Valproic Acid in Combination With Bevacizumab and Oxaliplatin/Fluoropyrimidine Regimens in Patients With Ras-mutated Metastatic Colorectal Cancer
- Conditions
- Ras-mutated Metastatic Colorectal Cancer
- Interventions
- Drug: mFOLFOX6 regimenDrug: mOXXEL regimen
- Registration Number
- NCT04310176
- Lead Sponsor
- National Cancer Institute, Naples
- Brief Summary
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.
- Detailed Description
Patients will be randomized 1:1 to receive oxaliplatin based chemotherapy (mFOLFOX6/mOXELL) plus bevacizumab for 12 cycles or the same chemotherapy plus bevacizumab and valproic acid for 12 cycle.
Thereafter, in both arms, patients who are progression free after 12 cycles (24 weeks) of treatment continue maintenance bevacizumab+fluoropyrimidines until disease progression or unacceptable toxicity.
Surgery may be carried out in case of appropriate tumour reduction is evident at response evaluation. Resectability has to be evaluated by a multidisciplinary review team and the decision regarding post-surgery chemotherapy is at the discretion of the investigators, according to the policy commonly adopted by their Institution in clinical practice.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 200
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Standard mFOLFOX6 regimen Chemotherapy (mFOLFOX-6/mOXELL) + Bevacizumab for 12 cycles (24 weeks) Maintenance treatment (Standard): Fluoropyrimidines (5-Fluorouracil/Capecitabine) + Bevacizumab until disease progression or unacceptable toxicity Standard mOXXEL regimen 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 mFOLFOX6 regimen 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 Experimental mOXXEL regimen 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 Experimental Valproic acid 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 Experimental Capecitabine 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 Experimental 5-fluorouracil 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 Standard Bevacizumab Chemotherapy (mFOLFOX-6/mOXELL) + Bevacizumab for 12 cycles (24 weeks) Maintenance treatment (Standard): Fluoropyrimidines (5-Fluorouracil/Capecitabine) + Bevacizumab until disease progression or unacceptable toxicity Standard 5-fluorouracil Chemotherapy (mFOLFOX-6/mOXELL) + Bevacizumab for 12 cycles (24 weeks) Maintenance treatment (Standard): Fluoropyrimidines (5-Fluorouracil/Capecitabine) + Bevacizumab until disease progression or unacceptable toxicity Standard Capecitabine 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 Bevacizumab 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 Measures
Name Time Method progression-free survival (PFS) until progression of disease (up to 5 years) PFS is defined as the time elapsed from the date of randomization to the date of progression, as defined by investigators, or the date of death, whichever comes first
- Secondary Outcome Measures
Name Time Method overall survival (OS) 5 years OS is defined as the time elapsed from randomization to death due to any cause
centrally reviewed PFS (CR-PFS) at week 12th and 24th and thereafter every 12 weeks until progression of disease (up to 5 years( FSCR is also measured as the time elapsed from the date of randomization to the date of progression, as defined by independent blind central review, or the date of death, whichever comes first
Determination of changes in quality of life at baseline, at week 12th and 24th and every 12 weeks thereafter until progression disease (up to 5 years) EORTC QLQ-C30, a quality of life questionnaires, composed by 30 items graded from1 (not at all) to 4 (very much) after 1 year from the diagnosis
Number of participants with treatment-related side effects baseline, day 1 of each cycle and on maintenance treatment until progression disease (up to 5 years) graded according to Common Criteria for Adverse Events (CTCAE) version 5.0
metastases resection rate (R0/R1/R2) up to 24 weeks determined at surgery (resection status) by pathologist follow: R0 no cancer cells at the resection margin; R1 microscopic positive margin, R2 macroscopic positive margin
Response rate at week 12th and 24th and thereafter every 12 weeks until progression of disease (up to 5 years) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Trial Locations
- Locations (1)
Istituto Tumori di Napoli - Fondazione G. Pascale
🇮🇹Napoli, Campania, Italy