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

Gastric Cancer Clinical Trial

— ANGEL  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03042611
• Other study ID #: LSK-AM301
• Status: Completed
• Phase: Phase 3
• Start date: March 14, 2017
• Est. completion date: September 23, 2020

Study information

• Verified date: June 2022
• Source: Elevar Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 460
• Est. completion date: September 23, 2020
• Est. primary completion date: February 15, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Adenocarcinoma
• Gastric Adenocarcinoma
• Gastric Cancer
• Stomach Neoplasms

Intervention

Drug:
• Rivoceranib
Oral tablet
• Placebo
Oral tablet

Locations

Country	Name	City	State
France	Centre Hospitalier Franco-Britannique; Oncologie Médicale	Levallois-Perret
France	Centre Leon-Berard (CLB)	Lyon
France	Institut Regional du Cancer Montpellier (ICM)	Montpellier
France	Centre Antoine-Lacassagne	Nice
France	Institut Gustave Roussy	Villejuif
Germany	Charite - Universitaetsmedizin Berlin - Medizinische Klinik mit Schwerpunkt Haematologie, Onkologie und Tumorimmunologie	Berlin
Germany	"Institut für Klinisch-Onkologische Forschung (IKF) Krankenhaus Nordwest gGmbH UCT - Universitäres Centrum für Tumorerkrankungen Frankfurt	Frankfurt
Germany	Facharztzentrum Eppendorf - Haematologisch-Onkologische Praxis Eppendorf (HOPE)	Hamburg
Germany	Universitätsklinik Marburg, Klinik fur Innere Medizin, Schwerpunkt Haematologie, Onkologie und Immunologie	Marburg
Italy	Magna Graecia University- Department of Experimental and Clinical Medicine	Catanzaro
Italy	U.O Di Oncologia Ospedale Degli Infermi	Faenza
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	Ospedale "Felice Lotti"	Pontedera
Italy	IRCCS/Arcispedale Santa Maria Nuova	Reggio Emilia
Italy	Rimini Hospital	Rimini
Italy	Ospedali Riuniti di Ancona - SOD Clinica Oncologica	Torrette
Japan	Chiba Cancer Center	Chiba	Chiba City
Japan	National Cancer Center Hospital East	Chiba	Kashiwa
Japan	National Hospital Organization Shikoku Cancer Center	Ehime	Matsuyama
Japan	Japan Community Health Care Organization Kyushu Hospital	Fukuoka	Kitakyushu-shi
Japan	Kyushu University Hospital	Fukuoka	Higashi-ku
Japan	Hokkaido University Hospital	Hokkaido	Sapporo
Japan	Hyogo Cancer Center	Hyogo	Akasi-city
Japan	St. Marianna University School of Medicine Hospital	Kanagawa	Kawasaki-shi
Japan	Saku Central Hospital Advanced Care Center	Nagano	Saku-shi
Japan	Aichi Cancer Center Hospital	Nagoya
Japan	Osaka University Hospital	Osaka	Suita
Japan	Saitama Cancer Center	Saitama	Kitaadachi-gun
Japan	Keio University Hospital	Tokyo	Shinjuku-ku
Japan	National Cancer Center Hospital	Tokyo	Chuo-ku
Japan	The Cancer Institute Hospital of Japanese Foundation For Cancer Research	Tokyo	Koto-ku
Korea, Republic of	Hallym University Sacred Heart Hospital	Anyang-si	Gyeonggi-do
Korea, Republic of	Dong-A University Hospital	Busan
Korea, Republic of	Inje University Haeundae Paik Hospital	Busan
Korea, Republic of	Pusan National University Hospital	Busan
Korea, Republic of	Chungbuk National University Medical Center	Chuncheon
Korea, Republic of	Chungbuk National University Hospital	Chungbuk
Korea, Republic of	Keimyung University Dongsan Medical Center	Daegu
Korea, Republic of	Kyungpook National University Medical Center	Daegu
Korea, Republic of	Yeungnam University Medical Center	Daegu
Korea, Republic of	Chungnam National University Hospital	Daejeon
Korea, Republic of	National Cancer Center	Goyang-si	Gyeonggi-do
Korea, Republic of	Seoul National University Bundang Hospital	Gyeonggi-do
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 Anam Hospital	Seoul
Korea, Republic of	Korea University Guro Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Severence Hospital, Yonsei University Health System	Seoul
Korea, Republic of	Veterans Health Service (VHS) Medical Center	Seoul
Korea, Republic of	Ajou University Hospital	Suwon-si	Gyonggi-do
Korea, Republic of	Ulsan University Hospital	Ulsan
Poland	Szpital Uniwersytecki w Krakowie, Odzial Kliniczny Onkologii	Kraków
Poland	Centrum Onkologii-Instytut im. Marii Sklodowskiej-Curie, Klinika Gastroenterologii Onkologicznej	Warszawa
Romania	Saint Constantin Hospital (TEO HEALTH SA)	Brasov
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	Centrul de Oncologie "Sf. Nectarie", Sectia de Oncologie Medicala	Craiova
Russian Federation	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	State Budgetary Healthcare Institution of Stavropol Territory "Pyatigorsk Oncology Dispensary"	Pyatigorsk
Russian Federation	Ogarev Mordovia State University	Saransk
Russian Federation	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	State Budgetary Healthcare Institution "Republican Clinical Oncology Dispensary"	Ufa
Taiwan	Chang Gung Memorial Hospital - Kaohsiung Branch	Kaohsiung	Niaosong Dist
Taiwan	Kaohsiung Medical University Hospital	Kaohsiung	Sanmin Dist
Taiwan	China Medical University Hospital	Taichung	Taichung City
Taiwan	Chi Mei Medical Center - LiouYing Branch	Tainan	Liuying DIst
Taiwan	National CHeng Kung University Hospital	Tainan	Tainan City
Taiwan	National Taiwan University Hospital	Taipei	Zhongzheng Dist
Taiwan	Taipei Veterans General Hospital	Taipei	Beitou Dist
Taiwan	Chang Gung Memorial Hospital - Linko Branch	Taoyuan	Kuei Shan Hsiang
Ukraine	Dnipropetrovsk Medical Academy, Department of Oncology	Dnipro
Ukraine	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	Kherson Regional Oncological Dispensary	Kherson
Ukraine	Municipal Institution Kryvyi Rig Oncology Dispensary", Chemotherapy Department	Kryvyi Rih
Ukraine	Municipal Institution "Kyiv City Clinical Oncological Center"	Kyiv
Ukraine	Communal Institution "Transcarpathian Regional Clinical Oncological Center"	Uzhhorod
Ukraine	Communal Institution "Vinnytsia Regional Clinical Oncology Dispensary"	Vinnytsia
Ukraine	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
United Kingdom	Royal Marsden Hospital London	London
United Kingdom	The Christie NHS Foundation Trust	Manchester
United Kingdom	Royal Marsden Hospital Surrey	Sutton
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	Hudson Valley Cancer Centre	Hawthorne	New York
United States	Mayo Clinic Cancer Center	Rochester	Minnesota
United States	Highlands Oncology Group	Rogers	Arkansas
United States	Mayo Clinic Phoenix	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Elevar Therapeutics

Countries where clinical trial is conducted

United States,  France,  Germany,  Italy,  Japan,  Korea, Republic of,  Poland,  Romania,  Russian Federation,  Taiwan,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS)	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	Progression-free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)	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
Secondary	Objective Response Rate (ORR) Per RECIST 1.1	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
Secondary	Disease Control Rate (DCR)	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
Secondary	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)	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)
Secondary	Change From Baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-Stomach Cancer Specific (EORTC QLQ-STO22) Score	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)
Secondary	Change From Baseline in EuroQol 5-Dimension 5-Level Visual Analogue Scale (EQ-5D-5L VAS) Score	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)
Secondary	Number of Participants Per QOL Dimension Response as Measured by the EuroQol 5-Dimension 5-Level (EQ-5D-5L) Questionnaire	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)