Clinical trial NCT04722133: Trastuzumab-pkrb Combined With Modified FOLFOX-6 in Biliary Tract Cancer Patients Progressed on First Line Therapy
Official title: A Phase II Trial of Trastuzumab-pkrb Combined With Modified FOLFOX-6 in Biliary Tract Cancer Patients Progressed on First Line Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HER2 Positive Advanced/Metastatic/Nonresectable Biliary Tract Cancer
Keywords: biliary tract cancer
HER2
herzuma
trastuzumab
Lead sponsor: Yonsei University
Sponsor class: OTHER
First posted: 2021-01-25
Enrollment: 36
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Objective response rate (ORR)
timeFrame: up to 2 years
Secondary outcomes:
measure: Progression-free survival (PFS)
timeFrame: up to 2 years
measure: Disease control rate (DCR)
timeFrame: up to 2 years
measure: Overall survival (OS)
timeFrame: up to 2 years
measure: Incidence of treatment related adverse events (TRAE)
timeFrame: up to 2 years
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Division of Medical Oncology, Yonsei Cancer Center, Yonsei Univ. College of Medicine
Study officials:
affiliation: Severance Hospital
name: Choong-kun Lee
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.