Neoplasms

All Conditions

Digestive System Diseases

Symptoms and General Pathology

Rare Diseases

Adenocarcinoma

Stomach Neoplasms

Neoplasm Metastasis

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Stomach Cancer

Antineoplastic Agents

All Drugs and Chemicals

Oxaliplatin

Capecitabine

Antimetabolites

Subjects enrolled are treated with oral capecitabine 1000mg per m2 bid for two weeks（every 3 weeks）and intravenous oxaliplatin 130mg per m2（every 3 weeks）in combination with sintilimab 200mg (every 3 weeks)

oral capecitabine 1000mg per m2 bid d1-14, intravenous oxaliplatin 130mg d1 per m2, sintilimab 200mg (every 3 weeks)

sintilimab

Qiu Li, M.D.

This study aims to evaluate the efficacy and safety of Sintilimab plus CAPOX in the conversion therapy for patients with unresectable locally advanced or limited metastatic adenocarcinoma of the stomach or esophagogastric junction

In a variety of solid tumors such as colorectal cancer, it has been confirmed that some selected advanced patients still have a chance to cure through multidisciplinary treatment. Because of the poor biological behavior of gastric cancer, few people with advanced gastric cancer can benefit from local treatment, and there are fewer related studies. However, retrospective and small sample size prospective phase II clinical studies have also shown that unresectable locally advanced and some selected limited distant metastatic gastric and gastric junction adenocarcinoma patients may also achieve long-term survival through multimodal treatment strategies. The triple drug regimens were often used as conversion regimens in previous studies. Although the efficiency was improved, the R0 resection rate was only about 60%, the disease-free survival was about 10 months, and the toxicity was high. In order to improve the survival of these patients, more effective and less toxic treatment regimens are urgently needed. Objective response rate was 76.5% with anti-PD-1 antibody nivolumab plus CapeOX. The investigators predict that this regimen will achieve good results in the conversion treatment of advanced gastric cancer. The investigators intend to carry out this study to evaluate the efficacy and safety of Sintilimab plus CAPOX in the conversion therapy for patients with unresectable locally advanced or limited metastatic adenocarcinoma of the stomach or esophagogastric junction. The primary objectives are 12-month progression- free survival (PFS) rate. Secondary objectives include safety, objective response rate (ORR), R0 resection rate , tumor regression grading（TRG）, progression- free survival (PFS) ，overall survival (OS) and exploratory biomarker assessment. Subjects enrolled are treated with oral capecitabine 1000mg per m2 bid for two weeks（every 3 weeks）and intravenous oxaliplatin 130mg per m2（every 3 weeks）in combination with sintilimab 200mg (every 3 weeks) for 3 cycles. After 3 cycles of treatment, the tumor was evaluated. The clinical efficacy was evaluated as CR\\PR\\SD. Patients with SD,PR,CR will be treated with surgery. 36 patients will be included in this study

Conversion Therapy With Sintilimab Plus CAPOX in Patients With Unresectable Locally Advanced or Limited Metastatic Adenocarcinoma of the Stomach or Esophagogastric Junction

An Exploratory Study of Conversion Therapy With Sintilimab Plus CAPOX in Patients With Unresectable Locally Advanced or Limited Metastatic Adenocarcinoma of the Stomach or Esophagogastric Junction

Proportion of patients with Progression Free Survival in 12-month

Proportion of patients whose tumor volume has reached a predetermined value and can maintain a minimum time limit, including complete response and partial response patients

Proportion of patients with complete resection

Assessing the grade of tumor regression according to tumor regression grading criteria

Defined as the time from the date of enrollment to the first date of documented objective progression disease (defined by RECIST 1.1) or of death from any cause

Defined as the time from the date of enrollment to the date of death from any cause

Any adverse events related with treatment with Sintilimab plus CAPOX

Sichuan University

Professor

Preoperative treatment：130mg/m2，iv, 2h，d1，Q3W; Postoperative treatment：130mg/m2，iv, 2h，d1，Q3W;

Preoperative treatment：1000 mg /m2, PO，bid d1-14，Q3W； Postoperative treatment：1000 mg /m2, PO，bid. d1-14，Q3W；

Cadonilimab

Xuewei Ding, MD

The efficacy and safety of combination with Cadonilimab and CapeOX Regimen for neoadjuvant treatment of resectable locally advanced adenocarcinoma of the gastro-esophageal junction.

This study was a single arm, open-label, single-center clinical study to evaluate the efficacy and safety of combination with Cadonilimab and CapeOX Regimen for neoadjuvant treatment of resectable locally advanced adenocarcinoma of the gastro-esophageal junction.

Cadonilimab Combined With CapeOX Regimen in Perioperative Treatment of Resectable Locally Advanced Gastric Cancer

Single-arm, Open-label, Single-center Phase II Clinical Study of Cadonilimab Combined With CapeOX Regimen in Perioperative Treatment of Resectable Locally Advanced Gastric Cancer

Pathological complete response (pCR) rate is defined as the proportion of participants whose tumor in the stomach and lymph node completely disappeared, as determined by a pathologist.

3 years disease-free survival (DFS) rate is defined as proportion of participants who have no recurrence or metastasis after 3 years of radical treatment

Major pathological response (MPR) rate is defined as the proportion of participants whose percentage of residual tumor in the stomach and lymph node decreased to \< 10%, as determined by a pathologist

Overall response rate ( ORR) is defined as proportion of participants who have a best response of CR or PR

Disease Control Rate (DCR) is defined as proportion of participants who have a best response of CR#PR or SD

Defined as the proportion of patients with AE, treatment-related AE (TRAE), immune-related AE (irAE), serious adverse event (SAE), assessed by NCI CTCAE v5.0

Tianjin Medical University Cancer Institute and Hospital

Esophageal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Head and Neck Neoplasms

Esophageal Diseases

Esophageal Cancer

Antibodies

Antibodies, Monoclonal

Irinotecan

Immunoglobulins

Ramucirumab

Topoisomerase I Inhibitors

Enzyme Inhibitors

Angiogenesis Inhibitors

Growth Inhibitors

Patients receive ramucirumab IV over 30 minutes and MM-398 IV over 90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Liposomal Irinotecan

Quality-of-Life Assessment

Questionnaire Administration

Afsaneh Barzi, MD

This phase I/II trial studies the side effects and best dose of MM-398 and ramucirumab in treating patients with gastric cancer or gastroesophageal junction adenocarcinoma. MM-398 contains a chemotherapy drug called irinotecan, which in its active form interrupts cell reproduction. MM-398 builds irinotecan into a container called a liposome which may be able to release the medicine slowly over time to reduce side effects and increase its ability to kill tumor cells. Immunotherapy with monoclonal antibodies, such as ramucirumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving MM-398 and ramucirumab together may work better in treating patients with gastric cancer or gastroesophageal junction adenocarcinoma.

PRIMARY OBJECTIVES:

I. Phase I portion is to determine the recommended phase II dose (RP2D) of liposomal irinotecan (MM-398) when given in combination with ramucirumab at 8 mg/kg every 2 weeks in patients with gastric and gastroesophageal adenocarcinoma (GEAC) who had failed or are intolerant of platinum-based therapy.

II. Phase II portion is to assess the preliminary efficacy and tolerability of MM-398 in combination with ramucirumab in patients with GEAC who had failed or are intolerant of platinum based therapy.

SECONDARY OBJECTIVES:

I. To estimate the best overall response rate through up to three cycles of therapy among patients with measurable disease at study entry.

II. To assess the incidence and severity of toxicity of the combination.

EXPLORATORY OBJECTIVES:

I. Descriptive of quality of life domains using Patient-Reported Outcomes Measurement Information System (PROMIS) global health instrument (PRO).

II. Descriptive of altered genes on liquid biopsies. III. To assess the effect of the anti-angiogenic ramucirumab on distribution of MM-398 via magnetic resonance imaging (MRI) with and without ferumoxytol.

OUTLINE: This is a phase I, dose escalation study of MM-398followed by a phase II study.

Patients receive ramucirumab intravenously (IV) over 30 minutes and MM-398 IV over 90 minutes on days 1 and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for up to 6 months.

MM-398 and Ramucirumab in Treating Patients With Gastric Cancer or Gastroesophageal Junction Adenocarcinoma

Phase I/II Study of MM-398 in Combination With Ramucirumab After Platinum Failure in Gastric Cancer

DLT is defined as follows: For hematological toxicity: Drug-related grade 4 neutropenia for more than 5 days without fever or infection; Grade 4 neutropenia of any duration accompanied by fever or infection, Grade 4 thrombocytopenia. For non-hematological toxicity: All grade 3-4 that represents a 2 grade increase over baseline, excluding: Untreated or inadequately treated nausea, vomiting, diarrhea lasting shorter than 24 hours; Alopecia; Grade 3 fatigue that returns to grade 2 or less within 7 days; Grade 3 laboratory abnormalities that are not considered clinically significant and that return to grade 2 or less within 72 hours.

PFS will be calculated from treatment start date to date of disease progression or date of death due to any cause, or to the time of last follow-up, whichever occurs first.

BOR will be evaluated from start of treatment until progression/recurrence.

Analyses of safety/toxicity will be performed for all patients having received at least one dose of study drug.

National Cancer Institute (NCI)

Ipsen

University of Southern California

Stomach Diseases

Anti-Infective Agents

Paclitaxel

Albumin-Bound Paclitaxel

Trifluridine

Lexatumumab

Antineoplastic Agents, Immunological

Immunoglobulins, Intravenous

Tubulin Modulators

Antimitotic Agents

Immunologic Factors

Antiviral Agents

Patients receive TAS-102 PO BID on days 1-5 and 8-12, and ramucirumab IV over 30-60 minutes on days 1 and 15. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity.

Patients receive paclitaxel IV over 1-96 hours on days 1, 8, and 15, and ramucirumab IV over 30-60 minutes on days 1 and 15. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity.

Trifluridine and Tipiracil Hydrochloride

Darryl A. Outlaw

ACCRU Operations

Mohamad B. Sonbol

Syma Iqbal

Jason S. Starr

Arun Nagarajan

Pashtoon M. Kasi

Clinical Trial Information Program

Michael Gibson

Anthony J. Jaslowski

Mohamad B Sonbol

This phase II trial studies the effect of the combination of ramucirumab and trifluridine/tipiracil or paclitaxel in treating patients with previously treated gastric or gastroesophageal junction cancer that has spread to other places in the body (advanced). Ramucirumab may damage tumor cells by targeting new blood vessel formation. Trifluridine/tipiracil is a chemotherapy pill and that may damage tumor cells by damaging their deoxyribonucleic acid (DNA). Paclitaxel may block cell growth by stopping cell division which may kill tumor cells. Giving ramucirumab and trifluridine/tipiracil will not be worse than ramucirumab and paclitaxel in treating gastric or gastroesophageal junction cancer.

PRIMARY OBJECTIVE:

I. To compare, in a non-inferiority fashion, the progression-free survival (PFS) in patients with metastatic refractory gastric/gastroesophageal junction (GEJ) adenocarcinoma receiving the combination of ramucirumab with trifluridine and tipiracil hydrochloride (TAS-102) versus (vs.) paclitaxel and ramucirumab.

SECONDARY OBJECTIVES:

I. To assess overall survival (OS) in this patient population for each regimen. II. Assess changes in patient quality of life (QOL) as measured by the linear analogue self-assessment (LASA) questionnaire for each regimen.

III. To determine the safety of the combination of ramucirumab with TAS-102 in this patient population.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM A: Patients receive TAS-102 orally (PO) twice daily (BID) on days 1-5 and 8-12, and ramucirumab intravenously (IV) over 30-60 minutes on days 1 and 15. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity.

ARM B: Patients receive paclitaxel IV over 1-96 hours on days 1, 8, and 15, and ramucirumab IV over 30-60 minutes on days 1 and 15. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30-35 days, then every 3 months for up to 3 years.

Ramucirumab and Trifluridine/Tipiracil or Paclitaxel for the Treatment of Patients With Previously Treated Advanced Gastric or Gastroesophageal Junction Cancer

Ramucirumab Plus Trifluridine/Tipiracil (TAS-102) for Patients With Previously Treated Advanced Gastric or Gastroesophageal Junction Adenocarcinoma: An Investigator-Initiated, Randomized Non-Inferiority Phase 2 Study

Progression free survival is defined as the time interval between randomization date and the date of disease progression or death (referred to as an "event"), whichever occurs first. Disease progression will be determined based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. The median progression free survival will be estimated using the Kaplan-Meier method for each arm, corresponding 95% confidence intervals, and hazard ratio comparing the treatment arm to the control arm will be reported.

Median OS will be estimated using the Kaplan-Meier method. Patients who do not experience death while on study will be censored at the last known date alive. The median OS and corresponding 95% confidence interval will be reported by arm.

Patient reported QOL outcomes will be collected using the Linear Analog Self-Assessment (LASA) Questionnaire. Data will be collected each cycle. Mean values of the first question (regarding overall QOL) at each cycle will be plotted, and stratified by arm.

Adverse events will be recorded using Common Terminology Criteria for Adverse Events version 5.0. The proportion of patients who experience a grade 3+ adverse event at least possibly related to treatment will be reported by arm.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Conversion Therapy With Sintilimab Plus CAPOX in Patients With Unresectable Locally Advanced or Limited Metastatic Adenocarcinoma of the Stomach or Esophagogastric Junction	NCT04263870	Gastroesophagea... Stomach Adenoca... Locally Advance... Metastatic Gast...	sintilimab	18 Years - 75 Years	Sichuan University
Cadonilimab Combined With CapeOX Regimen in Perioperative Treatment of Resectable Locally Advanced Gastric Cancer	NCT05974059	Locally Advance...	Oxaliplatin Capecitabine Cadonilimab	18 Years - 75 Years	Tianjin Medical University Cancer Institute and Hospital
MM-398 and Ramucirumab in Treating Patients With Gastric Cancer or Gastroesophageal Junction Adenocarcinoma	NCT03739801	Locally Advance... Metastatic Gast... Metastatic Unre... Unresectable Ga... Gastric Adenoca... Gastroesophagea...	Liposomal Irino... Quality-of-Life... Questionnaire A... Ramucirumab	18 Years -	University of Southern California
MM-398 and Ramucirumab in Treating Patients With Gastric Cancer or Gastroesophageal Junction Adenocarcinoma	NCT03739801	Locally Advance... Metastatic Gast... Metastatic Unre... Unresectable Ga... Gastric Adenoca... Gastroesophagea...	Liposomal Irino... Quality-of-Life... Questionnaire A... Ramucirumab	18 Years -	University of Southern California
Ramucirumab and Trifluridine/Tipiracil or Paclitaxel for the Treatment of Patients With Previously Treated Advanced Gastric or Gastroesophageal Junction Cancer	NCT04660760	Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Clinical Stage ... Locally Advance... Locally Advance... Metastatic Gast... Metastatic Gast... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Pathologic Stag... Postneoadjuvant... Postneoadjuvant... Postneoadjuvant... Postneoadjuvant... Postneoadjuvant... Postneoadjuvant... Postneoadjuvant... Postneoadjuvant...	Paclitaxel Quality-of-Life... Ramucirumab Trifluridine an...	18 Years -	Academic and Community Cancer Research United

Spots Global Cancer Trial Database for locally advanced unresectable gastric adenocarcinoma