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Adenocarcinoma of the StomachPhase 1/2REGIRINCT03722108

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

A Phase 1/2 study testing Regorafenib and Irinotecan and Irinotecan in people with Adenocarcinoma of the Stomach and Adenocarcinoma of the Gastroesophageal Junction, run by UNICANCER at 27 sites in France.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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

Who is it for?
Ages 18 years and older
What is being tested?
Regorafenib and Irinotecan and Irinotecan
Could I receive a placebo?
No, everyone receives an active treatment
How many people
89 participants
Where
27 sitesFrance
Study dates
7 Feb 2019to 19 May 2022
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patient must have signed a written informed consent form prior to any study specific procedures
  • Patients aged ≥18 years old
  • Histologically confirmed diagnosis of gastro-oesophageal adenocarcinomas: gastroesophageal junction (Siewert II and III) and gastric adenocarcinomas
  • Asymptomatic primary tumour
  • Metastatic disease
  • At least one target lesion (according to RECIST v1.1):
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  • Unidimensionally measurable on cross-sectional imaging
  • In an area not previously irradiated
  • 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.
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤1
  • Life expectancy >3 months
  • Amylase ≤1.5 x upper limit of normal (ULN) and lipase ≤1.5 x ULN
  • 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)
  • 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
  • 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
  • Creatinine clearance (CLcr) ≥50 mL/min estimated by Cockcroft-Gault equation
  • 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
  • Patients affiliated to the social security system

Who cannot join

  • Symptomatic brain metastases or carcinomatous meningitis
  • Bone-only metastasis
  • Known and documented UGT1A1 deficiency
  • History of Gilbert's syndrome
  • 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)
  • 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)
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  • Interstitial lung disease with ongoing signs and symptoms at inclusion
  • Known hypersensitivity to any of the study drugs, study drug classes, or excipients
  • Non-healing wound, non-healing ulcer, or non-healing bone fracture
  • Patients with evidence or history of any bleeding diathesis, irrespective of severity
  • Any haemorrhage or bleeding event grade ≥3 (NCI-CTCAE v.5.0) within 4 weeks before starting of the study treatment
  • 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)
  • Previous major surgical procedure, significant traumatic injury, or radiotherapy within the 4 weeks before inclusion
  • 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
  • Unstable angina (angina symptoms at rest), new-onset angina (that started within the last 3 months)
  • Myocardial infarction less than 6 months before starting the study treatment
  • Uncontrolled cardiac arrhythmias
  • History of epileptic seizures requiring long-term anticonvulsant therapy
  • History of organ transplantation with use of immunosuppression therapy
  • Ongoing bacterial or fungal infection (grade >2 by NCI-CTCAE v.5.0)
  • Known history of human immunodeficiency virus (HIV) infection
  • Active hepatitis B or C, or chronic hepatitis B or C requiring treatment with antiviral therapy
  • Use of CYP3A4 inducers or inhibitors
  • Pregnant or breast-feeding women
  • Bowel malabsorption or extended bowel resection that could affect the absorption of regorafenib, occlusive syndrome, inability to take oral medications
  • Inflammatory bowel disease with chronic diarrhoea
  • Participation in another clinical trial within the 30 days before inclusion
  • Concurrent treatment with another investigational product or anticancer therapy (other than irinotecan or regorafenib)
  • Concomitant treatment with hypericum or live attenuated vaccines
  • Gastro-intestinal fistula or perforation
  • Person kept in detention or incapable of giving consent
  • Patient unwilling or unable to comply with the medical follow-up required by the study because of geographic, social, or psychological reasons

Trial locations and contacts

27 sites in 1 country.

27 sites in 1 country

France27 sites

  • Institut de Cancérologie de l'Ouest-Paul Papin

    Angers

  • Hôpital Morvan

    Brest

  • Clinique de Flandre

    Coudekerque-Branche

  • Centre Georges François Leclerc

    Dijon, 21079

  • Hôpital Franco-Britannique

    Levallois-Perret

  • Hopital Claude Huriez - CHU Lille

    Lille

  • CHU Dupuytren

    Limoges

  • Centre Léon Bérard

    Lyon

  • Hopital de la Timone

    Marseille

  • Institut Paoli Calmette

    Marseille

  • Institut du Cancer Montpellier

    Montpellier, 34298

  • Centre de Cancérologie du Grand Montpellier

    Montpellier

  • Centre Antoine Lacassagne

    Nice, 06189

  • Hopital Europeen Georges Pompidou

    Paris, 75015

  • GH Diaconesses Croix Saint-Simon

    Paris

  • CH Saint Jean

    Perpignan

  • CHU de Poitiers

    Poitiers, 86000

  • CH Annecy Genevois

    Pringy

  • Institut Jean Godinot

    Reims, 51100

  • Hopital Robert Debre

    Reims

  • Hopital Charles Nicolle

    Rouen

  • CHP Saint Grégoire

    Saint-Grégoire

  • Institut de Cancérologie de l'Ouest-René Gauducheau

    Saint-Herblain

  • CH Saint Malo

    St-Malo

  • Centre Paul Strass

    Strasbourg

  • CHRU Tours

    Tours

  • CHU Nancy - Hôpital Brabois

    Vandœuvre-lès-Nancy, 54500

Other trials in France

About this study

Official title: 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.

Read the 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.

Being tested
Regorafenib and Irinotecan, Irinotecan
Keywords
adenocarcinoma, gastro-oesophageal, regorafenib
Medical subject headings
Adenocarcinoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Regorafenib and IrinotecanCombination product

    Also called STIVARGA, CAMPTO

    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

  • IrinotecanDrug

    Also called CAMPTO

    Irinotecan (180 mg/m² on D1 and D15 of a 4-week cycle) administered until progression of disease or unacceptable toxicity

Study groups in NCT03722108
Study groupRoleWhat they receive
Regorafenib and IrinotecanExperimentalIrinotecan 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.
Receives: Combination Product: Regorafenib and Irinotecan
IrinotecanActive comparatorIrinotecan 180 mg/m² on Day1 and Day 15 of a 4 week cycle administered until progression of disease or unacceptable toxicity
Receives: Drug: Irinotecan

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. To compare the efficacy of regorafenib combined with irinotecan versus irinotecan alone in terms of overall survival (OS)

    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.

    Measured: expected duration of 10 months from randomisation

Secondary outcomes (8)

  1. To compare the efficacy of regorafenib combined with irinotecan versus irinotecan alone in terms of the overall survival rate

    Overall survival rates at 6 and 12 months

    Measured: 6 and 12 months from randomisation

  2. To compare the efficacy of regorafenib combined with irinotecan versus irinotecan alone in terms of the progression-free survival (PFS)

    Time duration from randomisation to time of first event (locoregional or distant relapse or progression, second malignancy, death from any cause).

    Measured: expected duration of 6 months from randomisation

  3. To evaluate the efficacy of regorafenib combined with irinotecan versus irinotecan alone in terms of the progression-free survival rate

    Progression-free survival rates at 6 and 12 months

    Measured: 6 and 12 months from randomisation

  4. To evaluate the efficacy of regorafenib combined with irinotecan versus irinotecan alone in terms of the disease control rate (DCR)

    Percentage of patients with complete response, partial response or stable disease as best response at the database cut-off date

    Measured: expected duration of 6 months from randomisation

  5. To evaluate the efficacy of regorafenib combined with irinotecan versus irinotecan alone in terms of the objective response rate (ORR)

    Percentage of patients with complete response or partial response

    Measured: expected duration of 6 months from randomisation

  6. To compare treatment-related toxicity

    Frequency and severity of adverse events assessed by NCI-CTCAE v5.0

    Measured: expected 30 days after last study treatment administration

  7. To compare the effect of treatment on quality of life

    Evaluation of quality of life with EORTC quality of life questionnaire for cancer patients (QLQ-C30)

    Measured: expected 30 days after last study treatment administration

  8. To compare the effect of treatment on quality of life related to gastro-oesophageal cancer

    Evaluation of quality of life with EORTC quality of life specific questionnaire for gastro-oesophageal tumours (QLQ-OG25)

    Measured: expected 30 days after last study treatment administration

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Oct 2018
  2. Study start7 Feb 2019
  3. Primary completion19 May 2022
  4. Study completion19 May 2022

Why it stopped: Unfavorable benefit-risk balance in the experimental arm following the IDMC for intermediate efficacy and safety analysis

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
89 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03722108
Sponsor's protocol ID
UC-0110/1807
Other IDs
2018-002374-46, 2018
Acronym
REGIRI
Status last verified
Oct 2023
First submitted
25 Oct 2018
Last updated
16 Oct 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: Individual Participant Data will not be shared at an individual level, they will be part of the study database including all enrolled patients

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Regorafenib and Irinotecan and Irinotecan in people with Adenocarcinoma of the Stomach and Adenocarcinoma of the Gastroesophageal Junction, run by UNICANCER at 27 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 16 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 27 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Unfavorable benefit-risk balance in the experimental arm following the IDMC for intermediate efficacy and safety analysis). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03722108.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2023.

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