Clinical trial NCT03042611: A Study to Evaluate Rivoceranib Plus Best Supportive Care Compared to Placebo Plus Best Supportive Care in Participants With Gastric Cancer
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Gastric Cancer
Gastric Adenocarcinoma
Keywords: Gastric Cancer
Gastric Adenocarcinoma
Gastro-esophageal Cancer
Gastro-esophageal Junction Cancer
Stomach Cancer
Tumor
Oncology
Antiangiogenesis
Metastatic
Lead sponsor: Elevar Therapeutics
Sponsor class: INDUSTRY
First posted: 2017-02-03
Enrollment: 460
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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.

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: Day 1 (randomization) up to approximately 36 months
Secondary outcomes:
measure: Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
timeFrame: Up to approximately 24 months
measure: Objective Response Rate (ORR) Per RECIST 1.1
timeFrame: Up to approximately 24 months
measure: Disease Control Rate (DCR)
timeFrame: Up to approximately 24 months
measure: 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)
timeFrame: Baseline, End of Treatment (EOT) (Up to 24 months)
measure: Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Stomach Cancer Specific (EORTC QLQ-STO22) Score
timeFrame: Baseline, EOT (Up to 24 months)
measure: Change From Baseline in EuroQol 5-Dimension 5-Level Visual Analogue Scale (EQ-5D-5L VAS) Score
timeFrame: Baseline, EOT (Up to 24 months)
measure: Number of Participants Per QOL Dimension Response as Measured by the EuroQol 5-Dimension 5-Level (EQ-5D-5L) Questionnaire
timeFrame: EOT (Month 24)
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic Phoenix
state: Arizona
city: Rogers
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic Cancer Center
state: Minnesota
city: Hawthorne
country: United States
facility: Hudson Valley Cancer Centre
state: New York
city: Levallois-Perret
country: France
facility: Centre Hospitalier Franco-Britannique; Oncologie Médicale
city: Lyon
country: France
facility: Centre Leon-Berard (CLB)
city: Montpellier
country: France
facility: Institut Regional du Cancer Montpellier (ICM)
city: Nice
country: France
facility: Centre Antoine-Lacassagne
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Berlin
country: Germany
facility: Charite - Universitaetsmedizin Berlin - Medizinische Klinik mit Schwerpunkt Haematologie, Onkologie und Tumorimmunologie
city: Frankfurt
country: Germany
facility: "Institut für Klinisch-Onkologische Forschung (IKF) Krankenhaus Nordwest gGmbH UCT - Universitäres Centrum für Tumorerkrankungen Frankfurt
city: Hamburg
country: Germany
facility: Facharztzentrum Eppendorf - Haematologisch-Onkologische Praxis Eppendorf (HOPE)
city: Marburg
country: Germany
facility: Universitätsklinik Marburg, Klinik fur Innere Medizin, Schwerpunkt Haematologie, Onkologie und Immunologie
city: Catanzaro
country: Italy
facility: Magna Graecia University- Department of Experimental and Clinical Medicine
city: Faenza
country: Italy
facility: U.O Di Oncologia Ospedale Degli Infermi
city: Milano
country: Italy
facility: Fondazione IRCCS-Istituto Nazionale Tumori
city: Modena
country: Italy
facility: Policlinico di Modena-Azienda Ospedaliero Universitaria di Modena.Oncologia ed Ematologia.
city: Padova
country: Italy
facility: Veneto Oncology Institute (IOV-IRCCS), Melanoma & Esophageal Oncology Unit
city: Piacenza
country: Italy
facility: Ospedale di Piacenza - Oncology and heamatology
city: Pontedera
country: Italy
facility: Ospedale "Felice Lotti"
city: Reggio Emilia
country: Italy
facility: IRCCS/Arcispedale Santa Maria Nuova
city: Rimini
country: Italy
facility: Rimini Hospital
city: Torrette
country: Italy
facility: Ospedali Riuniti di Ancona - SOD Clinica Oncologica
city: Hyogo
country: Japan
facility: Hyogo Cancer Center
state: Akasi-city
city: Chiba
country: Japan
facility: Chiba Cancer Center
state: Chiba City
city: Tokyo
country: Japan
facility: National Cancer Center Hospital
state: Chuo-ku
city: Fukuoka
country: Japan
facility: Kyushu University Hospital
state: Higashi-ku
city: Chiba
country: Japan
facility: National Cancer Center Hospital East
state: Kashiwa
city: Kanagawa
country: Japan
facility: St. Marianna University School of Medicine Hospital
state: Kawasaki-shi
city: Saitama
country: Japan
facility: Saitama Cancer Center
state: Kitaadachi-gun
city: Fukuoka
country: Japan
facility: Japan Community Health Care Organization Kyushu Hospital
state: Kitakyushu-shi
city: Tokyo
country: Japan
facility: The Cancer Institute Hospital of Japanese Foundation For Cancer Research
state: Koto-ku
city: Ehime
country: Japan
facility: National Hospital Organization Shikoku Cancer Center
state: Matsuyama
city: Nagano
country: Japan
facility: Saku Central Hospital Advanced Care Center
state: Saku-shi
city: Hokkaido
country: Japan
facility: Hokkaido University Hospital
state: Sapporo
city: Tokyo
country: Japan
facility: Keio University Hospital
state: Shinjuku-ku
city: Osaka
country: Japan
facility: Osaka University Hospital
state: Suita
city: Nagoya
country: Japan
facility: Aichi Cancer Center Hospital
city: Anyang-si
country: Korea, Republic of
facility: Hallym University Sacred Heart Hospital
state: Gyeonggi-do
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
state: Gyeonggi-do
city: Suwon-si
country: Korea, Republic of
facility: Ajou University Hospital
state: Gyonggi-do
city: Busan
country: Korea, Republic of
facility: Inje University Haeundae Paik Hospital
city: Busan
country: Korea, Republic of
facility: Dong-A University Hospital
city: Busan
country: Korea, Republic of
facility: Pusan National University Hospital
city: Chuncheon
country: Korea, Republic of
facility: Chungbuk National University Medical Center
city: Chungbuk
country: Korea, Republic of
facility: Chungbuk National University Hospital
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Medical Center
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Medical Center
city: Daegu
country: Korea, Republic of
facility: Yeungnam University Medical Center
city: Daejeon
country: Korea, Republic of
facility: Chungnam National University Hospital
city: Gyeonggi-do
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Seoul
country: Korea, Republic of
facility: Korea University Anam Hospital
city: Seoul
country: Korea, Republic of
facility: Severence Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Veterans Health Service (VHS) Medical Center
city: Seoul
country: Korea, Republic of
facility: ASAN Medical Center
city: Seoul
country: Korea, Republic of
facility: Gangnam Severance Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
city: Ulsan
country: Korea, Republic of
facility: Ulsan University Hospital
city: Kraków
country: Poland
facility: Szpital Uniwersytecki w Krakowie, Odział Kliniczny Onkologii
city: Warszawa
country: Poland
facility: Centrum Onkologii-Instytut im. Marii Skłodowskiej-Curie, Klinika Gastroenterologii Onkologicznej
city: Brasov
country: Romania
facility: Saint Constantin Hospital (TEO HEALTH SA)
city: Cluj-Napoca
country: Romania
facility: Institutul Oncologic "Prof. Dr. Ion Chiricuta" Cluj-Napoca, Sectia de Radioterapie I
city: Cluj-Napoca
country: Romania
facility: S.C. Medisprof S.R.L.
city: Craiova
country: Romania
facility: Centrul de Oncologie "Sf. Nectarie", Sectia de Oncologie Medicala
city: Arkhangelsk
country: Russian Federation
facility: State Budgetary Healthcare Institution of Arkhangelsk Region "Arkhangelsk Clinical Oncology Dispensary"
city: Kursk
country: Russian Federation
facility: State Healthcare Institution "Kursk Regional Clinical Oncology Dispensary"
city: Omsk
country: Russian Federation
facility: Omsk regional clinical oncology center
city: Oryol
country: Russian Federation
facility: Budgetary Healthcare Institution of Orel Region "Orel Oncology Dispensary"
city: Pyatigorsk
country: Russian Federation
facility: State Budgetary Healthcare Institution of Stavropol Territory "Pyatigorsk Oncology Dispensary"
city: Saransk
country: Russian Federation
facility: Ogarev Mordovia State University
city: St. Petersburg
country: Russian Federation
facility: 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
city: Ufa
country: Russian Federation
facility: State Budgetary Healthcare Institution "Republican Clinical Oncology Dispensary"
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
state: Beitou Dist
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital - Linko Branch
state: Kuei Shan Hsiang
city: Tainan
country: Taiwan
facility: Chi Mei Medical Center - LiouYing Branch
state: Liuying DIst
city: Kaohsiung
country: Taiwan
facility: Chang Gung Memorial Hospital - Kaohsiung Branch
state: Niaosong Dist
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Hospital
state: Sanmin Dist
city: Taichung
country: Taiwan
facility: China Medical University Hospital
state: Taichung City
city: Tainan
country: Taiwan
facility: National CHeng Kung University Hospital
state: Tainan City
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
state: Zhongzheng Dist
city: Dnipro
country: Ukraine
facility: Dnipropetrovsk Medical Academy, Department of Oncology
city: Ivano-Frankivsk
country: Ukraine
facility: Communal Institution "Ivano-Frankivsk Regional Oncological Center"
city: Kharkiv
country: Ukraine
facility: Communal Institution "Kharkiv Regional Clinical Oncology Center ", Chemotherapy department #1, Medical Academy of Postgraduate Education, Oncology and Pediatric Oncology
city: Kherson
country: Ukraine
facility: Kherson Regional Oncological Dispensary
city: Kryvyi Rih
country: Ukraine
facility: Municipal Institution Kryvyi Rig Oncology Dispensary", Chemotherapy Department
city: Kyiv
country: Ukraine
facility: Municipal Institution "Kyiv City Clinical Oncological Center"
city: Uzhhorod
country: Ukraine
facility: Communal Institution "Transcarpathian Regional Clinical Oncological Center"
city: Vinnytsia
country: Ukraine
facility: Communal Institution "Vinnytsia Regional Clinical Oncology Dispensary"
city: Zaporizhzhia
country: Ukraine
facility: 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
city: London
country: United Kingdom
facility: Royal Marsden Hospital London
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital Surrey
Study officials:
References: