Combination therapy for advanced biliary tract cancer

Open-Label, Multicenter, Phase II/III Study of Combination Therapy of D07001-Softgel Capsules and Xeloda/TS-1 in Subjects With Advanced Biliary Tract Cancer After Gemcitabine and Cisplatin-Based Treatment Failure

This study is testing a new combination of D07001-softgel capsules with existing cancer treatments to see if it can help people with advanced biliary tract cancer feel better and improve their outcomes.

Quick facts

• Phase: Phase2; Phase3
• Study type: Interventional
• Enrollment: 180 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: InnoPharmax Inc. (Industry-sponsored)
• Drugs / interventions: chemotherapy, radiation
• Locations: 5 sites (Kaohsiung City and 4 other locations)
• Trial ID: NCT05065957 on ClinicalTrials.gov

What this trial studies

This open-label, multicenter clinical trial evaluates the safety and efficacy of D07001-softgel capsules combined with Xeloda or TS-1 in patients with advanced biliary tract cancer. The study consists of two phases: a dose-finding phase (Phase IIa) to identify the optimal dose and a dose-expansion phase (Phase IIb/III) where patients are randomized to receive either the combination therapy or mFOLFOX treatment. The primary outcome measures include safety assessments and disease control rate (DCR). An adaptive interim analysis will guide the continuation or modification of the study based on initial results.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 years or older with unresectable metastatic or locally advanced biliary tract cancer who have failed first-line gemcitabine and cisplatin-based chemotherapy.

Not a fit: Patients with resectable biliary tract cancer or those who have not received prior chemotherapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this combination therapy could provide a new treatment option for patients with advanced biliary tract cancer who have not responded to first-line chemotherapy.

How similar studies have performed: While this approach is novel, similar combination therapies have shown promise in other cancer types, indicating potential for success.

Eligibility criteria

Inclusion Criteria:

1. Male or female patients aged 18 years or older at screening (aged 20 years or older in Taiwan)
2. Histopathological or cytologic diagnosis of unresectable metastatic or locally advanced BTC (cholangiocarcinoma, gallbladder cancer or ampullary carcinoma)
3. Subject must have failed from first line gemcitabine and cisplatin-based chemotherapy
4. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0-1
5. Life expectancy is \>12 weeks
6. Adequate bone marrow function, demonstrated by:

   1. Absolute neutrophil count (ANC) ≥1,500 cell/mm3
   2. Platelet count ≥ 100,000 cells/mm3
   3. Hemoglobin ≥ 9 g/dL
7. Adequate liver function, demonstrated by:

   1. Aspartate transaminase (AST) and alanine transaminase (ALT) ≤2.5 x upper limit of normal (ULN), or ≤5.0 x ULN in the case of liver metastases
   2. Total bilirubin ≤1.5 x ULN
   3. Albumin ≥3.0 g/dL
   4. International normalized ratio (INR) \<1.5
8. Adequate renal function, demonstrated by:

   1. Serum creatinine ≤1.5 x ULN
   2. Creatinine clearance ≥ 50mL/min calculated by Cockcroft-Gault formula or eGFR ≥ 50mL/min/1.73m2 by 2021 CKD-EPI Creatinine Equation
9. A negative serum pregnancy test at screening and is not breastfeeding in woman of childbearing potential
10. Women of childbearing potential or male subjects must use a medically acceptable form of contraception as 2 barrier methods (e.g., combination of condom, diaphragm, or intrauterine device), hormonal contraception (estrogen or progesterone agents) or 1 barrier method in combination with spermicide. Birth control is required 1 month prior to screening, for the duration of their study participation, and for 1 month after the end of the study; female partners of male subjects must adhere to the same birth control methods.
11. Provision of a signed and dated written Informed Consent Form (ICF) prior to any study specific procedures
12. Subject is willing to comply with protocol-required visit schedule and visit requirements
13. No more than 60 days have elapsed between completion of the prior line of chemotherapy or CCRT and enrollment
14. Subject has not received other chemotherapy since first-line treatment

Exclusion Criteria:

1. Have prior chemotherapy regimen other than first line gemcitabine and cisplatin-based therapy for unresectable metastatic or locally advanced BTC Note: prior fluoropyrimidine base (including capecitabine, carmofur (HCFU), doxifluridine, fluorouracil (5-FU), and tegafur) chemotherapy (including fluoropyrimidine monotherapy or combination therapy) are allowed as postsurgical adjuvant therapy.
2. Diagnosis of active malignancy other than BTC within the past 2 years, except nonmelanoma skin carcinoma and carcinoma-in-situ of uterine cervix treated with curative intent
3. Prior discontinuation of gemcitabine because of pulmonary or hepatic toxicity or hemolytic uremic syndrome (HUS) or hypersensitivity, allergic reaction, or intolerance
4. Known or suspected hypersensitivity to capecitabine, tegafur, gimeracil, oteracil potassium, oxaliplatin or other platinum compounds, leucovorin products, folic acid or folinic acid, 5-fluorouracil or their excipients.
5. Prior discontinuation of fluoropyrimidine because of any unexpected or severe reaction.
6. Treatment with brivudine, sorivudine, or its chemically-related analogs ≤ 28 days prior to the date of enrollment.
7. Under flucytosine treatment.
8. Residual toxicity from prior chemotherapy or CCRT that is Grade ≥2 (residual Grade 2 neuropathy and alopecia are permitted)
9. Any GI disorder which would significantly impede absorption of an oral agent
10. Known brain or leptomeningeal metastases
11. Major surgery or definitive ablation-intent (excluding palliative radiotherapy for bone metastasis) radiation therapy within the past 28 days
12. Any active disease or condition that would not permit compliance with the protocol
13. Clinically significant cardiovascular disease (e.g., uncontrolled hypertension, unstable angina, congestive heart failure, or New York Heart Association \[NYHA\] Grade 2 or greater), or uncontrolled serious cardiac arrhythmia
14. Have documented cerebrovascular disease. Subjects with the disease may be excluded, but if the investigator assesses that they are asymptomatic or well controlled could be enrolled.
15. Have a seizure disorder not controlled on medication (based on decision of Investigator)
16. Received an investigational agent within 28 days of enrollment
17. Have an uncontrolled active viral, bacterial, or systemic fungal infection
18. Known human immunodeficiency virus (HIV) infection
19. Have HBsAg (hepatitis B surface antigen) positive with HBV-DNA ≥2000 copies/ml and/or anti-HCV antibody (HCV) positive with HCV-RNA positive.
20. Received yellow fever vaccine or other live attenuated vaccine(s) within the 4 weeks prior to screening
21. History of drug or alcohol abuse within last year
22. Have any other serious medical condition that, in the Investigator's medical opinion, would preclude safe participation in, and compliance with, a clinical trial

Where this trial is running

Kaohsiung City and 4 other locations

• Kaohsiung Medical University Chung-Ho Memorial Hospital — Kaohsiung City, Taiwan (Recruiting)
• China Medical University Hospital — Taichung, Taiwan (Recruiting)
• National Taiwan University Cancer Center — Taipei, Taiwan (Recruiting)
• National Taiwan University Hospotal — Taipei, Taiwan (Recruiting)
• Taipei Veterans General Hospital — Taipei, Taiwan (Recruiting)

Study contacts

• Principal investigator: Li-Tzong Chen, Ph.D — National Institute of Cancer Research
• Study coordinator: Yuyuan Lin

Conditions Biliary Tract Cancer