A Study of TQB2450 Injection Combined With Anlotinib Hydrochloride Capsule as Second-line Treatment in Subjects With Advanced Biliary Cancer

Phase 3

• Conditions: Advanced Biliary Cancer
• Interventions: Drug: Oxaliplatin injection; Drug: TQB2450 Injection; Drug: Anlotinib hydrochloride; Drug: Capecitabine tablets; Drug: Gemcitabine hydrochloride injection

• Registration Number: NCT04809142
• Lead Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Brief Summary

This study is a randomized, parallel controlled, multicentre phase III clinical trial to evaluate the efficacy and safety of TQB2450 combined with anlotinib versus chemotherapy as second-line treatment in subjects with advanced biliary cancer.

Detailed Description

Not available

Study Timeline

• Study Start: 2021-02-04
• Status Verified: 2021-03
• Study First Submitted: 2021-03-19
• Study First Submitted QC: 2021-03-19
• Last Update Submitted: 2021-03-19
• Study First Posted: 2021-03-22
• Last Update Posted: 2021-03-22
• Primary Completion: 2022-03-18
• Study Completion: 2023-02-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 392

Inclusion Criteria

• 1. Histologically or cytologically confirmed biliary adenocarcinoma, including intrahepatic cholangiocarcinoma (ICC), extrahepatic cholangiocarcinoma (ECC) and gallbladder cancer (GBC).

2.18 years and older,Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1; Life expectancy ≥ 3 months;Weight ≥40 kg or BMI ≥18.5.

3. At least one measurable lesion (based on RECIST 1.1). 4. Previous first-line gemcitabine or fluorouracil-based combination chemotherapy failed.

5.Adequate laboratory indicators. 6. No pregnant or breastfeeding women, and a negative pregnancy test. 7. Understood and Signed an informed consent form.

Exclusion Criteria

• 1. Tumor disease and medical history:

  2. Has central nervous system metastases (CNS) and/or cancerous meningitis or leptomeningeal carcinomatosis;

  3. Has other malignant tumors within 5 years;

  4. Imaging (CT or MRI) shows that tumor invades large blood vessels or the boundary with blood vessels is unclear;

  5. Severe bone damage caused by tumor bone metastasis;

  6. Has uncontrolled and repeated drainage pleural effusion, pericardial effusion, and ascites;

  7. Partial or complete intestinal obstruction and complete biliary obstruction that cannot be relieved; 2. Previous anti-tumor therapy:

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  1. Has received Anlotinib Hydrochloride Capsules, Bevacizumab Injection, and immune checkpoint inhibitors such as PD-1, PD-L1, and CTLA-4 in prior treatment;
  2. Have received anti-tumor therapy within 4 weeks before the first administration;
  3. Unalleviated toxicity ≥ grade 1 due to any previous anticancer therapy; 3.Comorbidities and medical history:
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  1. Active hepatitis B or C;

  2. Kidney abnormalities;

  3. Abnormal thyroid function;

  4. Cardiovascular abnormalities;

  5. Gastrointestinal abnormalities;

  6. History of immunodeficiency;

  7. Has risk of bleeding;

  8. Uncontrollable active bacterial, fungal or viral infections;

  9. Lung diseases, such as interstitial pneumonia, obstructive lung disease, and history of symptomatic bronchospasm;

  10. Allergies to the ingredients of the study drug;

  11. Have a history of neurological or psychiatric disorders

  12. According to the researcher's point of view, other severe, acute or chronic medical or mental illnesses or laboratory abnormalities that may increase the risks associated with participating in the study, or may interfere with the interpretation of the study results;

  13. Have a history of pituitary or adrenal dysfunction

  14. Has received major surgical treatment, open biopsy, or obvious traumatic injury within 28 days before the first administration;

  15. Long-term unhealed wound or fracture;

  16. Has drug abuse history that unable to abstain from or mental disorders; 4. Has participated in other clinical trials within 30 days before the study. 5. Has vaccinated with vaccines or attenuated vaccines within 4 weeks prior to first administration.

      6. Pregnant or breastfeeding women. 7. According to the judgement of the investigators, there are other factors that may lead to the termination of the study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Chemotherapy	Gemcitabine hydrochloride injection	Capecitabine tablets combined with oxaliplatin injection or gemcitabine hydrochloride injection. Each cycle is 3 weeks.
TQB2450+Anlotinib	Anlotinib hydrochloride	TQB2450 1200 mg administered intravenously (IV) on Day 1 of each 21-day cycle ,Anlotinib capsules 12 mg given orally, once daily in 21-day cycle (14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21).
Chemotherapy	Oxaliplatin injection	Capecitabine tablets combined with oxaliplatin injection or gemcitabine hydrochloride injection. Each cycle is 3 weeks.
Chemotherapy	Capecitabine tablets	Capecitabine tablets combined with oxaliplatin injection or gemcitabine hydrochloride injection. Each cycle is 3 weeks.
TQB2450+Anlotinib	TQB2450 Injection	TQB2450 1200 mg administered intravenously (IV) on Day 1 of each 21-day cycle ,Anlotinib capsules 12 mg given orally, once daily in 21-day cycle (14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21).

Primary Outcome Measures

Name	Time	Method
Overall survival (OS)	up to 40 weeks	OS defined as the time from randomization to death from any cause. Participants who do not die at the end of the extended follow-up period, or were lost to follow-up during the study, were censored at the last date they were known to be alive.

Secondary Outcome Measures

Name	Time	Method
Overall response rate (ORR)	up to 24 weeks	Percentage of participants achieving complete response (CR) and partial response (PR).
Duration of response（DOR）	up to 24 weeks	The time when the participants first achieved complete or partial remission to disease progression.
Overall survival at 6 months	up to 6 months	Percentage of participants whose OS has achieved at least 6 months.
Progression free survival (PFS)	up to 24 weeks	PFS defined as the time from randomization until the first documented progressive disease (PD) or death from any cause.
Disease control rate（DCR）	up to 24 weeks	Percentage of participants achieving complete response (CR) and partial response (PR) and stable disease (SD).
Overall survival at 12 months	up to 12 months	Percentage of participants whose OS has achieved at least 12 months.
Progression-free survival at 6 months	up to 6 months	Percentage of participants whose PFS has achieved at least 6 months.

Trial Locations

Locations (17)

Harbin Medical University Affiliated Tumor Hospital; 🇨🇳 Harbin, Heilongjiang, China

Anhui Provincal Hospital; 🇨🇳 Hefei, Anhui, China

Cangzhou Central Hospital; 🇨🇳 Cangzhou, Hebei, China

Beijing Chao-Yang Hospital,Capital Medical University; 🇨🇳 Beijing, Beijing, China

Peking University People's Hospital; 🇨🇳 Beijing, Beijing, China

Beijing Youan Hospital,Captical Medical University; 🇨🇳 Beijing, Beijing, China

Beijing Cancer Hospital; 🇨🇳 Beijing, Beijing, China

Cancer Hospital Chinese Academy of Medical Sciences; 🇨🇳 Beijing, Beijing, China

Beijing Tsinghua Changgung Hospital; 🇨🇳 Beijing, Beijing, China

Fujian Medical University Union Hospital; 🇨🇳 Fuzhou, Fujian, China

Affiliated Hospital of Hebei University; 🇨🇳 Baoding, Hebei, China

Affiliated Hospital of Chengde Medical University; 🇨🇳 Chengde, Hebei, China

Henan Tumor Hospital; 🇨🇳 Zhengzhou, Henan, China

Hunan Provincial People's Hospital; 🇨🇳 Changsha, Hunan, China

The First Peoples Hospital of Changzhou; 🇨🇳 Changzhou, Jiangsu, China

Tongji Medical College of HUST; 🇨🇳 Wuhan, Hubei, China

The First Bethune Hospital of Jilin University; 🇨🇳 Changchun, Jilin, China