A Study to Evaluate Rivoceranib Plus Best Supportive Care Compared to Placebo Plus Best Supportive Care in Participants With Gastric Cancer (ANGEL)

June 15, 2022 updated by: Elevar Therapeutics

A Prospective, Randomized, Double-Blinded, Placebo-Controlled, Multinational, Multicenter, Parallel-group, Phase III Study to Evaluate the Efficacy and Safety of Apatinib Plus Best Supportive Care (BSC) Compared to Placebo Plus BSC in Patients With Advanced or Metastatic Gastric Cancer

The purpose of this study is to evaluate the efficacy and safety of rivoceranib plus best supportive care (BSC) compared to placebo plus BSC in participants with advanced or metastatic gastric cancer (GC).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

460

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Levallois-Perret, France, 92300
        • Centre Hospitalier Franco-Britannique; Oncologie Médicale
      • Lyon, France, 69008
        • Centre Leon-Berard (CLB)
      • Montpellier, France, 34298
        • Institut régional du Cancer Montpellier (ICM)
      • Nice, France, 06189
        • Centre Antoine-Lacassagne
      • Villejuif, France, 94805
        • Institut Gustave Roussy
  • Germany
      • Berlin, Germany, 13353
        • Charite - Universitaetsmedizin Berlin - Medizinische Klinik mit Schwerpunkt Haematologie, Onkologie und Tumorimmunologie
      • Frankfurt, Germany, 60488
        • "Institut für Klinisch-Onkologische Forschung (IKF) Krankenhaus Nordwest gGmbH UCT - Universitäres Centrum für Tumorerkrankungen Frankfurt
      • Hamburg, Germany, 20249
        • Facharztzentrum Eppendorf - Haematologisch-Onkologische Praxis Eppendorf (HOPE)
      • Marburg, Germany, 35043
        • Universitätsklinik Marburg, Klinik fur Innere Medizin, Schwerpunkt Haematologie, Onkologie und Immunologie
  • Italy
      • Catanzaro, Italy, 88100
        • Magna Graecia University- Department of Experimental and Clinical Medicine
      • Faenza, Italy, 48018
        • U.O Di Oncologia Ospedale Degli Infermi
      • Milano, Italy, 20133
        • Fondazione IRCCS-Istituto Nazionale Tumori
      • Modena, Italy, 41124
        • Policlinico di Modena-Azienda Ospedaliero Universitaria di Modena.Oncologia ed Ematologia.
      • Padova, Italy, 35128
        • Veneto Oncology Institute (IOV-IRCCS), Melanoma & Esophageal Oncology Unit
      • Piacenza, Italy, 29121
        • Ospedale di Piacenza - Oncology and heamatology
      • Pontedera, Italy, 56025
        • Ospedale "Felice Lotti"
      • Reggio Emilia, Italy, 42123
        • IRCCS/Arcispedale Santa Maria Nuova
      • Rimini, Italy, 47923
        • Rimini Hospital
      • Torrette, Italy, 60126
        • Ospedali Riuniti di Ancona - SOD Clinica Oncologica
  • Japan
      • Nagoya, Japan, 464-8681
        • Aichi Cancer Center Hospital
    • Akasi-city
      • Hyogo, Akasi-city, Japan, 673-0021
        • Hyogo Cancer Center
    • Chiba City
      • Chiba, Chiba City, Japan, 260-8717
        • Chiba cancer center
    • Chuo-ku
      • Tokyo, Chuo-ku, Japan, 104-0045
        • National Cancer Center Hospital
    • Higashi-ku
      • Fukuoka, Higashi-ku, Japan, 812-8582
        • Kyushu University Hospital
    • Kashiwa
      • Chiba, Kashiwa, Japan, 277-8577
        • National Cancer Center Hospital East
    • Kawasaki-shi
      • Kanagawa, Kawasaki-shi, Japan, 216-8511
        • St. Marianna University School of Medicine Hospital
    • Kitaadachi-gun
      • Saitama, Kitaadachi-gun, Japan, 362-0806
        • Saitama Cancer Center
    • Kitakyushu-shi
      • Fukuoka, Kitakyushu-shi, Japan, 806-8501
        • Japan Community Health care Organization Kyushu Hospital
    • Koto-ku
      • Tokyo, Koto-ku, Japan, 135-8550
        • The Cancer Institute Hospital of Japanese Foundation For Cancer Research
    • Matsuyama
      • Ehime, Matsuyama, Japan, 791-0280
        • National Hospital Organization Shikoku Cancer Center
    • Saku-shi
      • Nagano, Saku-shi, Japan, 385-0051
        • Saku Central Hospital Advanced Care Center
    • Sapporo
      • Hokkaido, Sapporo, Japan, 060-8648
        • Hokkaido University Hospital
    • Shinjuku-ku
      • Tokyo, Shinjuku-ku, Japan, 160-8582
        • Keio University Hospital
    • Suita
      • Osaka, Suita, Japan, 565-0871
        • Osaka University Hospital
  • Korea, Republic of
      • Busan, Korea, Republic of, 49241
        • Pusan National University Hospital
      • Busan, Korea, Republic of, 48108
        • Inje University Haeundae Paik Hospital
      • Busan, Korea, Republic of, 49201
        • Dong-A University Hospital
      • Chuncheon, Korea, Republic of, 41404
        • Chungbuk National University Medical Center
      • Chungbuk, Korea, Republic of, 54907
        • Chungbuk National University Hospital
      • Daegu, Korea, Republic of, 41404
        • Kyungpook National University Medical Center
      • Daegu, Korea, Republic of, 42415
        • Yeungnam University Medical Center
      • Daegu, Korea, Republic of, 41931
        • Keimyung University Dongsan Medical Center
      • Daejeon, Korea, Republic of, 35015
        • Chungnam National University Hospital
      • Gyeonggi-do, Korea, Republic of, 13620
        • Seoul National University Bundang Hospital
      • Incheon, Korea, Republic of, 21555
        • Gachon University Gil Medical Center
      • Seoul, Korea, Republic of, 05505
        • Asan Medical Center
      • Seoul, Korea, Republic of, 02841
        • Korea University Anam Hospital
      • Seoul, Korea, Republic of, 08308
        • Korea University Guro Hospital
      • Seoul, Korea, Republic of, 06351
        • Samsung Medical Center
      • Seoul, Korea, Republic of, 06273
        • Gangnam Severance Hospital
      • Seoul, Korea, Republic of, 03722
        • Severence Hospital, Yonsei University Health System
      • Seoul, Korea, Republic of, 05368
        • Veterans Health Service (VHS) Medical Center
      • Ulsan, Korea, Republic of, 44033
        • Ulsan University Hospital
    • Gyeonggi-do
      • Anyang-si, Gyeonggi-do, Korea, Republic of, 14069
        • Hallym University Sacred Heart Hospital
      • Goyang-si, Gyeonggi-do, Korea, Republic of, 10408
        • National Cancer Center
    • Gyonggi-do
      • Suwon-si, Gyonggi-do, Korea, Republic of, 16499
        • Ajou University Hospital
  • Poland
      • Kraków, Poland, 31-501
        • Szpital Uniwersytecki w Krakowie, Odział Kliniczny Onkologii
      • Warszawa, Poland, 02-781
        • Centrum Onkologii-Instytut im. Marii Skłodowskiej-Curie, Klinika Gastroenterologii Onkologicznej
  • Romania
      • Brasov, Romania, 500091
        • Saint Constantin Hospital (TEO HEALTH SA)
      • Cluj-Napoca, Romania, 400015
        • Institutul Oncologic "Prof. Dr. Ion Chiricuta" Cluj-Napoca, Sectia de Radioterapie I
      • Cluj-Napoca, Romania, 400058
        • S.C. Medisprof S.R.L.
      • Craiova, Romania, 200347
        • Centrul de Oncologie "Sf. Nectarie", Sectia de Oncologie Medicala
  • Russian Federation
      • Arkhangelsk, Russian Federation, 163045
        • State Budgetary Healthcare Institution of Arkhangelsk Region "Arkhangelsk Clinical Oncology Dispensary"
      • Kursk, Russian Federation, 305035
        • State Healthcare Institution "Kursk Regional Clinical Oncology Dispensary"
      • Omsk, Russian Federation, 644013
        • Omsk Regional Clinical Oncology Center
      • Oryol, Russian Federation, 302020
        • Budgetary Healthcare Institution of Orel Region "Orel Oncology Dispensary"
      • Pyatigorsk, Russian Federation, 357502
        • State Budgetary Healthcare Institution of Stavropol Territory "Pyatigorsk Oncology Dispensary"
      • Saransk, Russian Federation, 430032
        • Ogarev Mordovia State University
      • St. Petersburg, Russian Federation, 197022
        • Federal State Budgetary Educational Institution of Higher Education "Academician I.P. Pavlov First St. Petersburg State Medical University" of the Ministry of Heaithcare of the Russian Federation
      • Ufa, Russian Federation, 450054
        • State Budgetary Healthcare Institution "Republican Clinical Oncology Dispensary"
  • Taiwan
    • Beitou Dist
      • Taipei, Beitou Dist, Taiwan, 11217
        • Taipei Veterans General Hospital
    • Kuei Shan Hsiang
      • Taoyuan, Kuei Shan Hsiang, Taiwan, 333
        • Chang Gung Memorial Hospital - Linko Branch
    • Liuying DIst
      • Tainan, Liuying DIst, Taiwan, 736
        • Chi Mei Medical Center - Liouying Branch
    • Niaosong Dist
      • Kaohsiung, Niaosong Dist, Taiwan, 83301
        • Chang Gung Memorial Hospital - Kaohsiung Branch
    • Sanmin Dist
      • Kaohsiung, Sanmin Dist, Taiwan, 80708
        • Kaohsiung Medical University Hospital
    • Taichung City
      • Taichung, Taichung City, Taiwan, 40447
        • China Medical University Hospital
    • Tainan City
      • Tainan, Tainan City, Taiwan, 70403
        • National Cheng Kung University Hospital
    • Zhongzheng Dist
      • Taipei, Zhongzheng Dist, Taiwan, 100
        • National Taiwan University Hospital
  • Ukraine
      • Dnipro, Ukraine, 49102
        • Dnipropetrovsk Medical Academy, Department of Oncology
      • Ivano-Frankivsk, Ukraine, 76000
        • Communal Institution "Ivano-Frankivsk Regional Oncological Center"
      • Kharkiv, Ukraine, 61070
        • Communal Institution "Kharkiv Regional Clinical Oncology Center ", Chemotherapy department #1, Medical Academy of Postgraduate Education, Oncology and Pediatric Oncology
      • Kherson, Ukraine, 73035
        • Kherson Regional Oncological Dispensary
      • Kryvyi Rih, Ukraine, 50048
        • Municipal Institution Kryvyi Rig Oncology Dispensary", Chemotherapy Department
      • Kyiv, Ukraine, 03115
        • Municipal Institution "Kyiv City Clinical Oncological Center"
      • Uzhhorod, Ukraine, 88014
        • Communal Institution "Transcarpathian Regional Clinical Oncological Center"
      • Vinnytsia, Ukraine, 21029
        • Communal Institution "Vinnytsia Regional Clinical Oncology Dispensary"
      • Zaporizhzhia, Ukraine, 69040
        • State institution "Zaporizhzhia Medical Academy of Postgraduate Education MOH Ukraine", Department of oncology based on Municipal Institution "Zaporizhzhia Regional Clinical Oncology Dispensary" Zaporizhzhia Regional Assembly
  • United Kingdom
      • London, United Kingdom, SW3 6JJ
        • Royal Marsden Hospital London
      • Manchester, United Kingdom, M20 4BX
        • The Christie NHS Foundation Trust
      • Sutton, United Kingdom, SM2 5PT
        • Royal Marsden Hospital Surrey
  • United States
    • Arizona
      • Scottsdale, Arizona, United States, 85259
        • Mayo Clinic Phoenix
    • Arkansas
      • Rogers, Arkansas, United States, 72758
        • Highlands Oncology Group
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Karmanos Cancer Institute
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic Cancer Center
    • New York
      • Hawthorne, New York, United States, 10532
        • Hudson Valley Cancer Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Documented primary diagnosis of histologic- or cytologic-confirmed adenocarcinoma of the stomach or gastroesophageal junction.
  2. Locally advanced unresectable or metastatic disease that has progressed since last treatment.
  3. One or more measurable or nonmeasurable evaluable lesions per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1).

  4. Failure or intolerance to at least 2 prior lines of standard chemotherapies with each containing one or more of the following agents:

    • fluoropyrimidine (intravenous [IV] 5-fluorouracil [5-FU] capecitabine, or S-1),
    • platinum (cisplatin or oxaliplatin),
    • taxanes (paclitaxel or docetaxel) or epirubicin,
    • irinotecan,
    • trastuzumab in case of human epidermal growth factor receptor 2 (HER2)-positive,
    • ramucirumab
    • nivolumab
    • pembrolizumab
  5. Disease progression within 6 months after the last treatment.
  6. Adequate bone-marrow, renal and liver function.
  7. Eastern Cooperative Oncology Group (ECOG) performance status of ≤1.
  8. Expected survival of ≥12 weeks, in the opinion of the investigator.

Exclusion Criteria:

  1. History of another malignancy within 2 years prior to randomization except for the following: Bladder tumors considered superficial such as noninvasive (T1a) and carcinoma in situ (CIS); Curatively treated cervical CIS; Thyroid papillary cancer with prior treatment; Carcinoma of the skin without melanomatous features; Prostate cancer which had been surgically or medically treated and not likely to recur within 2 years.
  2. Central nervous system (CNS) metastases as shown by radiology records or clinical evidence of symptomatic CNS involvement in the last 3 months prior to randomization.
  3. Cytotoxic chemotherapy, surgery, immunotherapy, radiotherapy or other targeted therapies within 3 weeks (4 weeks in cases of ramucirumab, mitomycin C, nitrosourea, lomustine; 1 week in case of biopsy) prior to randomization (Adjuvant radiotherapy given to local area for non-curative symptom relief is allowed until 2 weeks before randomization.).
  4. Therapy with clinically significant systemic anticoagulant or antithrombotic agents within 7 days prior to randomization that may prevent blood clotting and, in the investigator's opinion, could place the participant at risk.
  5. Participants who had therapeutic paracentesis of ascites (>1 Liter [L]) within the 3 months prior to starting study treatment or who, in the opinion of the investigator, will likely need therapeutic paracentesis of ascites (>1L) within 3 months of starting study treatment.
  6. Previous treatment with rivoceranib.
  7. Known hypersensitivity to rivoceranib or components of the formulation.
  8. Concomitant treatment with strong inhibitors or inducers of CYP3A4, CYP2C9, and CYP2C19.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: TRIPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Rivoceranib Plus BSC
Participants will receive rivoceranib 700 milligrams (mg) orally once per day during each cycle plus BSC. BSC is defined as palliative, non-cancer therapy. Each cycle duration is 28 days.
Drug: Rivoceranib
Oral tablet
Other Names:
  • Apatinib
EXPERIMENTAL: Placebo
Participants will receive matching placebo to rivoceranib orally once per day during each cycle plus BSC. BSC is defined as palliative, non-cancer therapy. Each cycle duration is 28 days.
Drug: Placebo
Oral tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival (OS)
Time Frame: Day 1 (randomization) up to approximately 36 months
OS was defined as the time from randomization to death. Participants alive or lost to follow-up at the end of study (EOS) were censored.
Day 1 (randomization) up to approximately 36 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Time Frame: Up to approximately 24 months
PFS was defined as the time from randomization to either documented radiological progression or death from any cause. Participants alive and free of progression at the EOS were censored.
Up to approximately 24 months
Objective Response Rate (ORR) Per RECIST 1.1
Time Frame: Up to approximately 24 months
ORR was defined as the percentage of participants in the analysis population with the best overall response of Complete Response (CR: disappearance of all target lesions and reduction in short axis of any nodal target lesions to <10 millimeter [mm]) or a Partial Response (PR: ≥30% decrease in the sum of the longest diameters of the target lesions, taking as a reference the baseline sum diameters) per RECIST 1.1.
Up to approximately 24 months
Disease Control Rate (DCR)
Time Frame: Up to approximately 24 months
DCR was defined as the proportion of participants with a Best Overall Response of CR, PR, or stable disease (SD: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as a reference the smallest sum diameter while on study) per RECIST 1.1.
Up to approximately 24 months
Change From Baseline in Global Health Status/Quality of Life (QoL) Measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)
Time Frame: Baseline, End of Treatment (EOT) (Up to 24 months)
EORTC QLQ-C30 is a cancer specific Questionnaire with 30 questions for assessing the health-related QOL of cancer participants. The questionnaire incorporates 5 functional scales, 4 symptom scales, a global QOL scale, and single items for the assessment of additional systems commonly reported by cancer participants. All items are scored on 4-point Likert scales, ranging from 1 ('not at all') to 4 ('very much'), with the exception of 2 items in the global QOL scale which use modified 7-point linear analog scales. A linear transformation was used to standardize all scores and single-items to a scale of 0 to 100. For the functioning scales, a higher score indicated greater functioning and for the symptom scales, a higher score indicated a greater symptom burden.
Baseline, End of Treatment (EOT) (Up to 24 months)
Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Stomach Cancer Specific (EORTC QLQ-STO22) Score
Time Frame: Baseline, EOT (Up to 24 months)
EORTC QLQ-STO22 is a 22-item gastric cancer-specific questionnaire-integrating system for assessing the health-related QOL of gastric cancer participants. Most questions use 4-point scale (1 'Not at all' to 4 'Very much'; 1 question was a yes or no answer). A linear transformation was used to standardize all scores and single-items to a scale of 0 to 100. For the functioning scales, a higher score indicates greater functioning and for the symptom scales, a higher score indicates a greater symptom burden.
Baseline, EOT (Up to 24 months)
Change From Baseline in EuroQol 5-Dimension 5-Level Visual Analogue Scale (EQ-5D-5L VAS) Score
Time Frame: Baseline, EOT (Up to 24 months)
EQ-5D-5L Questionnaire consists of EQ-5D-5L descriptive system and the visual analogue scale (VAS). The descriptive system comprises the 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and each dimension has 5 levels. The VAS is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state.
Baseline, EOT (Up to 24 months)
Number of Participants Per QOL Dimension Response as Measured by the EuroQol 5-Dimension 5-Level (EQ-5D-5L) Questionnaire
Time Frame: EOT (Month 24)
EQ-5D-5L Questionnaire comprises the 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and each dimension has 5 levels of response.
EOT (Month 24)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Elevar Therapeutics

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

March 14, 2017

Primary Completion (ACTUAL)

February 15, 2019

Study Completion (ACTUAL)

September 23, 2020

Study Registration Dates

First Submitted

January 24, 2017

First Submitted That Met QC Criteria

February 2, 2017

First Posted (ESTIMATE)

February 3, 2017

Study Record Updates

Last Update Posted (ACTUAL)

July 8, 2022

Last Update Submitted That Met QC Criteria

June 15, 2022

Last Verified

June 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LSK-AM301

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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