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

NCT ID: NCT03722108

Last Updated: 2023-10-16

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 89 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-02-07
• Study Completion Date: 2022-05-19

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.

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.

Conditions

Adenocarcinoma of the Stomach; Adenocarcinoma of the Gastroesophageal Junction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Regorafenib and Irinotecan

Intervention Type: COMBINATION_PRODUCT

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

Irinotecan

Irinotecan 180 mg/m² on Day1 and Day 15 of a 4 week cycle administered until progression of disease or unacceptable toxicity

Group Type: ACTIVE_COMPARATOR

Irinotecan

Intervention Type: DRUG

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

Interventions

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

Intervention Type: COMBINATION_PRODUCT

Irinotecan

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

Intervention Type: DRUG

Other Intervention Names

STIVARGA; CAMPTO; CAMPTO

Eligibility 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)

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bayer

INDUSTRY

Sponsor Role: collaborator

UNICANCER

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Emmanuelle SAMALIN-SCALZI, MD

Role: PRINCIPAL_INVESTIGATOR

Institut du Cancer Montpellier

Locations

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

Institut du Cancer Montpellier

Montpellier, , France

Centre de Cancérologie du Grand Montpellier

Montpellier, , France

Centre Antoine Lacassagne

Nice, , France

Hopital Europeen Georges Pompidou

Paris, , France

GH Diaconesses Croix Saint-Simon

Paris, , France

CH Saint Jean

Perpignan, , France

CHU de Poitiers

Poitiers, , France

CH Annecy Genevois

Pringy, , France

Institut Jean Godinot

Reims, , France

Hopital Robert Debre

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

St-Malo, , France

Centre Paul Strass

Strasbourg, , France

CHRU Tours

Tours, , France

CHU Nancy - Hôpital Brabois

Vandœuvre-lès-Nancy, , France

Countries

France

Other Identifiers

2018-002374-46

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

UC-0110/1807

Identifier Type: -

Identifier Source: org_study_id