Study of Combination Therapy of D07001-Softgel Capsules and Xeloda/TS-1 in Subjects With Advanced Biliary Tract Cancer

NCT ID: NCT05065957

Last Updated: 2025-04-30

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 180 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-29
• Study Completion Date: 2026-12-31

Brief Summary

The primary objective are:

To assess the safety and tolerability of the combination of D07001-softgel capsules and Xeloda/TS-1.

To evaluate the efficacy of the combination of D07001-softgel capsules and Xeloda/TS-1, as assessed by disease control rate (DCR).

Detailed Description

This open label, multicenter study will be conducted in 2 stages: a dose-finding stage (Phase IIa) and a dose-expansion stage (Phase IIb/III).

In phase IIa, eligible patients will be assigned to receive oral D07001-softgel on Days 1, 3, 5, 8, 10, 12, 15, 17, and 19 of a 21-day cycle (9 doses per cycle) and Xeloda (or TS-1) twice daily on Day 1-14 of a 21-day cycle.

A modified 3+3 dose-finding design method will be applied to identify dose-limiting toxicities (DLTs) and establish the selected dose of D07001-softgel capsules plus Xeloda (or TS-1).

In phase IIb/III,the first 40 subjects (20 subjects per arm) will be randomly allocated in a 1:1 ratio in two arms. Arm A will receive active symptom control (ASC) with the selected dose from dose-finding stage of D07001-softgel capsules and Xeloda (or TS-1), in 21-day cycles. In arm B, subjects will receive ASC with mFOLFOX treatment. After the last subject of first 40 subjects will be completed the visit in the end of treatment, an adaptive interim analysis will be planned to re-estimate the required sample size based on the result of DCR if needed. The sponsor team will determine whether the study will be continued or stopped for futility.

If the study continues to proceed, the total subject number will be based on the decision from the results of interim study. The rest of subjects will be randomized to receive the combination of study drug or active-control drug with the same allocation in two arms. Both groups will continue the therapy until disease progression, withdrawn consent, or when another treatment discontinuation criterion is met.

Conditions

Biliary Tract Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase IIa:Dose-Finding Stage

Level -5: 20 mg D07001-softgel capsules plus 625 mg/m^2 Xeloda (or 20/30/40 mg TS-1).

Level -4: 40 mg D07001-softgel capsules plus 625 mg/m^2 Xeloda (or 20/30/40 mg TS-1).

Level -3: 60 mg D07001-softgel capsules plus 625 mg/m^2 Xeloda (or 20/30/40 mg TS-1).

Level -2: 80 mg D07001-softgel capsules plus 625 mg/m^2 Xeloda (or 20/30/40 mg TS-1).

Level -1 (starting dose): 100 mg D07001-softgel capsules plus 625 mg/m^2 Xeloda (or 20/30/40 mg TS-1).

Level 1: 100 mg D07001-softgel capsules plus 800 mg/m^2 Xeloda (or 30/40/50 mg TS-1).

Level 2: 100 mg D07001-softgel capsules plus 1000 mg/m^2 Xeloda (or 40/50/60 mg TS-1).

Group Type: EXPERIMENTAL

D07001-softgel capsules + Xeloda (or TS-1)

Intervention Type: DRUG

D07001-softgel capsules: 3 times per week (on Days 1, 3, 5, 8, 10, 12, 15, 17, and 19 of a 21-day cycle, 9 doses per cycle).

Xeloda (or TS-1): twice daily for 14 consecutive days followed by 7 days rest (1 treatment cycle)

Phase IIb/III: Dose Expansion Stage

ASC+ D07001-softgel capsules plus Xeloda (or TS-1)

ASC+mFOLFOX (5-FU+Oxalipatin+folinic acid)

Group Type: ACTIVE_COMPARATOR

D07001-softgel capsules + Xeloda (or TS-1)

Intervention Type: DRUG

D07001-softgel capsules: 3 times per week (on Days 1, 3, 5, 8, 10, 12, 15, 17, and 19 of a 21-day cycle, 9 doses per cycle).

Xeloda (or TS-1): twice daily for 14 consecutive days followed by 7 days rest (1 treatment cycle)

mFOLFOX

Intervention Type: DRUG

intravenous infusion on Day 1 for 14-day cycle

Interventions

D07001-softgel capsules + Xeloda (or TS-1)

D07001-softgel capsules: 3 times per week (on Days 1, 3, 5, 8, 10, 12, 15, 17, and 19 of a 21-day cycle, 9 doses per cycle).

Xeloda (or TS-1): twice daily for 14 consecutive days followed by 7 days rest (1 treatment cycle)

Intervention Type: DRUG

mFOLFOX

intravenous infusion on Day 1 for 14-day cycle

Intervention Type: DRUG

Other Intervention Names

Treatment group; Control group

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

InnoPharmax Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Li-Tzong Chen, Ph.D

Role: PRINCIPAL_INVESTIGATOR

National Institute of Cancer Research

Locations

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, , Taiwan

Site Status: RECRUITING

China Medical University Hospital

Taichung, , Taiwan

Site Status: RECRUITING

National Taiwan University Cancer Center

Taipei, , Taiwan

Site Status: RECRUITING

National Taiwan University Hospotal

Taipei, , Taiwan

Site Status: RECRUITING

Taipei Veterans General Hospital

Taipei, , Taiwan

Site Status: RECRUITING

Countries

Taiwan

Central Contacts

Yuyuan Lin

Role: CONTACT

yuan.lin@innopharmax.com

886-87977607 ext. 211

Facility Contacts

Li-Tzong Chen, M.D.

Role: primary

Li-Yuan Bai, M.D.

Role: primary

Chiun Hsu, M.D.

Role: primary

Tsung-hao Liu, M.D.

Role: primary

Ming-Huang Chen, M.D.

Role: primary

Other Identifiers

Inno-GO-05

Identifier Type: -

Identifier Source: org_study_id