Valproic Acid in Combination With Bevacizumab and Oxaliplatin/Fluoropyrimidine Regimens in Patients With Ras-mutated Metastatic Colorectal Cancer

Sponsor
National Cancer Institute, Naples
Study ID
NCT04310176
Phase
PHASE2
Status
Unknown

Conditions

  • Ras-mutated Metastatic Colorectal Cancer

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Bevacizumab — DRUG
    5 mg/m2 as 20-to-30 minute intravenous (i.v.) infusion every two weeks. Maintenance treatment (both arms): 5 mg/m2 every 2 weeks (in combination with 5-Fluorouracil) or 7.5 mg/m2 every 3 weeks (in combination with capecitabine)
  • mFOLFOX6 regimen — DRUG
    Oxaliplatin 85 mg/m2 as 2-3 hours i.v. infusion on day 1 followed by levo-folinic acid 200 mg/m2 as 1- 2 hours i.v. infusion followed by i.v bolus. 5-fluorouracil 400 mg/m2, and a 46-hour i.v. infusion of 5-fluorouracil 2400 mg/m2 every two week
  • mOXXEL regimen — DRUG
    Oxaliplatin 85 mg/m2 as 2-3 hours i.v. infusion on day 1 plus oral capecitabine 1000 mg/m2 twice daily on days 1 to 10, every 2 weeks
  • Valproic acid — DRUG
    given orally from 500mg-1500mg daily and an intra-patient titration for a target serum level of 50-100µg/ml
  • Capecitabine — DRUG
    Maintenance treatment (both arms): 1250 mg/m2 twice daily on days 1 to 14, every 3 weeks or 1250 mg/m2 twice daily on days 1 to 10, every 2 weeks
  • 5-fluorouracil — DRUG
    Maintenance treatment (both arms): Levo-folinic acid 200 mg/m2 as 1- 2 hours i.v. infusion followed by i.v bolus. 5-fluorouracil 400 mg/m2, and a 46-hour i.v. infusion of 5-fluorouracil 2400 mg/m2 every two weeks

Study Details

The primary aim of this study is to test whether the combination of valproic acid with bevacizumab and oxaliplatin/fluoropyrimidine regimens (mFOLFOX6/mOXXEL) can prolong progression free survival (PFS) as compared with bevacizumab and oxaliplatin/fluoropyrimidine regimens alone as first-line treatment in patients with metastatic colorectal cancer with mutation of RAS.

Key Dates

First listed
Mar 17, 2020
Start date
May 24, 2019
Status verified
Mar 2023
Primary completion
Dec 31, 2023
Completion
Nov 30, 2024

Study Design

Enrollment
200 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Active Comparator: Standard
    Chemotherapy (mFOLFOX-6/mOXELL) + Bevacizumab for 12 cycles (24 weeks) Maintenance treatment (Standard): Fluoropyrimidines (5-Fluorouracil/Capecitabine) + Bevacizumab until disease progression or unacceptable toxicity
  • Experimental: Experimental
    Chemotherapy (mFOLFOX-6/mOXELL) + Bevacizumab + Valproic Acid administered oral daily from day -14 increasing doses and an intra-patient titration for a target serum level of 50-100µg/ml for 12 cycles (24 weeks) Maintenance treatment (Experimental): Fluoropyrimidines (5-Fluorouracil/Capecitabine) + Bevacizumab + Valproic Acid until disease progression or unacceptable toxicity

Primary Outcome Measure

progression-free survival (PFS) [ Time Frame: until progression of disease (up to 5 years) ]

Central Contacts

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