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An Umbrella Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Gastric or Gastroesophageal Junction Carcinoma

Primary Purpose

Gastric and Gastroesophageal Junction Carcinoma

Status
Active
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Atezolizumab
Capecitabine
Oxaliplatin
Tiragolumab
AB011
Sponsored by
Hoffmann-La Roche
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Gastric and Gastroesophageal Junction Carcinoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria for Stage 1:

  • ECOG Performance Status of 0 or 1
  • Inoperable locally advanced, metastatic, or advanced GC or GEJC, with adenocarcinoma confirmed as the predominant histology
  • No prior systemic treatment for advanced or metastatic disease
  • Life expectancy >= 3 months, as determined by the investigator
  • Human epidermal growth factor receptor 2 (HER2)-negative tumors
  • Measurable disease according to RECIST v1.1
  • Adequate hematologic and end-organ function
  • Patients without hepatitis B virus (HBV) infection at screening
  • Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening
  • Negative HIV test at screening
  • For women of childbearing potential: agreement to remain abstinent or use contraception, and agreement to refrain from donating eggs, as outlined for each specific treatment arm
  • For men: agreement to remain abstinent or use contraception, and agreement to refrain from donating sperm, as outlined for each specific treatment arm

Exclusion Criteria for Stage 1:

  • Prior treatment with CD137 agonists or immune checkpoint blockade therapies
  • Treatment with investigational therapy within 28 days prior to initiation of study treatment
  • Any contraindications to any of the study drugs of the chemotherapy regimen
  • Eligible only for the control arm
  • Patients with a signet ring cells dominant carcinoma
  • Symptomatic, untreated, or actively progressing CNS metastases
  • History of leptomeningeal disease
  • Active or history of autoimmune disease or immune deficiency
  • Significant cardiovascular disease within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina
  • History of malignancy other than GC or GEJC within 2 years prior to initiation of study treatment, with the exception of malignancies with a negligible risk of metastasis or death

Exclusion Criteria for Tiragolumab-Containing Arm:

  • Prior treatment with an anti-TIGIT agent
  • Active Epstein-Barr virus (EBV) infection or known or suspected chronic active EBV infection at screening

Sites / Locations

  • The General Hospital of People?s Liberation Army (301 Hospital)
  • the First Hospital of Jilin University
  • First Affiliated Hospital of Gannan Medical University
  • The Sixth Affiliated Hospital of Sun Yat-sen University
  • The First Affiliated Hospital, Zhejiang University
  • Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
  • Harbin Medical University Cancer Hospital
  • The Second Affiliated Hospital of Anhui Medical University
  • Affiliated Hopsital of Jining Medical University
  • Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School
  • Nan Tong Tumor Hospital
  • Shanxi Province Cancer Hospital
  • The First Affiliated Hospital of Xian Jiao Tong University
  • The First Affiliated Hospital of Zhengzhou University

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Active Comparator

Experimental

Experimental

Active Comparator

Arm Label

Atezo + CAPOX (capecitabine + oxaliplatin)

Atezo + CAPOX +Tir

Atezo + CAPOX + AB011

CAPOX + AB011

Arm Description

Participants in the atezolizumab plus capecitabine plus oxaliplatin in Stage 1 will receive treatment until unacceptable toxicity or loss of clinical benefit as determined by the investigator.

Participants in the atezolizumab plus capecitabine plus oxaliplatin plus tiragolumab arm in Stage 1 will receive treatment until unacceptable toxicity or loss of clinical benefit as determined by the investigator.

Participants in the atezolizumab plus capecitabine plus oxaliplatin plus AB011 arm in Stage 1 will receive treatment until unacceptable toxicity or loss of clinical benefit as determined by the investigator.

Participants in the capecitabine plus oxaliplatin plus AB011 arm in Stage 1 will receive treatment until unacceptable toxicity or loss of clinical benefit as determined by the investigator.

Outcomes

Primary Outcome Measures

Objective Response Rate (ORR)
ORR is defined as the proportion of participants with a complete response or a partial response on two consecutive occasions >= 4 weeks apart during Stage 1, as determined by the investigator according to RECIST v1.1.

Secondary Outcome Measures

Progression-Free Survival (PFS)
PFS after randomization is defined as the time from randomization to the first occurrence of disease progression or death from any cause (whichever occurs first) in Stage 1, as determined by the investigator according to RECIST v1.1.
Overall Survival (OS)
OS after randomization, defined as the time from randomization to death from any cause, regardless of stage.
Overall Survival (OS)
OS at specific timepoints.
Duration of Response (DOR)
DOR is defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first) in Stage 1, as determined by the investigator according to RECIST v1.1.
Disease Control Rate
Disease control rate is defined as the proportion of participants with stable disease for >= 12 weeks or a complete or a partial response, as determined by the investigator according to RECIST v1.1.
Percentage of Participants with Adverse Events in Stage 1
Percentage of participants with adverse events in Stage 1.
Percentage of Participants with Adverse Events in Stage 2
Percentage of participants with adverse events in Stage 2.

Full Information

First Posted
February 9, 2022
Last Updated
September 27, 2023
Sponsor
Hoffmann-La Roche
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1. Study Identification

Unique Protocol Identification Number
NCT05251948
Brief Title
An Umbrella Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Gastric or Gastroesophageal Junction Carcinoma
Official Title
A Phase Ib/II, Open-Label, Multicenter, Randomized Umbrella Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Gastric or Gastroesophageal Junction Carcinoma (MORPHEUS C-Gastric and Gastroesophageal Junction Carcinoma)
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
March 1, 2022 (Actual)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
June 22, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No

5. Study Description

Brief Summary
This is a Phase Ib/II, open-label, multicenter, randomized umbrella study in participants with advanced gastric carcinoma (GC) or gastroesophageal junction carcinoma (GEJC). The study is designed with the flexibility to open new treatment arms as new treatments become available, close existing treatment arms that demonstrate minimal clinical activity or unacceptable toxicity, and modify the participant population. Cohort 1 will enroll participants with inoperable locally advanced, metastatic, or advanced GC or GEJC, with adenocarcinoma confirmed as the predominant histology, who have not received prior systemic therapy for advanced or metastatic disease. Eligible participants will initially be randomly assigned to one of treatment arms (Stage 1). Participants who experience loss of clinical benefit or unacceptable toxicity during Stage 1 may be eligible to receive treatment with a different treatment combination (Stage 2). When a Stage 2 treatment combination is available, this will be introduced by amending the protocol.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Gastric and Gastroesophageal Junction Carcinoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
255 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Atezo + CAPOX (capecitabine + oxaliplatin)
Arm Type
Active Comparator
Arm Description
Participants in the atezolizumab plus capecitabine plus oxaliplatin in Stage 1 will receive treatment until unacceptable toxicity or loss of clinical benefit as determined by the investigator.
Arm Title
Atezo + CAPOX +Tir
Arm Type
Experimental
Arm Description
Participants in the atezolizumab plus capecitabine plus oxaliplatin plus tiragolumab arm in Stage 1 will receive treatment until unacceptable toxicity or loss of clinical benefit as determined by the investigator.
Arm Title
Atezo + CAPOX + AB011
Arm Type
Experimental
Arm Description
Participants in the atezolizumab plus capecitabine plus oxaliplatin plus AB011 arm in Stage 1 will receive treatment until unacceptable toxicity or loss of clinical benefit as determined by the investigator.
Arm Title
CAPOX + AB011
Arm Type
Active Comparator
Arm Description
Participants in the capecitabine plus oxaliplatin plus AB011 arm in Stage 1 will receive treatment until unacceptable toxicity or loss of clinical benefit as determined by the investigator.
Intervention Type
Drug
Intervention Name(s)
Atezolizumab
Other Intervention Name(s)
Tecentriq
Intervention Description
Atezolizumab is administered by IV infusion on Day 1 of each 21 day cycle. Treatment until progressive disease.
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Intervention Description
Capecitabine is administered orally twice daily on Days 1-14 of each 21 day cycle. Treatment for up to six cycles.
Intervention Type
Drug
Intervention Name(s)
Oxaliplatin
Intervention Description
Oxaliplatin is administered by IV infusion on Day 1 of each 21 day cycle. Treatment for up to six cycles.
Intervention Type
Drug
Intervention Name(s)
Tiragolumab
Intervention Description
Tiragolumab is administered by IV infusion on Day 1 of each 21 day cycle.
Intervention Type
Drug
Intervention Name(s)
AB011
Intervention Description
AB011 is administered by IV infusion on Day 1 of each 21 day cycle. Treatment until progressive disease.
Primary Outcome Measure Information:
Title
Objective Response Rate (ORR)
Description
ORR is defined as the proportion of participants with a complete response or a partial response on two consecutive occasions >= 4 weeks apart during Stage 1, as determined by the investigator according to RECIST v1.1.
Time Frame
Up to approximately 3-5 years
Secondary Outcome Measure Information:
Title
Progression-Free Survival (PFS)
Description
PFS after randomization is defined as the time from randomization to the first occurrence of disease progression or death from any cause (whichever occurs first) in Stage 1, as determined by the investigator according to RECIST v1.1.
Time Frame
Randomization to the first occurrence of disease progression or death from any cause (whichever occurs first) (up to approximately 3-5 years)
Title
Overall Survival (OS)
Description
OS after randomization, defined as the time from randomization to death from any cause, regardless of stage.
Time Frame
Randomization to death from any cause (up to approximately 3-5 years)
Title
Overall Survival (OS)
Description
OS at specific timepoints.
Time Frame
At specific timepoints (up to approximately 3-5 years)
Title
Duration of Response (DOR)
Description
DOR is defined as the time from the first occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first) in Stage 1, as determined by the investigator according to RECIST v1.1.
Time Frame
First occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first) (up to approximately 3-5 years)
Title
Disease Control Rate
Description
Disease control rate is defined as the proportion of participants with stable disease for >= 12 weeks or a complete or a partial response, as determined by the investigator according to RECIST v1.1.
Time Frame
Up to approximately 3-5 years
Title
Percentage of Participants with Adverse Events in Stage 1
Description
Percentage of participants with adverse events in Stage 1.
Time Frame
Baseline through approximately end of study (approximately 3-5 years)
Title
Percentage of Participants with Adverse Events in Stage 2
Description
Percentage of participants with adverse events in Stage 2.
Time Frame
Baseline through approximately end of study (approximately 3-5 years)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria for Stage 1: ECOG Performance Status of 0 or 1 Inoperable locally advanced, metastatic, or advanced GC or GEJC, with adenocarcinoma confirmed as the predominant histology No prior systemic treatment for advanced or metastatic disease Life expectancy >= 3 months, as determined by the investigator Human epidermal growth factor receptor 2 (HER2)-negative tumors Measurable disease according to RECIST v1.1 Adequate hematologic and end-organ function Patients without hepatitis B virus (HBV) infection at screening Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening Negative HIV test at screening For women of childbearing potential: agreement to remain abstinent or use contraception, and agreement to refrain from donating eggs, as outlined for each specific treatment arm For men: agreement to remain abstinent or use contraception, and agreement to refrain from donating sperm, as outlined for each specific treatment arm Exclusion Criteria for Stage 1: Prior treatment with CD137 agonists or immune checkpoint blockade therapies Treatment with investigational therapy within 28 days prior to initiation of study treatment Any contraindications to any of the study drugs of the chemotherapy regimen Eligible only for the control arm Patients with a signet ring cells dominant carcinoma Symptomatic, untreated, or actively progressing CNS metastases History of leptomeningeal disease Active or history of autoimmune disease or immune deficiency Significant cardiovascular disease within 3 months prior to initiation of study treatment, unstable arrhythmia, or unstable angina History of malignancy other than GC or GEJC within 2 years prior to initiation of study treatment, with the exception of malignancies with a negligible risk of metastasis or death Exclusion Criteria for Tiragolumab-Containing Arm: Prior treatment with an anti-TIGIT agent Active Epstein-Barr virus (EBV) infection or known or suspected chronic active EBV infection at screening
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
The General Hospital of People?s Liberation Army (301 Hospital)
City
Beijing City
ZIP/Postal Code
100080
Country
China
Facility Name
the First Hospital of Jilin University
City
Changchun
ZIP/Postal Code
130021
Country
China
Facility Name
First Affiliated Hospital of Gannan Medical University
City
Ganzhou
ZIP/Postal Code
341000
Country
China
Facility Name
The Sixth Affiliated Hospital of Sun Yat-sen University
City
Guangzhou
ZIP/Postal Code
510655
Country
China
Facility Name
The First Affiliated Hospital, Zhejiang University
City
Hangzhou City
ZIP/Postal Code
310003
Country
China
Facility Name
Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
City
Hangzhou
ZIP/Postal Code
310016
Country
China
Facility Name
Harbin Medical University Cancer Hospital
City
Harbin
ZIP/Postal Code
150081
Country
China
Facility Name
The Second Affiliated Hospital of Anhui Medical University
City
Hefei
ZIP/Postal Code
230601
Country
China
Facility Name
Affiliated Hopsital of Jining Medical University
City
Jining
ZIP/Postal Code
272000
Country
China
Facility Name
Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School
City
Nanjing City
ZIP/Postal Code
210008
Country
China
Facility Name
Nan Tong Tumor Hospital
City
Nantong City
ZIP/Postal Code
226361
Country
China
Facility Name
Shanxi Province Cancer Hospital
City
Taiyuan City
ZIP/Postal Code
030013
Country
China
Facility Name
The First Affiliated Hospital of Xian Jiao Tong University
City
Xi'an City
ZIP/Postal Code
710061
Country
China
Facility Name
The First Affiliated Hospital of Zhengzhou University
City
Zhengzhou
ZIP/Postal Code
450052
Country
China

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here ( https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Learn more about this trial

An Umbrella Study Evaluating the Efficacy and Safety of Multiple Treatment Combinations in Patients With Gastric or Gastroesophageal Junction Carcinoma

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