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A Study to Investigate Sitravatinib as Monotherapy and in Combination With Tislelizumab in Patients With Unresectable Locally Advanced or Metastatic HCC or GC/GEJC

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ClinicalTrials.gov Identifier: NCT03941873
Recruitment Status : Recruiting
First Posted : May 8, 2019
Last Update Posted : November 18, 2019
Sponsor:
Information provided by (Responsible Party):
BeiGene

Brief Summary:
The purpose of this study is to evaluate the safety,tolerability, pharmacokinetics and preliminary antitumor activity of sitravatinib as monotherapy and in combination with tislelizumab in patients with unresectable locally advanced or metastatic hepatocellular carcinoma or gastric/gastroesophageal junction cancer.

Condition or disease Intervention/treatment Phase
Carcinoma, Hepatocellular Gastric/Gastroesophageal Junction Cancer Drug: Sitravatinib Drug: Sitravatinib plus Tislelizumab Drug: Sitravatinib and tislelizumab Phase 1 Phase 2

Detailed Description:

This is an open-label, multicenter Phase 1/2 clinical study for patients with histologically or cytologically confirmed unresectable locally advanced or metastatic HCC or G/GEJ cancer. All patients will receive study treatment (s) until PD, unacceptable toxicity, death, withdrawal of consent, or study termination by sponsor. This study consists of the following phases.

Phase 1 (Dose escalation for sitravatinib as monotherapy and in combination with tislelizumab): Two dose levels of sitravatinib as monotherapy, 80 mg once daily and 120 mg once daily, will be evaluated in patients with unresectable locally advanced or metastatic HCC or G/GEJ cancer. A modified 3+3 design will be used in the dose escalation. Approximately 6 to 12 evaluable patients will be treated with sitravatinib as monotherapy. The combination dose escalation of sitravatinib (80 mg once daily and 120 mg once daily; modified 3+3 design) with tislelizumab (200 mg every 3 weeks, in both cohorts) will be evaluated in patients with unresectable locally advanced or metastatic HCC or G/GEJ cancer.

Phase 2 (Dose expansion for sitravatinib as monotherapy and in combination with tislelizumab): Approximately 20 patients will be enrolled in each cohort. There will be a total of 4 cohorts in the study.

  • Cohort A: Anti-PD-1/PD-L1 antibody naive HCC
  • Cohort B: Anti-PD-1/PD-L1 antibody naive HCC
  • Cohort C: Anti-PD-1/PD-L1 antibody refractory/resistant HCC
  • Cohort D: Anti-PD-1/PD-L1 antibody naive G/GEJ cancer

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 104 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of Sitravatinib as Monotherapy and in Combination With Tislelizumab in Patients With Unresectable Locally Advanced or Metastatic HCC or GC/GEJC
Actual Study Start Date : February 28, 2019
Estimated Primary Completion Date : August 2020
Estimated Study Completion Date : July 2021

Arm Intervention/treatment
Experimental: Sitravatinib monotherapy
Two dose levels of sitravatinib as monotherapy, 80 mg once daily and 120 mg once daily, will be evaluated in patients with unresectable locally advanced or metastatic HCC or G/GEJ cancer. A modified 3+3 design will be used in the dose escalation to confirm RP2D.
Drug: Sitravatinib
Study subjects will receive sitravatinib capsule once daily

Experimental: Sitravatinib plus Tislelizumab
The combination dose escalation of sitravatinib (80 mg once daily and 120 mg once daily; modified 3+3 design) with tislelizumab (200 mg every 3 weeks, in both cohorts) will be evaluated in unresectable locally advanced or metastatic HCC or G/GEJ cancer patients . If the combination dose of 80 mg sitravatinib and 200 mg tislelizumab has been declared tolerable, the dose of sitravatinib will be escalated to 120 mg and tislelizumab will remain fixed at 200 mg. Approximately 6 to 12 evaluable patients will be treated. The dose of tislelizumab during dose escalation for the combination will be kept fixed at 200 mg.
Drug: Sitravatinib plus Tislelizumab
Study subjects will receive sitravatinib capsule once daily and in combination with tislelizumab IV once every 3 weeks.

Experimental: Anti-PD-1/PD-L1 antibody naïve HCC(Monotherapy) Drug: Sitravatinib
Study subjects will receive sitravatinib capsule once daily.

Experimental: Anti-PD-1/PD-L1 antibody naive HCC(Combination) Drug: Sitravatinib and tislelizumab
Study subjects will receive sitravatinib capsule once daily and in combination with tislelizumab IV once every 3 weeks.

Experimental: Anti-PD-1/PD-L1 antibody refractory/resistant HCC Drug: Sitravatinib and tislelizumab
Study subjects will receive sitravatinib capsule once daily and in combination with tislelizumab IV once every 3 weeks.

Experimental: Anti-PD-1/PD-L1 antibody naive G/GEJ cancer Drug: Sitravatinib and tislelizumab
Study subjects will receive sitravatinib capsule once daily and in combination with tislelizumab IV once every 3 weeks.




Primary Outcome Measures :
  1. Phase 1: Number of participants with adverse events (AEs) and serious adverse events (SAEs) per NCI-CTCAE version 5.0 [ Time Frame: Up to approximately 3 years ]
  2. Phase 2: Objective response rate (ORR) [ Time Frame: Up to approximately 3 years ]
    ORR based on RECIST v1.1 by investigator



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologically or cytologically confirmed, unresectable, locally advanced, or metastatic HCC/GC/GEJC
  • Able to provide written informed consent and can understand and agree to comply with the requirements of the study and the schedule of assessments
  • Age ≥ 18 years on the day of signing the ICF (or the legal age of consent in the jurisdiction in which the study is taking place)
  • Adequate organ function
  • Females of childbearing potential must be willing to use a highly effective method of birth control for the duration of the study, and ≥ 120 days after the last dose of study drug(s), and have a negative serum pregnancy test ≤ 7 days of first dose of study drug(s)
  • Nonsterile males must be willing to use a highly effective method of birth control for the duration of the study and for ≥ 120 days after the last dose of study drug(s)
  • Failed current standard-of-care treatment, or standard-of-care treatment is considered not appropriate at present

Exclusion Criteria:

  • Active leptomeningeal disease or uncontrolled brain metastasis.
  • Active autoimmune diseases or history of autoimmune diseases that may relapse
  • Any active malignancy ≤ 2 years
  • History of interstitial lung disease, noninfectious pneumonitis or uncontrolled diseases including pulmonary fibrosis, acute lung diseases, etc
  • Severe chronic or active infections (including tuberculosis infection, etc) requiring systemic antibacterial, antifungal, or antiviral therapy within 14 days prior to first dose of study drug(s).
  • Known history of human immunodeficiency virus (HIV) infection
  • Untreated chronic hepatitis B or chronic hepatitis B virus (HBV) carriers.
  • Any major surgical procedure requiring general anesthesia ≤ 28 days before the first dose of study drug(s)
  • Prior allogeneic stem cell transplantation or organ transplantation
  • Inadequately controlled hypertension (defined as systolic blood pressure > 150 mmHg and/or diastolic blood pressure > 100 mmHg)
  • Bleeding or thrombotic disorders or use of anticoagulants such as warfarin or similar agents requiring therapeutic INR monitoring
  • Any systemic chemotherapy within 28 days of the first dose of study drug(s) or hormone therapy, targeted therapy, or any investigational therapies Toxicities (as a result of prior anticancer therapy) that have not recovered to baseline or stabilized, except for AEs not considered a likely safety risk (eg, alopecia, neuropathy, and specific laboratory abnormalities)
  • Inability to swallow capsules or disease significantly affecting gastrointestinal function
  • Pregnant or breastfeeding woman"

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03941873


Contacts
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Contact: BeiGene +1-877-828-5568 clinicaltrials@beigene.com

Locations
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China, Anhui
The Second Hospital of Anhui Medical University Not yet recruiting
Hefei, Anhui, China, 230000
China, Beijing
Beijing Cancer Hospital Not yet recruiting
Beijing, Beijing, China, 100142
Contact: Chunyi Hao         
Peking Union Medical College Hospital Not yet recruiting
Beijing, Beijing, China, 100730
Contact: Haitao Zhao         
China, Fujian
Fujian Medical university union hospital Not yet recruiting
Fuzhou, Fujian, China, 350001
Contact: Xiaoyan Lin         
Fujian Cancer Hospital Not yet recruiting
Fuzhou, Fujian, China, 350014
Contact: Hailan Lin         
China, Guangdong
Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University Not yet recruiting
Guangzhou, Guangdong, China, 510120
Contact: Yajin Chen         
Nanfang Hospital Not yet recruiting
Guangzhou, Guangdong, China, 510515
Contact: Yabing Guo         
China, Heilongjiang
Harbin Medical University Cancer Hospital Recruiting
Harbin, Heilongjiang, China, 150000
China, Henan
Henan Cancer Hospital Not yet recruiting
Zhenzhou, Henan, China, 450008
Contact: Jufeng Wang         
China, Hubei
Union Hospital Tongji Medical College Huazhong University of Science and Technology Not yet recruiting
Wuhan, Hubei, China, 430000
Hubei cancer hospital Not yet recruiting
Wuhan, Hubei, China, 430070
Contact: Feng Zhang         
Zhongnan Hospital of Wuhan University Recruiting
Wuhan, Hubei, China, 430071
Contact: Fuxiang Zhou         
China, Jiangsu
The 81st Hospital of Chinese PLA Recruiting
Nanjing, Jiangsu, China, 210000
China, Jiangxi
The First affiliated hospital of Nanchang University Not yet recruiting
Nanchang, Jiangxi, China, 330006
Contact: Jianping Xiong         
China, Liaoning
The First Hospital of China Medical University Not yet recruiting
Shenyang, Liaoning, China, 110000
Liaoning Cancer Hospital & Institute Not yet recruiting
Shenyang, Liaoning, China, 110042
Contact: Jingdong Zhang         
China, Shanghai
Zhongshan Hospital Fudan University Not yet recruiting
Shanghai, Shanghai, China, 200000
Fudan University Shanghai Cancer Center Not yet recruiting
Shanghai, Shanghai, China, 200120
Shanghai East Hospital Recruiting
Shanghai, Shanghai, China, 200120
China, Zhejiang
Sir Run Run Shaw Hospital Zhejiang University School of Medicine Not yet recruiting
Hangzhou, Zhejiang, China, 310000
The First Affiliated Hospital Zhejiang University Not yet recruiting
Hangzhou, Zhejiang, China, 310000
Zhejiang Cancer Hospital Recruiting
Hangzhou, Zhejiang, China, 310000
Sponsors and Collaborators
BeiGene
Investigators
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Principal Investigator: Jin Li, PhD Shanghai East Hospital
Principal Investigator: Shukui Qin, MD The 81st hospital of Chinese PLA

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Responsible Party: BeiGene
ClinicalTrials.gov Identifier: NCT03941873     History of Changes
Other Study ID Numbers: BGB-900-104
CTR20182149 ( Registry Identifier: Center for drug evaluation, CFDA )
First Posted: May 8, 2019    Key Record Dates
Last Update Posted: November 18, 2019
Last Verified: November 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by BeiGene:
Carcinoma
HCC
G/GEJ Cancer
Additional relevant MeSH terms:
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Carcinoma, Hepatocellular
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Liver Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Liver Diseases
Antibodies
Immunologic Factors
Physiological Effects of Drugs