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

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ClinicalTrials.gov Identifier: NCT03722108
Recruitment Status : Terminated (Unfavorable benefit-risk balance in the experimental arm following the IDMC for intermediate efficacy and safety analysis)
First Posted : October 26, 2018
Last Update Posted : July 29, 2022
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
UNICANCER

Study Description
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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
Adenocarcinoma of the Stomach Adenocarcinoma of the Gastroesophageal Junction Combination Product: Regorafenib and Irinotecan Drug: Irinotecan 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
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Study Type : Interventional  (Clinical Trial)
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 : February 7, 2019
Actual Primary Completion Date : May 19, 2022
Actual Study Completion Date : May 19, 2022

Resource links provided by the National Library of Medicine


Arms and Interventions
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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 Name: CAMPTO


Outcome Measures
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Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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

  2. 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).

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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)

  8. 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)


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03722108


Locations
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Sponsors and Collaborators
UNICANCER
Bayer
Investigators
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Principal Investigator: Emmanuelle SAMALIN-SCALZI, MD Institut du Cancer Montpellier
More Information
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Responsible Party: UNICANCER
ClinicalTrials.gov Identifier: NCT03722108    
Other Study ID Numbers: UC-0110/1807
2018-002374-46 ( EudraCT Number )
First Posted: October 26, 2018    Key Record Dates
Last Update Posted: July 29, 2022
Last Verified: July 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
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

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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:
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Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Irinotecan
 Topoisomerase I Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents