Histopathological Response to FOLFOXIRI + Bevacizumab in Peritoneal Metastasis From Colorectal Cancer

• Status: Unknown status
• Trial end date: 2020-02-01
• Target enrollment: 0
• Participant gender: All

Summary

There is a paucity of data on the histopathological response of peritoneal tumor deposits from colorectal cancer to neoadjuvant chemotherapy. Particularly, no prospective assessment of chemotherapy-associated histopathological response within the peritoneum has been performed so far. Therefore, there is an urgent need to conduct a clinical trial aimed at prospectively assessing the histopathological response within the peritoneum in patients with peritoneal metastasis from colorectal cancer.

Recently, Loupakis et al. reported that the triplet regimen of 5-fluorouracil, oxaliplatin and irinotecan (FOLFOXIRI) in combination with bevacizumab significantly improved median progression-free survival in metastatic colorectal cancer patients from 9.7 to 12.1 months as compared with fluorouracil, leucovorin, and irinotecan (FOLFIRI) + bevacizumab. In view of these data, it is likely that FOLFOXIRI + bevacizumab will also lead to a significant improvement of the histopathological response within the peritoneum of patients with peritoneal metastasis from colorectal cancer (pcCRC) as compared with previous standard chemotherapy.

The investigators hypothesize that FOLFOXIRI + bevacizumab will induce a pCR or major response in peritoneal tumor deposits in >30% of patients (taking the response rate to FOLFOX- or FOLFIRI-based neoadjuvant chemotherapy from the published literature as a reference).

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

Details

• Lead Sponsor: Medical University of Vienna
• Treatments: Bevacizumab; Fluorouracil; Irinotecan; Oxaliplatin

Criteria

Inclusion Criteria:

1. Histologically confirmed carcinoma of the colon or rectum with synchronous or metachronous peritoneal metastasis.

2. Male and female patients, aged ≥ 18 years.

3. Eastern Cooperative Oncology Group (ECOG) performance score of ≤ 2.

4. Life expectancy ≥ 26 weeks.

5. Neutrophils (absolute count) ≥ 1.5 g/l.

6. Platelet count ≥ 100 g/l.

7. Hemoglobin > 9 g/dL.

8. Total bilirubin ≤ 1.8 mg/dl.

9. Aspartate aminotransferase (AST) and Alanine transaminase (ALT) ≤ 88 U/l (≤ 175 U/l if liver metastases are present).

10. Alkaline phosphatase ≤ 325 U/l (≤ 650 U/l if liver metastases are present).

11. Calculated creatinine clearance > 50 mL/min OR serum creatinine ≤ 1.5 mg/dl.

12. Proteinuria < 2+ by dipstick or urine protein <1 g by 24-hr urine collection.

13. Not pregnant or nursing.

14. Negative pregnancy test (for females of childbearing potential).

15. Patients of childbearing / reproductive potential should use adequate birth control measures, as defined by the investigator, during the study treatment period and for at least 6 months after the last study treatment.

16. Written informed consent.

17. General condition considered feasible for major abdominal surgery after systemic chemotherapy.

18. ≤3 liver metastases amenable to curative resection using a minor liver resection.

Exclusion Criteria:

1. Major surgical procedure or significant traumatic injury within 28 days prior to study enrolment (surgical exploration with diagnostic biopsy/sampling of peritoneal tumor deposits but without bowel resection or comparable surgical procedure is allowed).

2. History of previous cytoreductive surgery in combination with hyperthermic intraperitoneal chemotherapy.

3. Pregnancy or lactation.

4. Inability or unwillingness to comply with the protocol.

5. Evidence of current extraabdominal metastatic disease. Prior extraabdominal metastatic disease is allowed, provided that it has been curatively resected ≥6 months before study entry and that current staging shows no evidence of disease recurrence.

6. >3 liver metastases or any liver metastases not amenable to upfront curative resection using a minor liver resection.

7. Prior systemic chemotherapy completed ≤3 months before study inclusion.

8. Treatment with any other investigational agent, or participation in another clinical trial within 30 days prior to entering this study.

9. History or evidence upon physical/neurological examination of central nervous system (CNS) disease (unrelated to cancer) unless adequately treated with standard medical therapy (e.g. uncontrolled seizures).

10. Untreated brain metastases, spinal cord compression or primary brain tumors.

11. Past or current history (within the last 2 years prior to treatment start) of other malignancies except colorectal cancer (patients with curatively treated basal and squamous cell carcinoma of the skin or in situ carcinoma of the cervix are eligible).

12. Clinically significant cardiovascular disease, for example cerebrovascular accident (CVA), myocardial infarction (≤12 months before treatment start), unstable angina, New York Heart Association (NYHA) > Class II congestive heart failure (CHF), arrhythmia requiring medication, or uncontrolled hypertension.

13. Significant vascular disease (e.g. aortic aneurysm requiring surgical repair or recent arterial thrombosis) within 6 months of study enrolment.

14. Any previous venous thromboembolism > NCI Common Toxicity Criteria for Adverse Effects (CTCAE) Grade 3.

15. Prior history of hypertensive crisis or hypertensive encephalopathy.

16. Evidence of bleeding diathesis or significant coagulopathy.

17. History of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess or active gastrointestinal bleeding within 6 months prior to the first study treatment.

18. Known hypersensitivity to any of the study drugs.

19. Serious, non-healing wound, ulcer or bone fracture.

20. Evidence of any other disease, metabolic dysfunction, physical examination finding or laboratory finding giving reasonable suspicion of a disease or condition that puts the patient at high risk for treatment-related complications.

21. Symptomatic peripheral neuropathy ≥ grade 1 according to the NCI Common Toxicity Criteria.