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

Sponsor
UNICANCER (Other)
Overall Status
Terminated
CT.gov ID
NCT03722108
Collaborator
Bayer (Industry)
89
Enrollment
27
Locations
2
Arms
39.3
Actual Duration (Months)
3.3
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease Intervention/Treatment Phase
Phase 1/Phase 2

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 Design

Study Type:
Interventional
Actual Enrollment :
89 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Randomised Phase 2 Trial Assessing REGorafenib Combined With IRInotecan as Second-line Treatment in Patients With Metastatic Gastro-oesophageal Adenocarcinomas
Actual Study Start Date :
Feb 7, 2019
Actual Primary Completion Date :
May 19, 2022
Actual Study Completion Date :
May 19, 2022

Arms and Interventions

Arm Intervention/Treatment
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

    		•

    Outcome Measures

    Primary Outcome Measures

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

    Secondary Outcome Measures

    1. To compare the efficacy of regorafenib combined with irinotecan versus irinotecan alone in terms of the overall survival rate [6 and 12 months from randomisation]

      Overall survival rates at 6 and 12 months

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

    3. To evaluate the efficacy of regorafenib combined with irinotecan versus irinotecan alone in terms of the progression-free survival rate [6 and 12 months from randomisation]

      Progression-free survival rates at 6 and 12 months

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

    5. To evaluate the efficacy of regorafenib combined with irinotecan versus irinotecan alone in terms of the objective response rate (ORR) [expected duration of 6 months from randomisation]

      Percentage of patients with complete response or partial response

    6. To compare treatment-related toxicity [expected 30 days after last study treatment administration]

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

    7. To compare the effect of treatment on quality of life [expected 30 days after last study treatment administration]

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

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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    1. 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.

    2. Eastern Cooperative Oncology Group (ECOG) performance status ≤1

    3. Life expectancy >3 months

    4. Amylase ≤1.5 x upper limit of normal (ULN) and lipase ≤1.5 x ULN

    5. 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)

    1. 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

    2. 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

    3. Creatinine clearance (CLcr) ≥50 mL/min estimated by Cockcroft-Gault equation

    4. 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

    5. 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Institut de Cancérologie de l'Ouest-Paul Papin Angers France
    2 Hôpital Morvan Brest France
    3 Clinique de Flandre Coudekerque-Branche France
    4 Centre Georges François Leclerc Dijon France 21079
    5 Hôpital Franco-Britannique Levallois-Perret France
    6 Hopital Claude Huriez - CHU Lille Lille France
    7 CHU Dupuytren Limoges France
    8 Centre Léon Bérard Lyon France
    9 Hopital de la Timone Marseille France
    10 Institut Paoli Calmette Marseille France
    11 Institut du Cancer Montpellier Montpellier France 34298
    12 Centre de Cancérologie du Grand Montpellier Montpellier France
    13 Centre Antoine Lacassagne Nice France 06189
    14 Hopital Europeen Georges Pompidou Paris France 75015
    15 GH Diaconesses Croix Saint-Simon Paris France
    16 CH Saint Jean Perpignan France
    17 CHU de Poitiers Poitiers France 86000
    18 CH Annecy Genevois Pringy France
    19 Institut Jean Godinot Reims France 51100
    20 Hopital Robert Debre Reims France
    21 Hopital Charles Nicolle Rouen France
    22 CHP Saint Grégoire Saint-Grégoire France
    23 Institut de Cancérologie de l'Ouest-René Gauducheau Saint-Herblain France
    24 CH Saint Malo Saint-Malo France
    25 Centre Paul Strass Strasbourg France
    26 CHRU Tours Tours France
    27 CHU Nancy - Hôpital Brabois Vandœuvre-lès-Nancy France 54500

    Sponsors and Collaborators

    • UNICANCER
    • Bayer

    Investigators

    • Principal Investigator: Emmanuelle SAMALIN-SCALZI, MD, Institut du Cancer Montpellier

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    UNICANCER
    ClinicalTrials.gov Identifier:
    NCT03722108
    Other Study ID Numbers:
    • UC-0110/1807
    • 2018-002374-46
    First Posted:
    Oct 26, 2018
    Last Update Posted:
    Jul 29, 2022
    Last Verified:
    Jul 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by UNICANCER
    adenocarcinoma
    gastro-oesophageal
    regorafenib
    Additional relevant MeSH terms:
    Adenocarcinoma
    Irinotecan

    Study Results

    No Results Posted as of Jul 29, 2022