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

• Status: Active, not recruiting
• Trial end date: 2023-11-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: UNICANCER
• Treatments: Camptothecin; Irinotecan

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