Clinical trial NCT05251948: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Gastric and Gastroesophageal Junction Carcinoma
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2022-02-23
Enrollment: 40
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: 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.


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

Primary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Up to approximately 3-5 years
Secondary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: Randomization to the first occurrence of disease progression or death from any cause (whichever occurs first) (up to approximately 3-5 years)
measure: Overall Survival (OS)
timeFrame: Randomization to death from any cause (up to approximately 3-5 years)
measure: Overall Survival (OS)
timeFrame: At specific timepoints (up to approximately 3-5 years)
measure: Duration of Response (DOR)
timeFrame: First occurrence of a documented objective response to disease progression or death from any cause (whichever occurs first) (up to approximately 3-5 years)
measure: Disease Control Rate
timeFrame: Up to approximately 3-5 years
measure: Percentage of Participants with Adverse Events in Stage 1
timeFrame: Baseline through approximately end of study (approximately 3-5 years)
measure: Percentage of Participants with Adverse Events in Stage 2
timeFrame: Baseline through approximately end of study (approximately 3-5 years)
Other outcomes:
Locations:
city: Beijing City
country: China
facility: The General Hospital of People?s Liberation Army (301 Hospital)
city: Changchun
country: China
facility: the First Hospital of Jilin University
city: Ganzhou
country: China
facility: First Affiliated Hospital of Gannan Medical University
city: Hangzhou City
country: China
facility: The First Affiliated Hospital, Zhejiang University
city: Hangzhou
country: China
facility: Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University
city: Hefei
country: China
facility: The Second Affiliated Hospital of Anhui Medical University
city: Jining
country: China
facility: Affiliated Hopsital of Jining Medical University
city: Nanjing City
country: China
facility: Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School
city: Nantong City
country: China
facility: Nan Tong Tumor Hospital
city: Taiyuan City
country: China
facility: Shanxi Province Cancer Hospital
city: Xi'an City
country: China
facility: The First Affiliated Hospital of Xian Jiao Tong University
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: