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

Study Overview
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Brief Summary
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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).

Official Title
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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

Conditions
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Gastric Cancer, Gastric Adenocarcinoma

Intervention / Treatment
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* Drug: Rivoceranib
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rivoceranib Plus BSC<br>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<br>* Oral tablet<br>* Other names: Apatinib;|
| Experimental: Placebo<br>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<br>* Oral tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 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) | 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 | 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) | 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) | 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 | 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 | 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 | 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gastric Cancer, Gastric Adenocarcinoma, Gastro-esophageal Cancer, Gastro-esophageal Junction Cancer, Stomach Cancer, Tumor, Oncology, Antiangiogenesis, Metastatic