Tumors) version 1.1
7. have a performance status of 0 or 1 on the ECOG (Eastern Cooperative Oncology Group) Performance Scale
8. demonstrate adequate organ function
9. No severe valvular or arrhythmic cardiac disease with LVEF ≥ 50%
10. female subject of childbearing potential should have a negative urine or serum pregnancy or be willing to use birth control

Exclusion Criteria:

1. Previous treatment history of oxaliplatin containing chemotherapy, anti-HER2 targeting treatment (trastuzumab, neratinib, lapatinib, and etc)
2. has had a prior anti-cancer chemotherapy, targeted small molecule therapy, or radiotherapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered.
3. has a known additional malignancy that is progressing or requires active treatment within 3 years, except basal cell carcinoma of the skin, squamous cell carcinoma of the skin and thyroid cancer that has undergone potentially curative therapy or in situ cervical cancer
4. has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
5. has known history or evidence of any disease, treatment, or laboratory results that would inhibit the patient's participation to the study.
6. Has clinically significant cardiac disease, including congestive heart failure ≥ NYHA grade 2, uncontrolled hypertension, QTcF > 470 msec or QT prolong syndrome, recent myocardiac infarction or unstable angina history
7. has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
8. is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment
9. has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)
10. has known active Hepatitis B (HBsAg reactive and HBV DNA 100 ≥copies/ml) or Hepatitis C (anti-HCV reactive and HCV RNA [qualitative] is detected)
11. has received a live vaccine within 30 days of planned start of study therapy.
12. has an active infection requiring systemic therapy
13. has history of severe adverse event or allergic reaction to 5-FU, leucovorin, oxaliplatin or trastuzumab
14. need O2 supply or show dyspnea on rest due to advanced malignancy

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: HERZUMA+mFOLFOX	Drug: HERZUMA+mFOLFOX; Herzuma (Trastuzumab-pkrb) 4mg/kg after 6mg/kg loading D1 5FU 400mg/m2 bolus+2400mg/m2 infusion for 46 hrs D1 Leucovorin 200mg/m2 D1 Oxaliplatin 85mg/m2 D1 every 2 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR)	rate of patients with complete remission (CR) or partial remission (PR) based on RESIST1.1.	up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	PFS is defined as time interval from cycle 1 day 1 to tumor progression/death/last follow-up	up to 2 years
Disease control rate (DCR)	DCR is rate of patients with CR, PR, or SD per RECIST 1.1.	up to 2 years
Overall survival (OS)	OS is defined as time interval from cycle 1 day 1 to tumor death/last follow-up.	up to 2 years
Incidence of treatment related adverse events (TRAE)	Incidence of treatment related adverse events (TRAE) will be assessed using NCI CTCAE v5.0 and tabulated and reported.	up to 2 years

Collaborators and Investigators

• Sponsor: Yonsei University
• Investigators: Principal Investigator: Choong-kun Lee, Severance Hospital

Publications and helpful links

General Publications

• Lee CK, Chon HJ, Cheon J, Lee MA, Im HS, Jang JS, Kim MH, Park S, Kang B, Hong M, Kim JW, Park HS, Kang MJ, Park YN, Choi HJ. Trastuzumab plus FOLFOX for HER2-positive biliary tract cancer refractory to gemcitabine and cisplatin: a multi-institutional phase 2 trial of the Korean Cancer Study Group (KCSG-HB19-14). Lancet Gastroenterol Hepatol. 2023 Jan;8(1):56-65. doi: 10.1016/S2468-1253(22)00335-1. Epub 2022 Oct 31.

Study record dates

Study Major Dates

• Study Start (Actual): June 23, 2020
• Primary Completion (Actual): June 14, 2023
• Study Completion (Actual): June 14, 2023

Study Registration Dates

• First Submitted: January 19, 2021
• First Submitted That Met QC Criteria: January 19, 2021
• First Posted (Actual): January 25, 2021

Study Record Updates

• Last Update Posted (Actual): October 11, 2023
• Last Update Submitted That Met QC Criteria: October 10, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: HER2; trastuzumab; biliary tract cancer; herzuma
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Digestive System Neoplasms; Biliary Tract Diseases; Biliary Tract Neoplasms
• Other Study ID Numbers: 4-2019-0648

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