Colorectal Cancer MetastaticPhase 2NCT01522612
Colorectal Cancer (CRC) Cetuximab Elderly Frail
A Phase 2 study testing Cetuximab, 5-fluorouracil and leucovorin in people with Colorectal Cancer Metastatic, run by European Organisation for Research and Treatment of Cancer - EORTC at 3 sites in 3 countries.
Trial summary
OBJECTIVE: The principal objective of the trial is to evaluate whether the addition of cetuximab associated with 5-fluorouracil in elderly patients with KRAS wild type advanced colorectal cancer (CRC) prolongs Progression Free Survival, compared with 5-fluorouracil alone. Read more about this study
- Who is it for?
- Ages 70 years and older
- Conditions the study is for
- Colorectal Cancer Metastatic
- What is being tested?
- Cetuximab, 5-fluorouracil and leucovorin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 3 sitesin 3 countries
- Study dates
- Apr 2013to Jan 2015
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 70 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- Pathologically confirmed metastatic colorectal cancer
- Measurable disease according to RECIST V1.1
- Histological local review and analysis of KRAS
- Age ≥ 80 or ≥ 70 in combination with functional restrictions defined as limitation in at least 2 of 8 IADL
- WHO performance status 0, 1 or 2
- Adequate bone marrow reserves, hepatic function \& renal function
- Normal 12 lead ECG without clinically significant abnormalities
- Written informed consent before randomization according to ICH/EU GCP, and local, national and international regulations
Who cannot join
- Prior systemic chemotherapy for metastatic disease
- Previous exposure to EGFR or VEGF/VEGFR targeted therapy
- Patients may have received chemotherapy in the adjuvant or neoadjuvant setting (CRC). The treatment-free interval should be 6 months or more from the end of (neo-)adjuvant therapy
- Previous radiotherapy, either in the adjuvant setting or for the treatment of bone metastases, is allowed provided that the measurable lesions are outside the radiation fields
- Persistence of clinically relevant treatment-related toxicities from previous chemotherapy and/or radiotherapy (adjuvant or neo-adjuvant setting)
- Treatment with other investigational drugs or treatment in another clinical trial within the past four weeks before start of treatment or concomitantly with this trial
Show all 12Show fewer
- Known alcohol or drug abuse
- Clinically significant cardiovascular disease
- Evidence of uncontrolled medical comorbidities despite adequate treatment
- Patients who have suffered a cerebrovascular accident or transient ischemic attack within the past 12 months
- History, within the past 5 years, of malignancies other than CRC
- Psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and followup schedule
Trial locations and contacts
3 sites in 3 countries.
3 sites in 3 countries
About this study
Official title: Treatment of Patients With KRAS Wild Type Advanced Colorectal Cancer (CRC) With 5-Fluorouracil (5-FU) or 5- FU Plus an Epidermal Growth Factor Receptor (EGFR) Inhibitor (Cetuximab) Based on a Comprehensive Geriatric Assessment (CGA).
OBJECTIVE: The principal objective of the trial is to evaluate whether the addition of cetuximab associated with 5-fluorouracil in elderly patients with KRAS wild type advanced colorectal cancer (CRC) prolongs Progression Free Survival, compared with 5-fluorouracil alone.
Read the detailed description
The primary efficacy analyses will be performed on the Intention-to-treat population.
The safety analyses will be performed on the Safety population.
- Median PFS and OS in each treatment arm with its 95% CI, estimated by the Kaplan-Meier technique
- Response rates by treatment arm with their exact 95% CI
- IADL sum score, G8 sum score and social situation by treatment arm at baseline and at each timepoint of assessment
- QoL scores from the EORTC QLQ-C30 and QLQ-ELD14 modules by treatment arm at baseline and at each timepoint of assessment
- Safety data by treatment arm in the Safety population. Worst toxicity grade over all cycles according to the CTCAE criteria version 4.0 by treatment arm.
- Pharmaco-economics evaluation
Summary of proposed Phase II trial characteristics:
- Total number of randomized patients: 150.
- Total number of events at phase II analysis for primary endpoint: 110.
- Total number of patients screened over the phase II: 250.
- Total number of patients treated with cetuximab for the Phase II study: 75.
- Maximum study duration: 19 months.
In the present study, HRQoL is an important secondary endpoint. The objective of the HRQoL data collection in this Phase II trial is to assess the impact of the addition of cetuximab on patients' HRQoL during treatment.
The hypothesis is that there will be no difference in patients' HRQoL between both treatment arms during treatment. The HRQoL domains (from the EORTC QLQ-C30 module) which are expected to be affected by treatment (to the same extent in both arms) are Global health status, Fatigue, Pain and Stool habits.
- Conditions
- Colorectal Cancer Metastatic
- Being tested
- Cetuximab, 5-fluorouracil, leucovorin
- Keywords
- KRAS Wild Type, Frail Elderly, QLQ-C30, QLQ-ELD14, CGA, EGFR, Cetuximab, 5-FU
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CetuximabDrug
Also called Erbitux
500 mg/m2 on day 1, Every 14 days Intravenously
5-fluorouracilDrug
Also called 5-FU
Every 2 weeks, 400 mg/m2 on day 1; 2400 mg/m2 from day 1 to day 3, intravenously
leucovorinDrug
Also called Folinic Acid
Every 2 weeks, Racemic leucovorin 200 mg/m2 or l-leucovorin 100 mg/m2 on day 1, intravenously
| Study group | Role | What they receive |
|---|---|---|
| 5-fluorouracil/leucovorin plus cetuximab | Experimental | Not described Receives: Drug: Cetuximab; Drug: 5-fluorouracil; Drug: leucovorin |
| 5-fluorouracil/leucovorin alone | Active comparator | Not described Receives: Drug: 5-fluorouracil; Drug: leucovorin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression free survival
Progression will be defined according to the "RECIST V1.1"
Measured: 19 months from first patient in
Secondary outcomes (11)
Overall Survival
Measured: 19 months from first patient in
Response Rate
according to the RECIST V1.1
Measured: 19 months from first patient in
Change in Instrumental Activities of Daily Living (IADL) score
Measured: 19 months from first patient in
Change in G8 geriatric assessment screening tool
Measured: 19 months from first patient in
Change in social situation
Measured: 19 months from first patient in
Score of Quality of Life (EORTC-QLQ C30 and QLQ-ELD14)
Measured: 14 days before randomization; 6 weeks, 14 weeks, 22 weeks and 38 weeks after randomization; 30 days after last treatment administration
Occurrence of adverse events
Adverse events will be graded according to the "Common Terminology Criteria for Adverse events" CTCAE,version 4.0.
Measured: 19 months from first patient in
Health Economy assessments
Measured: 19 months from first patient in
Score of elderly minimal dataset comprehensive geriatric assessment (EMDCGA), as evaluated by G8 instrument
Measured: 14 days before randomization; 6 weeks, 14 weeks, 22 weeks and 38 weeks after randomization; 30 days after last treatment administration
Score of elderly minimal dataset comprehensive geriatric assessment (EMDCGA), as evaluated by Instrumental Activities of Daily Life (IADL) questionnaire
Measured: 14 days before randomization; 6 weeks, 14 weeks, 22 weeks and 38 weeks after randomization; 30 days after last treatment administration
Score of elderly minimal dataset comprehensive geriatric assessment (EMDCGA), as evaluated by social situation questionnaire
Measured: 14 days before randomization; 6 weeks, 14 weeks, 22 weeks and 38 weeks after randomization; 30 days after last treatment administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2012 (estimated)
- Study startApr 2013
- Primary completionJan 2015
- Study completionJan 2015
Why it stopped: poor accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal Cancer MetastaticStudies of the same condition, open and under way.
- More trials run by European Organisation for Research and Treatment of Cancer - EORTCThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Sponsor type
- Research network
- Collaborators
- Merck KGaA, Darmstadt, Germany
- Responsible party
- Sponsor
- Investigators
- Marc Peeters, MD, PhD, Study chair, UNIVERSITAIR ZIEKENHUIS ANTWERPEN, Edegem, BelgiumUlrich Wedding, MD, Study chair, UNIVERSITAETSKLINIKUM JENA, Jena, Germany
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01522612
- Sponsor's protocol ID
- EORTC-40085-75083
- Other IDs
- 2011-002947-83
- Status last verified
- Jun 2016
- First submitted
- 27 Jan 2012
- Last updated
- 10 Jun 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 10 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment of Patients With KRAS Wild Type Advanced Colorectal Cancer (CRC) With 5-Fluorouracil (5-FU) or 5- FU Plus an Epidermal Growth Factor Receptor (EGFR) Inhibitor (Cetuximab) Based on a Comprehensive Geriatric Assessment (CGA).
- ClinicalTrials.gov ID
- NCT01522612
- Acronym / sponsor ID
- EORTC-40085-75083
- Conditions
- Colorectal Cancer Metastatic
- Keywords
- KRAS Wild Type, Frail Elderly, QLQ-C30, QLQ-ELD14, CGA, EGFR, Cetuximab, 5-FU
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: poor accrual
- Enrolment
- 5 participants (actual)
- Lead sponsor
- European Organisation for Research and Treatment of Cancer - EORTCResearch network
- Collaborators
- Merck KGaA, Darmstadt, Germany
- Study start
- Apr 2013
- Primary completion
- Jan 2015 (actual)
- Study completion
- Jan 2015 (actual)
- First posted
- 31 Jan 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
OBJECTIVE: The principal objective of the trial is to evaluate whether the addition of cetuximab associated with 5-fluorouracil in elderly patients with KRAS wild type advanced colorectal cancer (CRC) prolongs Progression Free Survival, compared with 5-fluorouracil alone.
Detailed description
The primary efficacy analyses will be performed on the Intention-to-treat population.
The safety analyses will be performed on the Safety population.
- Median PFS and OS in each treatment arm with its 95% CI, estimated by the Kaplan-Meier technique
- Response rates by treatment arm with their exact 95% CI
- IADL sum score, G8 sum score and social situation by treatment arm at baseline and at each timepoint of assessment
- QoL scores from the EORTC QLQ-C30 and QLQ-ELD14 modules by treatment arm at baseline and at each timepoint of assessment
- Safety data by treatment arm in the Safety population. Worst toxicity grade over all cycles according to the CTCAE criteria version 4.0 by treatment arm.
- Pharmaco-economics evaluation
Summary of proposed Phase II trial characteristics:
- Total number of randomized patients: 150.
- Total number of events at phase II analysis for primary endpoint: 110.
- Total number of patients screened over the phase II: 250.
- Total number of patients treated with cetuximab for the Phase II study: 75.
- Maximum study duration: 19 months.
In the present study, HRQoL is an important secondary endpoint. The objective of the HRQoL data collection in this Phase II trial is to assess the impact of the addition of cetuximab on patients' HRQoL during treatment.
The hypothesis is that there will be no difference in patients' HRQoL between both treatment arms during treatment. The HRQoL domains (from the EORTC QLQ-C30 module) which are expected to be affected by treatment (to the same extent in both arms) are Global health status, Fatigue, Pain and Stool habits.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 5-fluorouracil/leucovorin plus cetuximab | Experimental | Drug: Cetuximab, Drug: 5-fluorouracil, Drug: leucovorin |
| 5-fluorouracil/leucovorin alone | Active comparator | Drug: 5-fluorouracil, Drug: leucovorin |
Who may qualify
- Ages
- 70 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (8 listed)
- Pathologically confirmed metastatic colorectal cancer
- Measurable disease according to RECIST V1.1
- Histological local review and analysis of KRAS
- Age ≥ 80 or ≥ 70 in combination with functional restrictions defined as limitation in at least 2 of 8 IADL
- WHO performance status 0, 1 or 2
Key exclusion criteria (12 listed)
- Prior systemic chemotherapy for metastatic disease
- Previous exposure to EGFR or VEGF/VEGFR targeted therapy
- Patients may have received chemotherapy in the adjuvant or neoadjuvant setting (CRC). The treatment-free interval should be 6 months or more from the end of (neo-)adjuvant therapy
- Previous radiotherapy, either in the adjuvant setting or for the treatment of bone metastases, is allowed provided that the measurable lesions are outside the radiation fields
- Persistence of clinically relevant treatment-related toxicities from previous chemotherapy and/or radiotherapy (adjuvant or neo-adjuvant setting)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CetuximabAlso: Erbitux500 mg/m2 on day 1, Every 14 days Intravenously | Drug | 5-fluorouracil/leucovorin plus cetuximab |
| 5-fluorouracilAlso: 5-FUEvery 2 weeks, 400 mg/m2 on day 1; 2400 mg/m2 from day 1 to day 3, intravenously | Drug | 5-fluorouracil/leucovorin alone, 5-fluorouracil/leucovorin plus cetuximab |
| leucovorinAlso: Folinic AcidEvery 2 weeks, Racemic leucovorin 200 mg/m2 or l-leucovorin 100 mg/m2 on day 1, intravenously | Drug | 5-fluorouracil/leucovorin alone, 5-fluorouracil/leucovorin plus cetuximab |
Primary outcome
Progression free survival
Time frame: 19 months from first patient in
Progression will be defined according to the "RECIST V1.1"
11 secondary outcomes
Overall Survival
Time frame: 19 months from first patient in
Response Rate
Time frame: 19 months from first patient in
Change in Instrumental Activities of Daily Living (IADL) score
Time frame: 19 months from first patient in
Change in G8 geriatric assessment screening tool
Time frame: 19 months from first patient in
Change in social situation
Time frame: 19 months from first patient in
Score of Quality of Life (EORTC-QLQ C30 and QLQ-ELD14)
Time frame: 14 days before randomization; 6 weeks, 14 weeks, 22 weeks and 38 weeks after randomization; 30 days after last treatment administration
Occurrence of adverse events
Time frame: 19 months from first patient in
Health Economy assessments
Time frame: 19 months from first patient in
Score of elderly minimal dataset comprehensive geriatric assessment (EMDCGA), as evaluated by G8 instrument
Time frame: 14 days before randomization; 6 weeks, 14 weeks, 22 weeks and 38 weeks after randomization; 30 days after last treatment administration
Score of elderly minimal dataset comprehensive geriatric assessment (EMDCGA), as evaluated by Instrumental Activities of Daily Life (IADL) questionnaire
Time frame: 14 days before randomization; 6 weeks, 14 weeks, 22 weeks and 38 weeks after randomization; 30 days after last treatment administration
Score of elderly minimal dataset comprehensive geriatric assessment (EMDCGA), as evaluated by social situation questionnaire
Time frame: 14 days before randomization; 6 weeks, 14 weeks, 22 weeks and 38 weeks after randomization; 30 days after last treatment administration
Results and safety
The study was stopped early (reason given: poor accrual). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jun 2016.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marc Peeters, MD, PhD study chair
UNIVERSITAIR ZIEKENHUIS ANTWERPEN, Edegem, Belgium
Ulrich Wedding, MD study chair
UNIVERSITAETSKLINIKUM JENA, Jena, Germany
3 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cetuximab, 5-fluorouracil and leucovorin in people with Colorectal Cancer Metastatic, run by European Organisation for Research and Treatment of Cancer - EORTC at 3 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 10 Jun 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Belgium, Cyprus, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: poor accrual). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression free survival (time frame: 19 months from first patient in). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jun 2016.