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

Adenocarcinoma of the Gastroesophageal Junction Clinical Trial

— REGIRI  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03722108
• Other study ID #: UC-0110/1807
• Secondary ID: 2018-002374-46
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: February 7, 2019
• Est. completion date: May 19, 2022

Study information

• Verified date: October 2023
• Source: UNICANCER
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 89
• Est. completion date: May 19, 2022
• Est. primary completion date: May 19, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Adenocarcinoma
• Adenocarcinoma of the Gastroesophageal Junction
• Adenocarcinoma of the Stomach

Intervention

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

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

Locations

Country	Name	City	State
France	Institut de Cancérologie de l'Ouest-Paul Papin	Angers
France	Hôpital Morvan	Brest
France	Clinique de Flandre	Coudekerque-Branche
France	Centre Georges François Leclerc	Dijon
France	Hôpital Franco-Britannique	Levallois-Perret
France	Hopital Claude Huriez - CHU Lille	Lille
France	CHU Dupuytren	Limoges
France	Centre Léon Bérard	Lyon
France	Hopital de la Timone	Marseille
France	Institut Paoli Calmette	Marseille
France	Centre de Cancérologie du Grand Montpellier	Montpellier
France	Institut du Cancer Montpellier	Montpellier
France	Centre Antoine Lacassagne	Nice
France	GH Diaconesses Croix Saint-Simon	Paris
France	Hopital Europeen Georges Pompidou	Paris
France	CH Saint Jean	Perpignan
France	CHU de Poitiers	Poitiers
France	CH Annecy Genevois	Pringy
France	Hopital Robert Debre	Reims
France	Institut Jean Godinot	Reims
France	Hopital Charles Nicolle	Rouen
France	CHP Saint Grégoire	Saint-Grégoire
France	Institut de Cancérologie de l'Ouest-René Gauducheau	Saint-Herblain
France	CH Saint Malo	Saint-Malo
France	Centre Paul Strass	Strasbourg
France	CHRU Tours	Tours
France	CHU Nancy - Hôpital Brabois	Vandœuvre-lès-Nancy

Sponsors (2)

Lead Sponsor	Collaborator
UNICANCER	Bayer

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	expected duration of 10 months from randomisation
Secondary	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	6 and 12 months from randomisation
Secondary	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).	expected duration of 6 months from randomisation
Secondary	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	6 and 12 months from randomisation
Secondary	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	expected duration of 6 months from randomisation
Secondary	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	expected duration of 6 months from randomisation
Secondary	To compare treatment-related toxicity	Frequency and severity of adverse events assessed by NCI-CTCAE v5.0	expected 30 days after last study treatment administration
Secondary	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)	expected 30 days after last study treatment administration
Secondary	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)	expected 30 days after last study treatment administration