Ignite Creation Date:
2024-05-06 @ 2:47 PM
Last Modification Date:
2024-10-26 @ 1:37 PM
Study NCT ID:
NCT04425239
Status:
COMPLETED
Last Update Posted:
2022-04-07
First Post:
2020-05-03
Brief Title:
Intermittent or Continuous Panitumumab Plus FOLFIRI for RASB-RAF Wild-type Metastatic Colorectal Cancer
Sponsor:
National Cancer Institute Naples
Organization:
National Cancer Institute Naples
Study Overview
Official Title:
Intermittent or Continuous Panitumumab Plus FOLFIRI for First-line Treatment of Patients With RASB-RAF Wild-type Metastatic Colorectal Cancer a Randomized Phase 2 Trial
Status:
COMPLETED
Status Verified Date:
2021-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
IMPROVE
Brief Summary:
The investigators hypothesize that intermittent first-line Panitumumab plus FOLFIRI is effective as the same regimen given continuously in unresectable metastatic RAS and BRAF wild type colorectal cancer patients Correlative studies on tumor and blood samples could identify potential biomarkers of efficacy and help defining personalized treatment strategy
Detailed Description:
This will be a multicenter open label randomized phase II study The study population will include untreated RAS wild-type metastatic colorectal mCRC patients with unresectable disease A total of 136 patients will be enrolled
All Patients will receive an induction treatment with panitumumab as 1 hour intravenous infusion at the dosage of 6 mgkg given every two weeks plus FOLFIRI chemotherapy as standard guidelines
Before start of FOLFIRI plus panitumumab at the time of enrollment patients will be immediately randomized electronically 11 to one of the two arms Induction treatment with FOLFIRI plus panitumumab will continue until progressive disease unacceptable toxicity or informed consent withdrawal or for up to 8 cycles At the end of induction treatment in presence of complete or partial response or stable disease non-progressing patients will be allocated to one of the two pre-assigned arms
A CONTINOUS FOLFIRI plus panitumumab until progressive disease unacceptable toxicity or informed consent withdrawal Panitumumab will be administered as a 6 mgkg intravenous infusion over 60 minutes day 1 every 2 weeks The dose of Panitumumab should be administered prior to chemotherapy Irinotecan will be administered as a 180 mgm2 intravenous infusion over 60 minutes day 1 every 2 weeks Folinic acid will be administered as a 200 mgm2 intravenous infusion over 120 minutes before 5- fluorouracil infusion day 1 every 2 weeks 5-fluorouracil will be administered as a 400 mgm2 intravenous bolus injection day 1 followed by 2400 mgm246-hours continuous infusion day 1 every 2 weeks Cycle length will be 2 weeks - 3 days
B INTERMITTENT treatment free interval until progressive disease followed by up to 8 cycles of FOLFIRI plus panitumumab in presence of complete or partial response or stable disease non-progressing patients will undergo again to treatment free interval until PD when they will restart treatment Treatment cycling will continue till any progressive disease on treatment Panitumumab will be administered at same dose and infusion with FOLFIRI
All measurable and non-measurable lesions must be documented at screening within 21 days prior to randomization and re-assessed at each subsequent tumor evaluation every 8 weeks while the patient is on study Tumor assessment by CT scan of chest abdomen and pelvis CEA CA 199 and any other tests having resulted positive during baseline staging will be performed at week 8 and every 8 weeks thereafter until disease progression accordingly with RECIST V 11 criteria
Toxicities will be evaluated throughout the study treatment and graded according to the NCI Common Toxicity Criteria
The National Cancer Institute Common Toxicity Criteria for Adverse Events NCI CTC-AE Version 403 will be used to evaluate the clinical safety of the treatment in this study Patients will be assessed for AEs at each clinical visit and as necessary throughout the study
Quality of Life is assessed by the EORTC QLQ-C30 v 30 questionnaire that are completed by patients at baseline at week 16 and every 8 weeks thereafter
Biomarkers ancillary study Correlative biological studies will be performed for the evaluation of the biomarkers indicated above on the biological samples available paraffin-embedded tissue frozen tissue blood serum etc Biomarkers will be evaluated on archival tumor tissues or on newly obtained biopsies at baseline and during treatment when available Blood Samples will be collected at baseline at week 8 16 and thereafter every 8 weeks concomitantly with tumor assessment
The sample size is calculated on the basis of median progression-free survival on treatment with intermittent vs continuous Panitumumab plus FOLFIRI taking into account a median PFS of 11 months observed in the CRYSTAL trial
The study is designed as a phase II trial with a random assignment to a calibration arm continous and to the experimental arm intermittent The sample size for intermittent arm is calculated according to the binomial test The calibration arm has the same sample size its role is to give a parallel estimation of median PFS to ensure that sample is representative and results are consistent However considering a 5 of drop-outs mainly due to losses to follow-up the sample size is increased from 130 to 136 patients
Randomization will be performed with a minimization procedure that will account for center ECOG PS 0-1 vs 2 primary site of tumor Right versus Left adjuvant treatment yes vs no metastatic sites 1 vs1
All Patients will receive an induction treatment with panitumumab as 1 hour intravenous infusion at the dosage of 6 mgkg given every two weeks plus FOLFIRI chemotherapy as standard guidelines
Before start of FOLFIRI plus panitumumab at the time of enrollment patients will be immediately randomized electronically 11 to one of the two arms Induction treatment with FOLFIRI plus panitumumab will continue until progressive disease unacceptable toxicity or informed consent withdrawal or for up to 8 cycles At the end of induction treatment in presence of complete or partial response or stable disease non-progressing patients will be allocated to one of the two pre-assigned arms
A CONTINOUS FOLFIRI plus panitumumab until progressive disease unacceptable toxicity or informed consent withdrawal Panitumumab will be administered as a 6 mgkg intravenous infusion over 60 minutes day 1 every 2 weeks The dose of Panitumumab should be administered prior to chemotherapy Irinotecan will be administered as a 180 mgm2 intravenous infusion over 60 minutes day 1 every 2 weeks Folinic acid will be administered as a 200 mgm2 intravenous infusion over 120 minutes before 5- fluorouracil infusion day 1 every 2 weeks 5-fluorouracil will be administered as a 400 mgm2 intravenous bolus injection day 1 followed by 2400 mgm246-hours continuous infusion day 1 every 2 weeks Cycle length will be 2 weeks - 3 days
B INTERMITTENT treatment free interval until progressive disease followed by up to 8 cycles of FOLFIRI plus panitumumab in presence of complete or partial response or stable disease non-progressing patients will undergo again to treatment free interval until PD when they will restart treatment Treatment cycling will continue till any progressive disease on treatment Panitumumab will be administered at same dose and infusion with FOLFIRI
All measurable and non-measurable lesions must be documented at screening within 21 days prior to randomization and re-assessed at each subsequent tumor evaluation every 8 weeks while the patient is on study Tumor assessment by CT scan of chest abdomen and pelvis CEA CA 199 and any other tests having resulted positive during baseline staging will be performed at week 8 and every 8 weeks thereafter until disease progression accordingly with RECIST V 11 criteria
Toxicities will be evaluated throughout the study treatment and graded according to the NCI Common Toxicity Criteria
The National Cancer Institute Common Toxicity Criteria for Adverse Events NCI CTC-AE Version 403 will be used to evaluate the clinical safety of the treatment in this study Patients will be assessed for AEs at each clinical visit and as necessary throughout the study
Quality of Life is assessed by the EORTC QLQ-C30 v 30 questionnaire that are completed by patients at baseline at week 16 and every 8 weeks thereafter
Biomarkers ancillary study Correlative biological studies will be performed for the evaluation of the biomarkers indicated above on the biological samples available paraffin-embedded tissue frozen tissue blood serum etc Biomarkers will be evaluated on archival tumor tissues or on newly obtained biopsies at baseline and during treatment when available Blood Samples will be collected at baseline at week 8 16 and thereafter every 8 weeks concomitantly with tumor assessment
The sample size is calculated on the basis of median progression-free survival on treatment with intermittent vs continuous Panitumumab plus FOLFIRI taking into account a median PFS of 11 months observed in the CRYSTAL trial
The study is designed as a phase II trial with a random assignment to a calibration arm continous and to the experimental arm intermittent The sample size for intermittent arm is calculated according to the binomial test The calibration arm has the same sample size its role is to give a parallel estimation of median PFS to ensure that sample is representative and results are consistent However considering a 5 of drop-outs mainly due to losses to follow-up the sample size is increased from 130 to 136 patients
Randomization will be performed with a minimization procedure that will account for center ECOG PS 0-1 vs 2 primary site of tumor Right versus Left adjuvant treatment yes vs no metastatic sites 1 vs1
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None