Clinical Trial Results:
Phase IV, multicentric study to evaluate correlation between global objectives response according RECIST v1.1 criteria evaluated by conventional images tecniques with morfologic response by TAC and pathologic response after hepatic metastatic resectability secondary to colorectal cancer in treatment with bevacizumab and XELOX.
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Summary
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EudraCT number |
2011-000143-24 |
Trial protocol |
ES |
Global end of trial date |
18 Dec 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
20 Feb 2019
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First version publication date |
20 Feb 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 |
GEMCAD-10-06
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01493713 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
GEMCAD group
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Sponsor organisation address |
Secretari Coloma, 64-68, esc. B, entlo. 5ª, Barcelona, Spain, 08024
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Public contact |
Ruth Vera
GEMCAD
Secretari Coloma, 64-68, esc. B, entlo. 5ª
08024 Barcelona
, GEMCAD, 34 848 422 091, ruth.vera.garcia@cfnavarra.es
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Scientific contact |
Ruth Vera
GEMCAD
Secretari Coloma, 64-68, esc. B, entlo. 5ª
08024 Barcelona
, GEMCAD, 34 848 422 091, ruth.vera.garcia@cfnavarra.es
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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 |
07 Nov 2018
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
18 Dec 2017
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Global end of trial reached? |
Yes
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Global end of trial date |
18 Dec 2017
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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 |
Correlation between global objectives response according RECIST v1.1 criteria evaluated by conventional images tecniques with morfologic response by TAC and pathologic response after hepatic metastatic resectability.
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Protection of trial subjects |
All patients signed an ICF and all data were properly anonymized to ensure data protection. Data recorded on source documents was transcribed onto a validated data collection instrument (an electronic case report form) provided by Pivotal. The investigator ensured the accuracy and completeness of the data reported, and its consistency with the source documentation.
Data were collected on all subjects who provide written informed consent.
The primary source document for this study was the subject’s medical record. If separate research records were maintained by the investigator(s), both the medical record and the research records were monitored/audited for the purposes of the study.
Study documents (including subject records, copies of collected data, study notebook, and pharmacy records) were kept secured in accordance with site practices and applicable regulatory requirements.
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Background therapy |
Clinical study of bevacizumab with XELOX in patients with potentially resectable hepatic metastases of CRC, as front-line treatment. | ||
Evidence for comparator |
This was a one arm clinical trial, no comparator was present. | ||
Actual start date of recruitment |
15 Jul 2011
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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 |
Spain: 83
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Worldwide total number of subjects |
83
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EEA total number of subjects |
83
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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 |
47
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85 years and over |
0
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Recruitment
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Recruitment details |
83 patients were screened and included at 23 Spanish sites | ||||||||||
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Pre-assignment
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Screening details |
Patients with the diagnosis of liver metastasis presenting synchronically or after a disease-free interval. The primary tumor shall have been resected previously although the inverse approach may be acceptable if the tumor is not very symptomatic. | ||||||||||
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Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||
Blinding implementation details |
Not applicable
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Arms
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Arm title
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Study arm | ||||||||||
Arm description |
Firstly, patients received 4 cycles of treatment with bevacizumab + XELOX. Then, depending on a radiologic evaluation with conventional CT and assessment of the patient by a multidisciplinary team consisting of an oncologist and surgeon, patients who were candidates for surgery received another treatment cycle without bevacizumab, i.e., with XELOX alone, and they underwent surgical resection of liver metastases. The rest of the patients, who were not candidates for surgery after this first evaluation, continued with the same schedule of bevacizumab + XELOX treatment until hepatic resection is possible or until progression, the occurrence of unacceptable toxicity, or the patient withdraws informed consent. Patients in whom liver metastases were resected after the initial treatment (5 treatment cycles) continued later with the same treatment schedule until completing a maximum of 6 cycles. Overall, patients received a maximum of 12 treatment cycles. | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
Bevacizumab
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Investigational medicinal product code |
bevacizumab
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Other name |
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Pharmaceutical forms |
Concentrate and solvent for concentrate for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Bevacizumab: 7.5 mg/kg on day 1 of every 3-week cycle
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Investigational medicinal product name |
capecitabine
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Investigational medicinal product code |
capecitabine
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Other name |
xeloda
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Pharmaceutical forms |
Buccal tablet
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Routes of administration |
Oral use
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Dosage and administration details |
Capecitabine: 1000 mg/m2 orally, 2 times a day, days 1 to 14 every 3 weeks
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Investigational medicinal product name |
oxaliplatin
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Investigational medicinal product code |
oxaliplatin
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Other name |
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Pharmaceutical forms |
Concentrate and solvent for concentrate for solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Oxaliplatin: 130 mg/m2 i.v. administered in a 2-hour infusion on day 1, every 3 weeks
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Baseline characteristics reporting groups
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Reporting group title |
Overall trial
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Reporting group description |
All patients had adenocarcinoma histology, and most tumors were located in left colon (58 [69.88%]). Metastatic disease was present at first diagnosis in 58 (69.88%) patients. Thirteen patients (15.66%) had received previous adjuvant quemotherapy. KRAS was obtained for 79 patients. Thirty-six patients had mutated KRAS and 43 patients were wild-type KRAS. Besides this characteristic, both subgroups were similar in terms of sex, age and demographics. ITT population comprised 78 patients as five patients were considered screening failure and did not start treatment.Most patients had an ECOG functional status 0 (64 patients, 77.11%), while 18 (21.69%) were ECOG 1. Thirteen patients had received adjuvant chemotherapy and two patients had previously received radiotherapy.Seventy-two patients had undergone previous surgery, 51 out of them had a radical surgery. In total, 43 patients (51.81%) had wild type KRAS, whereas 36 (43.37%) had KRAS mutated. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Study arm
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Reporting group description |
Firstly, patients received 4 cycles of treatment with bevacizumab + XELOX. Then, depending on a radiologic evaluation with conventional CT and assessment of the patient by a multidisciplinary team consisting of an oncologist and surgeon, patients who were candidates for surgery received another treatment cycle without bevacizumab, i.e., with XELOX alone, and they underwent surgical resection of liver metastases. The rest of the patients, who were not candidates for surgery after this first evaluation, continued with the same schedule of bevacizumab + XELOX treatment until hepatic resection is possible or until progression, the occurrence of unacceptable toxicity, or the patient withdraws informed consent. Patients in whom liver metastases were resected after the initial treatment (5 treatment cycles) continued later with the same treatment schedule until completing a maximum of 6 cycles. Overall, patients received a maximum of 12 treatment cycles. | ||
Subject analysis set title |
one arm
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
Primary endpoint was the correlation of global objective responses according to RECIST criteria v1.1. evaluated by conventional imaging techniques, with the morphological and the pathological response after resection of liver metastases.
Objective response rate was assessed on the ITT population (83 patients).
Sixty-eight patients were evaluated by RECIST, with 33 patients matching partial response, 30 patients reaching stable disease and five patients progressive disease. Morphological assessment was performed in 67 patients (27 optimal responses, 34 incomplete responses, 6 null responses). Fifty-nine patients underwent surgery and 22 patients completed four post-surgery cycles with bevacizumab + XELOX.
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End point title |
RECIST versus morphologic and pathologic responses [1] | ||||||
End point description |
Primary endpoint was the correlation of global objective responses according to RECIST criteria v1.1. evaluated by conventional imaging techniques, with the morphological and the pathological response after resection of liver metastases.
Objective response rate was assessed on the ITT population (83 patients).
Sixty-eight patients were evaluated by RECIST, with 33 patients matching partial response, 30 patients reaching stable disease and five patients progressive disease. Morphological assessment was performed in 67 patients (27 optimal responses, 34 incomplete responses, 6 null responses). Fifty-nine patients underwent surgery and 22 patients completed four post-surgery cycles with bevacizumab + XELOX.
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End point type |
Primary
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End point timeframe |
along 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: Primary endpoint was the correlation of global objective responses according to RECIST criteria v1.1. evaluated by conventional imaging techniques, with the morphological and the pathological response after resection of liver metastases. Objective response rate was assessed on the ITT population (83 patients). Sixty-eight patients were evaluated by RECIST, with 33 patients matching partial response, 30 patients reaching stable disease and five patients progressive disease. |
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| No statistical analyses for this end point | |||||||
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End point title |
Progression free survival | ||||||||
End point description |
Progression free survival (PFS) was defined as the time, calculated in months, elapse from the date when the patient signed the informed consent form and the date of disease progression or death from any cause. For those patients that did not present any event (death/ disease progression), the date of the last visit was considered.
In patients undergoing metastases surgery (R0, R1, R2) PFS was defined as the time from when patient started treatment till any of the following events:
-Recurrence or progressive disase after surgery.
-Death.
In patients who did not undergo metastases surgery, PFS was defined as time from patient started treatment until any of the following:
-Progressive disease (if it happens before or after scheduled surgery).
-Death.
Median PFS in patients with resected metastases was 21.14 months, whereas in those patients with non-resected metastases, median PFS was 4.6 months (p<0.0001).
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End point type |
Secondary
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End point timeframe |
Along the study
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| No statistical analyses for this end point | |||||||||
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End point title |
Recurrence Free Survival | ||||||||
End point description |
Those patients with metastases resection have been analyzed for this purpose (n=49), including R0, R1 and R2.
RFS is defined as the interval from surgery to disease progression. Those patients receiving XELOX + bevacizumab post-metastasectomy, or who have changed treatment without prior progressive disease, were censored at the time of their last prior XELOX + bevacizumab cycle.
Median RFS was 10.32 months.
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End point type |
Secondary
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End point timeframe |
Along the study.
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| No statistical analyses for this end point | |||||||||
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End point title |
Overall survival | ||||||||
End point description |
Overall survival (OS) for the entire study population is included in this section. An event was considered as those patient that died during the study. It was calculated as the time in months since the date when the patient signed the informed consent until death.
For those patient that did not die during the follow-up period of the study, it was considered as the last contact with them. In this graphic, it is included the information of all patients that signed the informed consent form.
Median OS was not reached as 59.82% patients were alive at the time of the analysis.
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End point type |
Secondary
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End point timeframe |
Along the study.
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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 |
Up to 30 days after lasto study drugs dose
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Adverse event reporting additional description |
CTCAE 4.03
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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 |
4.03
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Reporting groups
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Reporting group title |
Safety population
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Reporting group description |
The tolerability analysis was performed in the safety population, i.e. the set of patients who had received at least one dose of the treatment. The safety analysis was performed by treatment received. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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24 Jun 2011 |
some typos were clarified and additional information was provided to improve consistency in an exclusion criterion. A prospective translational study was added to look for predictive biomarkers. Additional sites were included. |
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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. | |||
| The main limitation of this study is the relatively small sample size, such that statistical differences between KRAS mutated and wild-type were not demonstrated for any parameter. | |||
