A Trial Evaluating Surufatinib Efficacy and Safety in Biliary Tract Carcinoma Patients

NCT03873532 | Unknown Phase 2 DMC

• 1 other identifier: 2017-012-00CH2
• Study Type: interventional
• Target: 298
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, open-label, active-control, multi-center, phase IIb/III clinical study to evaluate the efficacy and safety of surufatinib vs. Capecitabine as a second-line therapy in patients with unresectable or metastatic biliary tract cancer (BTC). About 298 subjects are randomly assigned to two study treatment groups in the ratio of 1:1 by Interactive Web Response System (IWRS).

• Active group: 300 mg of surufatinib，once a day for 3 weeks as a cycle;
• Control group: In each 3-week cycle, Capecitabine is given at 1250 mg/m2 by oral administration twice a day for 2 weeks, followed by 1 week rest period (equivalent to 2500 mg/m2 total daily dose). All patients will be treated based on the arm to which they have been randomized. Treatment on study will continue until disease progression, death, intolerable toxicity or other criteria for discontinuation from study treatment. The tumor assessments are performed with imaging every 6 weeks (+3 days) until progressive disease (RECIST v1.1) or death on the study treatment period, and the treatment and survival of the patients after progressive disease are recorded. Safety indicators include adverse events, laboratory tests, vital signs, and changes in electrocardiograms and echocardiograms.

Conditions

Biliary Tract Cancer

Outcome Measures

Primary Outcomes (1)

• Overall survival (OS)

  Compare the Overall survival (OS) rate between surufatinib group and Capecitabine group.

  5 months after the last patient enrolled.

Secondary Outcomes (4)

• Progression-free survival (PFS)

  5 months after the last patient enrolled.

• Objective remission rate (ORR)

  5 months after the last patient enrolled.

• Disease control rate (DCR)

  5 months after the last patient enrolled.

• Duration of response (DOR)

  5 months after the last patient enrolled.

Other Outcomes (3)

• Quality of life score

  5 months after the last patient enrolled.

• Changes of tumor markers (CEA, CA199)

  5 months after the last patient enrolled.

• Detection of biomarkers

  5 months after the last patient enrolled.

Study Arms (2)

Active group

EXPERIMENTAL

300 mg of surufatinib is given by oral administration once a day (QD) every 3 weeks;

Drug: Surufatinib

Control group

ACTIVE COMPARATOR

In each 3-week cycle, Capecitabine is given at 1250 mg/m2 by oral administration twice a day (BID) for 2 weeks, followed by 1 week rest period (equivalent to 2500 mg/m2 total daily dose).

Drug: Capecitabine

Interventions

Surufatinib DRUG

Patients receive oral Surufatinib at a dose of 300mg/d within 1 hour after breakfast (once-daily dosing continuously, every 21-day treatment cycle).

Also known as: HMPL-012 and Sulfatinib

Active group

Capecitabine DRUG

Capecitabine is given at 1250 mg/m2 by oral administration twice a day (BID, one dose each in the morning and evening, with a total dose of 2500 mg/m2 per day) for 2 weeks followed by 1 week of drug interruption. Each course of treatment will last 3 weeks. Capecitabine tablets should be swallowed with water within 30 minutes after a meal.

Also known as: Xeloda

Control group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients are fully informed about the study and voluntarily sign the informed consent (prior to the implementation of any specific procedure for the trial);
• years old (inclusive);
• Patients with histologically or cytologically confirmed unresectable or metastatic BTC, including intrahepatic cholangiocarcinoma (IHCC), extrahepatic cholangiocarcinoma (EHCC) and gallbladder cancer (GBC);
• Patients have failed first-line standard systemic chemotherapy. A first-line standard systemic chemotherapy is defined as a regimen of gemcitabine combined with platinum-based therapy. The failure of a first-line standard chemotherapy is defined by progressive disease during the treatment or within 6 months after the last treatment, or intolerable toxicity during the treatment.
• Note: a. The time of first-line medication is ≥ 1 cycle of combination chemotherapy; b. Neoadjuvant or adjuvant chemotherapy is allowed in the early stage, and should be considered failed as a first-line systemic chemotherapy for progressive disease if progressive disease/recurrence occurs during the course of the neoadjuvant/adjuvant therapy or within 6 months after the end of treatment; c. The previous first-line standard chemotherapy does not contain any small molecular anti-angiogenesis agents or monoclonal antibodies, or any drugs related to tumor immunity;
• ECOG performance status of 0 or 1 (Annex 1);
• Liver function with a modified Child-Pugh score of \< 7;
• Confirmed measurable (or evaluable) lesions that meet the requirements of RECIST 1.1;
• Expected survival of ≥ 12 weeks;
• Fertile male or female patients shall volunteer to use effective contraceptive methods, such as double barrier contraception, condoms, oral or injected contraceptives, and intrauterine devices, during the study period and within 90 days after the last dosing of the investigational drug. All female patients will be considered fertile unless they have had natural menopause, or artificial menopause or sterilization (such as hysterectomy, bilateral adnexectomy or ovarian radiation).

You may not qualify if:

• Received a systemic anti-cancer therapy that has been approved or in development, including chemotherapy, radical radiotherapy, bio-immunotherapy, targeted therapy, and treatment by traditional Chinese medicines (if the instructions of the traditional Chinese medicines specifies clear indications for anti-tumor therapy, the patient may be enrolled after an 1 week of washout period), within 4 weeks prior to randomization;
• Received a systemic chemotherapy (a neoadjuvant or adjuvant chemotherapy except those that have not failed within 6 months) other than gemcitabine combined with platinum-based therapy (such as fluorouracil-based chemotherapy) prior to randomization; or received an anti-tumor immunotherapy, such as PD-1 and PD-L1 therapies;
• Received any surgery or invasive treatment/operation (except venous catheterization, puncture and drainage, etc) within 4 weeks prior to randomization;
• Received any major surgical operations within 60 days before randomization, or have any incisions that have not completely healed;
• Received a local anti-tumor therapy such as hepatic artery interventional embolization, cryoablation of liver metastases, or radiofrequency ablation within 4 weeks prior to randomization;
• Patients with any of the following laboratory abnormalities:
• Absolute neutrophil count (ANC) \< 1.5 × 109/L, or platelet (PLT) \< 100 × 109/L, or hemoglobin (Hb) \< 90 g/L;
• Total bilirubin ≥ 1.5 × Upper Limit of Normal (ULN);
• In the absence of liver metastasis, alanine transaminase (ALT) and/or aspartate transaminase (AST) ≥ 1.5 × ULN; in the presence of liver metastasis, ALT and/or AST ≥ 3 × ULN;
• Serum creatinine ≥ 1.5 × ULN or creatinine clearance \< 50 mL/min (calculated according to the Cockcroft-Gault formula, as shown in Annex 2);
• Routine urinalysis shows urinary protein of ≥ 2+ or 24-hours urinary protein of ≥ 1 g;
• Uncontrolled malignant ascites (ascites that cannot be controlled by diuretics or puncture as judged by the investigator);
• Liver metastases accounting for half or more of the total liver volume as determined by the investigator;
• International normalized ratio (INR) \> 1.5 or activated partial thromboplastin time (APTT) \> 1.5 × ULN;
• Clinically significant electrolyte abnormalities as determined by the investigator;

Sponsors & Collaborators

• Hutchison Medipharma Limited: lead

Study Sites (1)

PLA 307 Hospital

Beijing, Beijing Municipality, 100000, China

RECRUITING

MeSH Terms

Conditions

Biliary Tract Neoplasms

Interventions

surufatinib; Capecitabine

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Rongjun Liu

  Hutchison Medipharma Limited

  STUDY DIRECTOR

Central Study Contacts

Xuefeng Zhao

CONTACT

+86 21 20673222; xuefengz@hmplglobal.com

Rongjun Liu

CONTACT

+86 21 20673203; rongjunl@hmplglobal.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 12, 2019
• First Posted: March 13, 2019
• Study Start: July 10, 2018
• Primary Completion: June 1, 2021
• Study Completion: March 1, 2022
• Last Updated: February 13, 2020

Record last verified: 2020-02

Locations

CN (1)