A Study to Evaluate Rivoceranib Plus Best Supportive Care Compared to Placebo Plus Best Supportive Care in Participants With Gastric Cancer
- Conditions
- Gastric CancerGastric Adenocarcinoma
- Interventions
- Drug: Placebo
- Registration Number
- NCT03042611
- Lead Sponsor
- Elevar Therapeutics
- Brief Summary
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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 460
-
Documented primary diagnosis of histologic- or cytologic-confirmed adenocarcinoma of the stomach or gastroesophageal junction.
-
Locally advanced unresectable or metastatic disease that has progressed since last treatment.
-
One or more measurable or nonmeasurable evaluable lesions per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1).
-
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
-
Disease progression within 6 months after the last treatment.
-
Adequate bone-marrow, renal and liver function.
-
Eastern Cooperative Oncology Group (ECOG) performance status of ≤1.
-
Expected survival of ≥12 weeks, in the opinion of the investigator.
- 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.
- 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.
- 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.).
- 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.
- 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.
- Previous treatment with rivoceranib.
- Known hypersensitivity to rivoceranib or components of the formulation.
- Concomitant treatment with strong inhibitors or inducers of CYP3A4, CYP2C9, and CYP2C19.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo 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. Rivoceranib Plus BSC Rivoceranib 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.
- Primary Outcome Measures
Name Time Method Overall Survival (OS) 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.
- Secondary Outcome Measures
Name Time Method Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) 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.
Objective Response Rate (ORR) Per RECIST 1.1 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.
Disease Control Rate (DCR) 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.
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) 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.
Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Stomach Cancer Specific (EORTC QLQ-STO22) Score 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.
Change From Baseline in EuroQol 5-Dimension 5-Level Visual Analogue Scale (EQ-5D-5L VAS) Score 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.
Number of Participants Per QOL Dimension Response as Measured by the EuroQol 5-Dimension 5-Level (EQ-5D-5L) Questionnaire 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.
Trial Locations
- Locations (95)
Ospedali Riuniti di Ancona - SOD Clinica Oncologica
🇮🇹Torrette, Italy
U.O Di Oncologia Ospedale Degli Infermi
🇮🇹Faenza, Italy
Chungbuk National University Hospital
🇰🇷Chungbuk, Korea, Republic of
Ogarev Mordovia State University
🇷🇺Saransk, Russian Federation
Communal Institution "Vinnytsia Regional Clinical Oncology Dispensary"
🇺🇦Vinnytsia, Ukraine
Kherson Regional Oncological Dispensary
🇺🇦Kherson, Ukraine
Municipal Institution "Kyiv City Clinical Oncological Center"
🇺🇦Kyiv, Ukraine
Kaohsiung Medical University Hospital
🇨🇳Kaohsiung, Sanmin Dist, Taiwan
National CHeng Kung University Hospital
🇨🇳Tainan, Tainan City, Taiwan
Osaka University Hospital
🇯🇵Osaka, Suita, Japan
Ospedale "Felice Lotti"
🇮🇹Pontedera, Italy
Inje University Haeundae Paik Hospital
🇰🇷Busan, Korea, Republic of
Pusan National University Hospital
🇰🇷Busan, Korea, Republic of
Mayo Clinic Phoenix
🇺🇸Scottsdale, Arizona, United States
Highlands Oncology Group
🇺🇸Rogers, Arkansas, United States
Mayo Clinic Cancer Center
🇺🇸Rochester, Minnesota, United States
Hudson Valley Cancer Centre
🇺🇸Hawthorne, New York, United States
Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Centre Hospitalier Franco-Britannique; Oncologie Médicale
🇫🇷Levallois-Perret, France
Institut Gustave Roussy
🇫🇷Villejuif, France
Centre Leon-Berard (CLB)
🇫🇷Lyon, France
Institut Regional du Cancer Montpellier (ICM)
🇫🇷Montpellier, France
Centre Antoine-Lacassagne
🇫🇷Nice, France
Charite - Universitaetsmedizin Berlin - Medizinische Klinik mit Schwerpunkt Haematologie, Onkologie und Tumorimmunologie
🇩🇪Berlin, Germany
Facharztzentrum Eppendorf - Haematologisch-Onkologische Praxis Eppendorf (HOPE)
🇩🇪Hamburg, Germany
Universitätsklinik Marburg, Klinik fur Innere Medizin, Schwerpunkt Haematologie, Onkologie und Immunologie
🇩🇪Marburg, Germany
"Institut für Klinisch-Onkologische Forschung (IKF) Krankenhaus Nordwest gGmbH UCT - Universitäres Centrum für Tumorerkrankungen Frankfurt
🇩🇪Frankfurt, Germany
Rimini Hospital
🇮🇹Rimini, Italy
Magna Graecia University- Department of Experimental and Clinical Medicine
🇮🇹Catanzaro, Italy
Fondazione IRCCS-Istituto Nazionale Tumori
🇮🇹Milano, Italy
Policlinico di Modena-Azienda Ospedaliero Universitaria di Modena.Oncologia ed Ematologia.
🇮🇹Modena, Italy
Veneto Oncology Institute (IOV-IRCCS), Melanoma & Esophageal Oncology Unit
🇮🇹Padova, Italy
Ospedale di Piacenza - Oncology and heamatology
🇮🇹Piacenza, Italy
IRCCS/Arcispedale Santa Maria Nuova
🇮🇹Reggio Emilia, Italy
National Cancer Center Hospital
🇯🇵Tokyo, Chuo-ku, Japan
Hyogo Cancer Center
🇯🇵Hyogo, Akasi-city, Japan
Chiba Cancer Center
🇯🇵Chiba, Chiba City, Japan
National Cancer Center Hospital East
🇯🇵Chiba, Kashiwa, Japan
Japan Community Health Care Organization Kyushu Hospital
🇯🇵Fukuoka, Kitakyushu-shi, Japan
The Cancer Institute Hospital of Japanese Foundation For Cancer Research
🇯🇵Tokyo, Koto-ku, Japan
Kyushu University Hospital
🇯🇵Fukuoka, Higashi-ku, Japan
National Hospital Organization Shikoku Cancer Center
🇯🇵Ehime, Matsuyama, Japan
Saku Central Hospital Advanced Care Center
🇯🇵Nagano, Saku-shi, Japan
Saitama Cancer Center
🇯🇵Saitama, Kitaadachi-gun, Japan
St. Marianna University School of Medicine Hospital
🇯🇵Kanagawa, Kawasaki-shi, Japan
Hokkaido University Hospital
🇯🇵Hokkaido, Sapporo, Japan
Hallym University Sacred Heart Hospital
🇰🇷Anyang-si, Gyeonggi-do, Korea, Republic of
Aichi Cancer Center Hospital
🇯🇵Nagoya, Japan
Keio University Hospital
🇯🇵Tokyo, Shinjuku-ku, Japan
Ajou University Hospital
🇰🇷Suwon-si, Gyonggi-do, Korea, Republic of
National Cancer Center
🇰🇷Goyang-si, Gyeonggi-do, Korea, Republic of
Dong-A University Hospital
🇰🇷Busan, Korea, Republic of
Chungbuk National University Medical Center
🇰🇷Chuncheon, Korea, Republic of
Keimyung University Dongsan Medical Center
🇰🇷Daegu, Korea, Republic of
Yeungnam University Medical Center
🇰🇷Daegu, Korea, Republic of
Kyungpook National University Medical Center
🇰🇷Daegu, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷Gyeonggi-do, Korea, Republic of
Chungnam National University Hospital
🇰🇷Daejeon, Korea, Republic of
Korea University Anam Hospital
🇰🇷Seoul, Korea, Republic of
Severence Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Veterans Health Service (VHS) Medical Center
🇰🇷Seoul, Korea, Republic of
Gachon University Gil Medical Center
🇰🇷Incheon, Korea, Republic of
ASAN Medical Center
🇰🇷Seoul, Korea, Republic of
Gangnam Severance Hospital
🇰🇷Seoul, Korea, Republic of
Korea University Guro Hospital
🇰🇷Seoul, Korea, Republic of
Ulsan University Hospital
🇰🇷Ulsan, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Szpital Uniwersytecki w Krakowie, Odział Kliniczny Onkologii
🇵🇱Kraków, Poland
Saint Constantin Hospital (TEO HEALTH SA)
🇷🇴Brasov, Romania
Centrul de Oncologie "Sf. Nectarie", Sectia de Oncologie Medicala
🇷🇴Craiova, Romania
Institutul Oncologic "Prof. Dr. Ion Chiricuta" Cluj-Napoca, Sectia de Radioterapie I
🇷🇴Cluj-Napoca, Romania
S.C. Medisprof S.R.L.
🇷🇴Cluj-Napoca, Romania
State Budgetary Healthcare Institution of Arkhangelsk Region "Arkhangelsk Clinical Oncology Dispensary"
🇷🇺Arkhangelsk, Russian Federation
State Healthcare Institution "Kursk Regional Clinical Oncology Dispensary"
🇷🇺Kursk, Russian Federation
Omsk regional clinical oncology center
🇷🇺Omsk, Russian Federation
Budgetary Healthcare Institution of Orel Region "Orel Oncology Dispensary"
🇷🇺Oryol, Russian Federation
Taipei Veterans General Hospital
🇨🇳Taipei, Beitou Dist, Taiwan
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
🇷🇺St. Petersburg, Russian Federation
Chi Mei Medical Center - LiouYing Branch
🇨🇳Tainan, Liuying DIst, Taiwan
Chang Gung Memorial Hospital - Linko Branch
🇨🇳Taoyuan, Kuei Shan Hsiang, Taiwan
Chang Gung Memorial Hospital - Kaohsiung Branch
🇨🇳Kaohsiung, Niaosong Dist, Taiwan
China Medical University Hospital
🇨🇳Taichung, Taichung City, Taiwan
National Taiwan University Hospital
🇨🇳Taipei, Zhongzheng Dist, Taiwan
Dnipropetrovsk Medical Academy, Department of Oncology
🇺🇦Dnipro, Ukraine
Royal Marsden Hospital Surrey
🇬🇧Sutton, United Kingdom
Communal Institution "Ivano-Frankivsk Regional Oncological Center"
🇺🇦Ivano-Frankivsk, Ukraine
Communal Institution "Kharkiv Regional Clinical Oncology Center ", Chemotherapy department #1, Medical Academy of Postgraduate Education, Oncology and Pediatric Oncology
🇺🇦Kharkiv, Ukraine
State Budgetary Healthcare Institution of Stavropol Territory "Pyatigorsk Oncology Dispensary"
🇷🇺Pyatigorsk, Russian Federation
State Budgetary Healthcare Institution "Republican Clinical Oncology Dispensary"
🇷🇺Ufa, Russian Federation
Communal Institution "Transcarpathian Regional Clinical Oncological Center"
🇺🇦Uzhhorod, Ukraine
Royal Marsden Hospital London
🇬🇧London, United Kingdom
The Christie NHS Foundation Trust
🇬🇧Manchester, United Kingdom
Centrum Onkologii-Instytut im. Marii Skłodowskiej-Curie, Klinika Gastroenterologii Onkologicznej
🇵🇱Warszawa, Poland
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
🇺🇦Zaporizhzhia, Ukraine
Municipal Institution Kryvyi Rig Oncology Dispensary", Chemotherapy Department
🇺🇦Kryvyi Rih, Ukraine