Clinical Trial Results:
An Open-label Phase II Clinical trial of Panitumumab in Combination with Irinotecan for Patients with Advanced Metastatic Colorectal Cancer without KRAS mutation (Wild type) in third line chemotherapy (Patients pretreated with FOLFOX or XELOX ± bevacizumab and irinotecan alone or FOLFIRI or CAPIRI ± bevacizumab)
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Summary
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EudraCT number |
2007-004806-28 |
Trial protocol |
FR |
Global end of trial date |
30 Jun 2012
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Results information
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Results version number |
v1(current) |
This version publication date |
23 Jul 2016
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First version publication date |
23 Jul 2016
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
C07-1
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00655499 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
GERCOR
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Sponsor organisation address |
151 rue du faubourg saint Antoine , PARIS, France, 75011
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Public contact |
Regulatory affairs, GERCOR, 33 1 40 29 85 00, regulatory.affairs@gercor.com.fr
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Scientific contact |
coordinating investigator, Pr Thierry ANDRE, 33 1 40 29 85 00, regulatory.affairs@gercor.com.fr
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
06 Mar 2012
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
06 Feb 2012
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Global end of trial reached? |
Yes
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Global end of trial date |
30 Jun 2012
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To assess the objective response rate (ORR) when panitumumab is administered in combination with irinotecan for Patients with Advanced Metastatic Colorectal Cancer without KRAS mutation (Wild type) in third line chemotherapy = Patients pretreated with oxaliplatin and Fluorpyrimidines (5FU/FA or capecitabine) ± bevacizumab and Irinotecan alone or in association with Fluorpyrimidines (5FU/FA or capecitabine) ± bevacizumab
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Protection of trial subjects |
Pre-medication is not required for routine panitumumab infusions. If, during or after any infusion, a reaction occurs, pre-medication may be used for subsequent panitumumab infusions (e.g. acetaminophen/paracetamol and/or a histamine H1 antagonist, e.g. diphenhydramine).
Prior to the administration of irinotecan, all subjects should receive antiemetics agents (e.g.: oral or IV dexamethasone, 5-hydroxtryptamine3 (5-HT3) receptor antagonists). Antiemetic agents should be given on the day of treatment, starting at least 30 minutes prior to administration of irinotecan. Alternative and additional antiemetics may be used, where clinically indicated, at the discretion of the investigator or according to standard institutional or regional practice. In case of cholinergic like syndrome after irinotecan administration, atropine sulphate injection is recommended.
In case of toxicities, panitumumab and irinoteacan may need to be withheld, reducted and delayed.
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Background therapy |
- | ||
Evidence for comparator |
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Actual start date of recruitment |
16 Jul 2008
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
France: 69
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Worldwide total number of subjects |
69
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EEA total number of subjects |
69
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
36
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From 65 to 84 years |
33
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85 years and over |
0
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Recruitment
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Recruitment details |
From July 2008 to Oct. 2010, 69 patients were enrolled in the study, 4 were not eligible. The study was conducted in France, in 11 active centers: CH Haut Lévêque Pessac, CH Beauvais, CHI Montfermeil, CHU Pitié salpêtrière, St Antoine et Bichat Paris, Centre Paul Papin Angers, Clinique V. Hugo Le Mans, Hop. Foch Suresnes, Jean Mermoz Lyon, CHSenlis | ||||||
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Pre-assignment
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Screening details |
Patient wih pathologically confirmed mCRC, KRAS codon 12 and 13 wild type, previsously treated with irinotecan, oxaliplatin, fluoropyrimidines and bevacizumab. Eligibility criteria also included : age ≥ 18 years, normal hematopoietic , hepatic and renal fonctions, measurable disease.No prior treatment with anti-EGFR antibodies. | ||||||
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Period 1
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Period 1 title |
Overall Period
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Is this the baseline period? |
Yes | ||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||
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Arms
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Arm title
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Panitumumab combined with Irinotecan | ||||||
Arm description |
1cycle every 14 days (J1=J15) | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Panitumumab
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Investigational medicinal product code |
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Other name |
VECTIBIX
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Panitumumab : 6mg/kg in IV infusion over 60 minute on day 1
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Investigational medicinal product name |
Irinotecan
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Investigational medicinal product code |
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Other name |
CPT11
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Irinotecan: 180mg/m² in IV infusion over 90 minutes on day 1 just after panitumumab administration
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| Notes [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: 69 patients enrolled in the study and 4 non eligible (2 prior anti-EGFR antibodies (mab); 1 non prior irinotecan; 1 patient received bevacizumab in combination with study drug) |
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Baseline characteristics reporting groups
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Reporting group title |
Overall Period
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Reporting group description |
69 patients enrolled in the study and 4 non eligible (2 prior anti-EGFR antibodies (mab); 1 non prior irinotecan; 1 patient received bevacizumab in combination with study drug) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Panitumumab combined with Irinotecan
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Reporting group description |
1cycle every 14 days (J1=J15) | ||
Subject analysis set title |
Confirmed wild-type KRAS population
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
54 patients with wild-type KRAS confirmed at central assessment.
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Subject analysis set title |
All Wild-type population
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
41 patients with no mutations : "all wild" after central assessment
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Subject analysis set title |
Patients with KRAS, NRAS or BRAF mutation
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
19 patients with KRAS, NRAS and BRAF mutation after central assessment
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End point title |
Objective response rate (ORR) of the combination in KRAS WT mCRC patients [1] | ||||||||||||||||||||
End point description |
Incidence of either a radiologically confirmed CR or PR while in the combination treatment phase; subjects prematurely discontinuing without a post baseline tumour response assessment, or subjects who respond during the optional panitumumab monotherapy phase, or subjects with an observed CR or PR in the combination phase that is not confirmed (in either the combination
or monotherapy phases) will be considered non-responders.
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End point type |
Primary
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End point timeframe |
Data from the combination therapy phase alone, defined as the period from enrolment through to the decision to end irinotecan
Up to radiologically confirmed CR or PR while in the combination treatment phase
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The trial is descriptive with endpoints reported using counts, percents, conifdence interval and graphical methods. |
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
Disease control rate (DCR) | ||||||||||||||||||||
End point description |
Incidence of either a confirmed complete or partial response, or stable disease (SD) while in the combination therapy treatment phase; subjects prematurely discontinuing without a post-baseline tumour response assessment or subjects who have progressed by the first tumour response during the combination phase, or subjects with an observed complete or partial response in the combination phase that is not confirmed (in either the combination or monotherapy phases) will be considered non-responders otherwise.
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End point type |
Secondary
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End point timeframe |
A confirmed complete or partial response, or stable disease (SD) while in the combination therapy treatment phase
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
Progression-free survival (PFS) | ||||||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
The time from enrolment date to date of first radiologically observed progression or death (whichever comes first) combination therapy phase.
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| No statistical analyses for this end point | |||||||||||||||||||||
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End point title |
Overall survival (OS) | ||||||||||||||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
From the date of inclusion to the date of patient death, due to any cause, or to the last date the patient was known to be alive
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| No statistical analyses for this end point | |||||||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
From date of inclusion to 56 ± 3 days after the last dosing of study treatment
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
15.1
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Reporting groups
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Reporting group title |
Eligible study population
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Reporting group description |
1cycles every 14 days (J1=J15) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 1% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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04 Aug 2008 |
Suppression of windows scheduled dose. Panitumumab and irinotecan can be administrated as soon as possible.
Modification of intra dermal dose injection (ancillary study) |
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21 Jan 2009 |
The determination of Kras status could be performed locally, where the investigator usually requires such test. Nevertheless the wild type KRAS status will be confirmed by sending tumour block to the European Hospital Georges Pompidou following the enrolment step. |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
