Regorafenib Combined With Irinotecan as Second-line in Patients With Metastatic Gastro-oesophageal Adenocarcinomas (REGIRI)

October 13, 2023 updated by: UNICANCER

A Randomised Phase 2 Trial Assessing REGorafenib Combined With IRInotecan as Second-line Treatment in Patients With Metastatic Gastro-oesophageal Adenocarcinomas

Trial evaluating the efficacy of regorafenib combined with irinotecan compared to irinotecan alone in second-line treatment of patients with metastatic gastro-oesophageal adenocarcinomas.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Comparative interventional prospective phase 2, randomised, open-label, multicentric trial comparing the combination of regorafenib and irinotecan (REGIRI) to irinotecan alone (IRI) as second line treatment of patients with metastatic gastro-oesophageal adenocarcinomas.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
89

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Angers, France
        • Institut de Cancerologie de L'Ouest-Paul Papin
      • Brest, France
        • Hopital Morvan
      • Coudekerque-Branche, France
        • Clinique de Flandre
      • Dijon, France, 21079
        • Centre Georges François Leclerc
      • Levallois-Perret, France
        • Hôpital Franco-Britannique
      • Lille, France
        • Hopital Claude Huriez - CHU Lille
      • Limoges, France
        • CHU Dupuytren
      • Lyon, France
        • Centre Léon Bérard
      • Marseille, France
        • Hôpital de la Timone
      • Marseille, France
        • Institut Paoli Calmette
      • Montpellier, France, 34298
        • Institut Du Cancer Montpellier
      • Montpellier, France
        • Centre de Cancérologie du Grand Montpellier
      • Nice, France, 06189
        • Centre Antoine Lacassagne
      • Paris, France, 75015
        • Hôpital Europeén Georges Pompidou
      • Paris, France
        • GH Diaconesses Croix Saint-Simon
      • Perpignan, France
        • CH Saint Jean
      • Poitiers, France, 86000
        • CHU De Poitiers
      • Pringy, France
        • CH Annecy Genevois
      • Reims, France, 51100
        • Institut Jean Godinot
      • Reims, France
        • Hopital Robert Debre
      • Rouen, France
        • Hôpital Charles Nicolle
      • Saint-Grégoire, France
        • CHP Saint Grégoire
      • Saint-Herblain, France
        • Institut de Cancerologie de l'Ouest-Rene Gauducheau
      • Saint-Malo, France
        • CH Saint Malo
      • Strasbourg, France
        • Centre Paul Strass
      • Tours, France
        • Chru Tours
      • Vandœuvre-lès-Nancy, France, 54500
        • CHU Nancy - Hôpital Brabois

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Patient must have signed a written informed consent form prior to any study specific procedures
  2. Patients aged ≥18 years old
  3. Histologically confirmed diagnosis of gastro-oesophageal adenocarcinomas: gastroesophageal junction (Siewert II and III) and gastric adenocarcinomas
  4. Asymptomatic primary tumour
  5. Metastatic disease

  6. At least one target lesion (according to RECIST v1.1):

    • Unidimensionally measurable on cross-sectional imaging
    • In an area not previously irradiated
  7. Disease progression after a fluoropyrimidine and platinum agent-based chemotherapy (5-fluorouracil or 5-fluorouracil prodrugs combined with cisplatin or oxaliplatin). For example, docetaxel combined with FOLFOX, PD-L1/PD-1 inhibitors combined with FOLFOX, LV5-FU2-cisplatin or 5-fluorouracil-cisplatin are acceptable prior therapies.
  8. Eastern Cooperative Oncology Group (ECOG) performance status ≤1
  9. Life expectancy >3 months
  10. Amylase ≤1.5 x upper limit of normal (ULN) and lipase ≤1.5 x ULN

  11. Adequate liver function:

    • Total bilirubin ≤1.5 x ULN
    • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3.0 x ULN (≤5 x ULN for patients with liver metastasis)
    • Alkaline phosphatase (ALP) ≤2.5 x ULN (≤5.0 x ULN for patients with liver or bone metastases)
  12. Platelet count ≥100,000/mm³; haemoglobin (Hb) ≥9 g/dL; absolute neutrophil count (ANC) ≥1,500/mm³. The use of blood transfusion(s) to meet the inclusion criteria will not be allowed
  13. International normalised ratio (INR) ≤1.5 x ULN and partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) ≤1.5 x ULN unless receiving treatment with therapeutic anticoagulation. Patients being treated with anticoagulant, e.g., heparin, are eligible if there is no evidence of an underlying abnormality with these parameters and if a close monitoring of at least weekly evaluations was performed until INR and PTT are stable based on a pre-dose measurement as defined by the local standard of care
  14. Creatinine clearance (CLcr) ≥50 mL/min estimated by Cockcroft-Gault equation
  15. Women of childbearing potential and men must agree to use adequate contraception during the study and for at least 3 months after the last study drug administration
  16. Patients affiliated to the social security system

Exclusion Criteria:

  1. Symptomatic brain metastases or carcinomatous meningitis
  2. Bone-only metastasis
  3. Known and documented UGT1A1 deficiency
  4. History of Gilbert's syndrome
  5. Previous or concurrent cancer with a distinct primary site, other than gastro-oesophageal cancer, within 5 years prior to randomisation (except for curatively treated cervical cancer in situ, non-melanoma skin cancer, and superficial bladder tumours)
  6. Persistent proteinuria >3.5 g/24 h measured by urine protein-creatinine ratio from a random urine sample (grade ≥3, NCI-CTCAE v 5.0)
  7. Interstitial lung disease with ongoing signs and symptoms at inclusion
  8. Known hypersensitivity to any of the study drugs, study drug classes, or excipients
  9. Non-healing wound, non-healing ulcer, or non-healing bone fracture
  10. Patients with evidence or history of any bleeding diathesis, irrespective of severity
  11. Any haemorrhage or bleeding event grade ≥3 (NCI-CTCAE v.5.0) within 4 weeks before starting of the study treatment
  12. Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 6 month before starting the study treatment (except for adequately treated catheter-related venous thrombosis occurring more than one month before the start of study medication)
  13. Previous major surgical procedure, significant traumatic injury, or radiotherapy within the 4 weeks before inclusion
  14. Uncontrolled hypertension (systolic blood pressure >140 mmHg or diastolic pressure >90 mmHg) despite optimal medical management. Congestive heart failure: New York Heart Association (NYHA) ≥ class 2
  15. Unstable angina (angina symptoms at rest), new-onset angina (that started within the last 3 months)
  16. Myocardial infarction less than 6 months before starting the study treatment
  17. Uncontrolled cardiac arrhythmias
  18. History of epileptic seizures requiring long-term anticonvulsant therapy
  19. History of organ transplantation with use of immunosuppression therapy
  20. Ongoing bacterial or fungal infection (grade >2 by NCI-CTCAE v.5.0)
  21. Known history of human immunodeficiency virus (HIV) infection
  22. Active hepatitis B or C, or chronic hepatitis B or C requiring treatment with antiviral therapy
  23. Use of CYP3A4 inducers or inhibitors
  24. Pregnant or breast-feeding women
  25. Bowel malabsorption or extended bowel resection that could affect the absorption of regorafenib, occlusive syndrome, inability to take oral medications
  26. Inflammatory bowel disease with chronic diarrhoea
  27. Participation in another clinical trial within the 30 days before inclusion
  28. Concurrent treatment with another investigational product or anticancer therapy (other than irinotecan or regorafenib)
  29. Concomitant treatment with hypericum or live attenuated vaccines
  30. Gastro-intestinal fistula or perforation
  31. Person kept in detention or incapable of giving consent
  32. Patient unwilling or unable to comply with the medical follow-up required by the study because of geographic, social, or psychological reasons

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Regorafenib and Irinotecan
Irinotecan 180 mg/m² on Day1 and Day 15 of a 4 week cycle combined with regorafenib 160 mg daily on Day2-8 and D16-22 of a 4 week cycle administered until progression of disease or unacceptable toxicity.
Combination product: Regorafenib and Irinotecan
Irinotecan (180 mg/m² on D1 and D15 of a 4-week cycle) combined with regorafenib (160 mg daily on D2-8 and D16-22 of a 4-week cycle) administered until progression of disease or unacceptable toxicity
Other Names:
  • STIVARGA
  • CAMPTO
Active Comparator: Irinotecan
Irinotecan 180 mg/m² on Day1 and Day 15 of a 4 week cycle administered until progression of disease or unacceptable toxicity
Drug: Irinotecan
Irinotecan (180 mg/m² on D1 and D15 of a 4-week cycle) administered until progression of disease or unacceptable toxicity
Other Names:
  • CAMPTO

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
To compare the efficacy of regorafenib combined with irinotecan versus irinotecan alone in terms of overall survival (OS)
Time Frame: expected duration of 10 months from randomisation
Time duration from randomisation to time of death of any cause. If a patient is alive at the database cut-off date, then the patient will be censored at the last date of follow-up.
expected duration of 10 months from randomisation

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
To compare the efficacy of regorafenib combined with irinotecan versus irinotecan alone in terms of the overall survival rate
Time Frame: 6 and 12 months from randomisation
Overall survival rates at 6 and 12 months
6 and 12 months from randomisation
To compare the efficacy of regorafenib combined with irinotecan versus irinotecan alone in terms of the progression-free survival (PFS)
Time Frame: expected duration of 6 months from randomisation
Time duration from randomisation to time of first event (locoregional or distant relapse or progression, second malignancy, death from any cause).
expected duration of 6 months from randomisation
To evaluate the efficacy of regorafenib combined with irinotecan versus irinotecan alone in terms of the progression-free survival rate
Time Frame: 6 and 12 months from randomisation
Progression-free survival rates at 6 and 12 months
6 and 12 months from randomisation
To evaluate the efficacy of regorafenib combined with irinotecan versus irinotecan alone in terms of the disease control rate (DCR)
Time Frame: expected duration of 6 months from randomisation
Percentage of patients with complete response, partial response or stable disease as best response at the database cut-off date
expected duration of 6 months from randomisation
To evaluate the efficacy of regorafenib combined with irinotecan versus irinotecan alone in terms of the objective response rate (ORR)
Time Frame: expected duration of 6 months from randomisation
Percentage of patients with complete response or partial response
expected duration of 6 months from randomisation
To compare treatment-related toxicity
Time Frame: expected 30 days after last study treatment administration
Frequency and severity of adverse events assessed by NCI-CTCAE v5.0
expected 30 days after last study treatment administration
To compare the effect of treatment on quality of life
Time Frame: expected 30 days after last study treatment administration
Evaluation of quality of life with EORTC quality of life questionnaire for cancer patients (QLQ-C30)
expected 30 days after last study treatment administration
To compare the effect of treatment on quality of life related to gastro-oesophageal cancer
Time Frame: expected 30 days after last study treatment administration
Evaluation of quality of life with EORTC quality of life specific questionnaire for gastro-oesophageal tumours (QLQ-OG25)
expected 30 days after last study treatment administration

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
UNICANCER

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Bayer

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Emmanuelle SAMALIN-SCALZI, MD, Institut Du Cancer Montpellier

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 7, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 19, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 19, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 25, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 25, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 26, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 16, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 13, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • UC-0110/1807
  • 2018-002374-46 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Individual Participant Data will not be shared at an individual level, they will be part of the study database including all enrolled patients

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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