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

Biliary Tract Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05065957
• Other study ID #: Inno-GO-05
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: March 29, 2022
• Est. completion date: December 2026

Study information

• Verified date: March 2024
• Source: InnoPharmax Inc.
• Contact: Yuyuan Lin
• Phone: 886-87977607
• Email: yuan.lin[@]innopharmax.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 180
• Est. completion date: December 2026
• Est. primary completion date: July 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Biliary Tract Cancer
• Biliary Tract Neoplasms

Intervention

Drug:
• 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)
• mFOLFOX
intravenous infusion on Day 1 for 14-day cycle

Locations

Country	Name	City	State
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung
Taiwan	China Medical University Hospital	Taichung
Taiwan	National Taiwan University Cancer Center	Taipei
Taiwan	National Taiwan University Hospotal	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei

Sponsors (1)

Lead Sponsor	Collaborator
InnoPharmax Inc.

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of adverse events (AEs)/ serious adverse event (SAEs)	AEs will be assessed via the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03	From date of informed consent to 30-day follow-up visit for each subject
Primary	To assess disease control rate (DCR)	To assess DCR, the percentage of treatment patients who achieved CR, PR, or SD.	From date of randomization until the date of first documented progression, date of death from any cause, or date of withdraw the study for each subject, whichever came first, assessed up to 24 months
Secondary	Phase IIa and IIb: Pharmacokinetics (PK) of gemcitabine (dFdC), difluorodeoxyuridine (dFdU), capecitabine, 5-FU, Tegafur, Gimeracil, and Oteracil potassium	PK parameters (Peak Plasma Concentration (Cmax)) of gemcitabine and Xeloda or TS-1 will be evaluated	Cycle 1 Days 1, 8, and 12 (each cycle is 21 days)
Secondary	Quality of life (QOL) will be assessed using the EORTC questionnaires	To access healthrelated quality of life of cancer patients participating in clinical trial.	Cycle 1 Days 1, and date of withdraw the study (assessed up to 24 months) for each subject (each cycle is 21 days)
Secondary	To assess Progression-free survival (PFS)	To assess PFS, the time from treatment assignment/randomization until objective tumor progression or death	From date of randomization until the date of first documented progression, date of death from any cause, or date of withdraw the study for each subject, whichever came first, assessed up to 24 months
Secondary	To assess Objective response rate (ORR)	To assess ORR, the proportion of treated patients who achieved a BOR of CR or PR.	From date of randomization until the date of first documented progression, date of death from any cause, or date of withdraw the study for each subject, whichever came first, assessed up to 24 months
Secondary	To assess overall survival (OS)	To assess OS, the time from treatment assignment/randomization until death from any case	The survival follow-ups will follow every 6 weeks from date of discontinued study drug for up to 24 months till the death of the subject or closure of the study.