Clinical Trial Results:
Phase II study of panitumumab as a first line agent in fragile elderly patients with advanced colorectal cancer with non-mutated KRAS
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Summary
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EudraCT number |
2009-016661-28 |
Trial protocol |
ES |
Global end of trial date |
31 Jul 2014
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Results information
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Results version number |
v1(current) |
This version publication date |
27 Mar 2019
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First version publication date |
27 Mar 2019
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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 |
TTD-09-03
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01126112 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Spanish Cooperative Group for the Treatment of Digestive Tumors (TTD)
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Sponsor organisation address |
C/ Téllez nº30 posterior, planta 1ª, oficina 4-2/4-3, Madrid, Spain, 28007
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Public contact |
Inmaculada Ruiz de Mena, Spanish Cooperative Group for the Treatment of Digestive Tumors (TTD), +34 913788275, ttd@ttdgroup.org
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Scientific contact |
Inmaculada Ruiz de Mena, Spanish Cooperative Group for the Treatment of Digestive Tumors (TTD), +34 913788275, ttd@ttdgroup.org
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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 |
31 Jul 2014
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
19 Sep 2013
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Global end of trial reached? |
Yes
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Global end of trial date |
31 Jul 2014
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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 estimate the 6-month progression-free survival (PFS) of frail elderly subjects treated with panitumumab as a first-line chemotherapy regimen in subjects with metastatic colorectal cancer (mCRC) with non-mutated KRAS.
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Protection of trial subjects |
Throughout the study, the researchers were able to prescribe any medication or concomitant treatment they considered necessary to provide adequate supportive assistance. Topical, oral or intravenous antibiotics were used to treat skin or nail-related toxicities at the discretion of the investigator. For the subjects with anticoagulant treatment, a strict control of the coagulation parameters was recommended during the treatment period of the study. For low white blood cell count, granulocyte colony stimulating factor (G-CSF) could be used; however in this trial the routine prophylactic use of G-CSF was not recommended. G-CSF for therapeutic purposes in patients with serious neutropenic complications such as tissue infections, sepsis, fungal infections, etc., could be administered at the discretion of the investigator or if it was the standard protocol in the institution. Regional variations were acceptable practice. The epoetins could be used according to the investigator's criteria to treat chemotherapy-induced anemia.
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Background therapy |
It is widely known that frail elderly patients with mCRC are not candidates for chemotherapy due to potential undesirable effects, including the possibility of toxic death, which exceeds the potential benefits in quality of life and survival. The anti-epidermal growth factor receptor (EGFR) monoclonal antibody, Panitumumab, has demonstrated efficacy and a manageable safety profile as a monotherapy and in combination with chemotherapy (as first- or second-line therapy), for the treatment of mCRC in patients with wild-type (WT) KRAS (exon 2) tumours. In addition, the toxicity profile is moderate when used in monotherapy; the main toxicity occurs in the skin. Finally, because of its pharmacokinetic profile, panitumumab can be administered every 2 weeks, which reduces hospital visits compared to the weekly schedule. Studies of the factors that predict efficacy have shown that patients with non-mutated KRAS can only benefit from an anti-EGFR treatment. | ||
Evidence for comparator |
Not applicable. | ||
Actual start date of recruitment |
21 Jul 2010
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Safety, Efficacy | ||
Long term follow-up duration |
30 Months | ||
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 |
Spain: 33
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Worldwide total number of subjects |
33
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EEA total number of subjects |
33
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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) |
0
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From 65 to 84 years |
28
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85 years and over |
5
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Recruitment
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Recruitment details |
33 patients were included: 22 males and 11 females. All patients were Caucasians. This was a national study with all patients being included at 14 Spanish sites. | ||||||
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Pre-assignment
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Screening details |
Key inclusion criteria: patients ≥70 years of age; patients with mCRC not prone for surgical resection; WT KRAS (exon 2); measurable disease according to the mRECIST criteria (version 1.1); ECOG status 6 3; magnesium levels ≥ the lower limit of normal. Intermediate or high risk prognostic factors according to KPC ineligible for chemotherapy. | ||||||
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Pre-assignment period milestones
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Number of subjects started |
33 | ||||||
Number of subjects completed |
33 | ||||||
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Period 1
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Period 1 title |
Baseline (overall period)
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Is this the baseline period? |
Yes | ||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||
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Arms
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Arm title
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Wild-type KRAS mCRC | ||||||
Arm description |
Wild-type KRAS mCRC patients. Panitumumab will be administered by intravenous (i.v.) infusion at a dose of 6 mg/kg once every 14 days until disease progression is diagnosed, at which time those subjects will be withdrawn from the treatment phase. | ||||||
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 |
Infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Administered every 14 days at a dose of 6 mg/kg, over a 30–90 (±15) minute intravenous infusion.
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Baseline characteristics reporting groups
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Reporting group title |
Baseline
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Reporting group description |
Frail elderly patients with wilD-type KRAS mCRC and poor prognostic factors (intermediate- or high-risk according to the KPC) received panitumumab until progression or unavveptable toxicity. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Wild-type KRAS mCRC
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Reporting group description |
Wild-type KRAS mCRC patients. Panitumumab will be administered by intravenous (i.v.) infusion at a dose of 6 mg/kg once every 14 days until disease progression is diagnosed, at which time those subjects will be withdrawn from the treatment phase. | ||
Subject analysis set title |
Mutant RAS
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Patients with mutant RAS
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Subject analysis set title |
Wild-type RAS
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Subject analysis set type |
Sub-group analysis | ||
Subject analysis set description |
Patients with wild-type RAS
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End point title |
Progression free survival (at 6 months) [1] | ||||||||
End point description |
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End point type |
Primary
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End point timeframe |
Is defined as the percentage of subjects living free of disease progression, as defined in the RECIST version 1.1 criteria, 6 months after inclusion in the study.
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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: No statistical analysis was planned for this primary outcome measure. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Objective response rate (ORR) | ||||||||
End point description |
The ORR will be estimated for confirmed values and the bilateral 95% confidence limits will be presented. Additionally, the influence of the covariables of interest (7.8 Adjustments for covariables) will be explored through a logistic regression model.
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End point type |
Secondary
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End point timeframe |
The ORR (incidence of complete response or partial response) confirmed radiologically during the treatment period.
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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 |
The OS time is defined as the number of days elapsed from the date of inclusion in the study until the date of death.
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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 |
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End point type |
Secondary
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End point timeframe |
The DCR will be defined as the time from inclusion until the date of confirmation of objective response, calculated for the subjects with an objective response.
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| No statistical analyses for this end point | |||||||||
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End point title |
Progression free survival (RAS status) | ||||||||||||
End point description |
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End point type |
Post-hoc
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End point timeframe |
At the end of follow-up.
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Statistical analysis title |
Progression free survival (RAS status) | ||||||||||||
Comparison groups |
Mutant RAS v Wild-type RAS
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Number of subjects included in analysis |
21
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Analysis specification |
Post-hoc
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Analysis type |
other | ||||||||||||
P-value |
= 0.037 | ||||||||||||
Method |
Logrank | ||||||||||||
Confidence interval |
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End point title |
Overall survival (RAS status) | ||||||||||||
End point description |
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End point type |
Post-hoc
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End point timeframe |
At the end of follow-up.
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Statistical analysis title |
Overall survival (RAS status) | ||||||||||||
Comparison groups |
Wild-type RAS v Mutant RAS
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Number of subjects included in analysis |
21
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Analysis specification |
Post-hoc
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Analysis type |
other | ||||||||||||
P-value |
= 0.745 | ||||||||||||
Method |
Logrank | ||||||||||||
Confidence interval |
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Adverse events information
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Timeframe for reporting adverse events |
The AEs were registered after the onset of the treatment.
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Adverse event reporting additional description |
Only the frequency of grade 3/5 AEs is presented. In case of a patient has more than one AE with the same SOC, PT and different intensities, only the worst grade of toxicity has been counted (all occurrences).
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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 |
12.1
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Reporting groups
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Reporting group title |
Wild-type KRAS mCRC
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Reporting group description |
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| Frequency threshold for reporting non-serious adverse events: 3% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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15 Dec 2009 |
After receiving the considerations of the participating Clinical Research Ethical Committees, changes were made in the Information Consent Form of the study as well as in the Information Consent Form of the optional biomarker study, aiming to facilitate their understanding. |
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29 Jul 2010 |
After the initial visits to the participating centers, it was found that some points of the protocol were not clear enough for the researchers.
With this relevant modification it was clarified the doubts that arose as well as facilitated the work of the health professionals who carried out the study.
1. Permit the analysis of the KRAS gene by local laboratories according to their usual clinical practice, to determine the eligibility of the patients selected to participate in the trial. The reason for this modification was to minimize the delay in the initiation of treatment in patients who had this determination, since in the hospitals of the Spanish territory it is performed by usual clinical practice in patients with metastatic colorectal cancer.
2. Clarification of inclusion criteria nº 9 and nº 10.
3. Addition of an exclusion criterion.
4. The change of the principal investigator was requested, for reasons unrelated to the promoter, from one of the participating centers in the study:
5. Correction of a typographical error of one of the participating centers that was included in the request for evaluation of the clinical trial. |
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22 Nov 2012 |
The reason for this modification was to clarify on page 39 of the protocol, point 6.4. Treatment prohibited during the study period and correct typographical error that was a source of confusion for researchers. |
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22 Jul 2013 |
The objective of this modification was to change the principal investigator in one of the centers participating in the clinical trial. |
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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. | |||
| Limitations related to the study population and design of this exploratory phase II trial involving frail elderly patients. | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/25963019 |
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