Colorectal CancerPhase 2NCT00755118
Lohp, 5-Fu/Lv and Bevacizumab, Alternative With Cpt-11, 5-Fu/Lv and Cetuximab In Metastatic Crc
A Phase 2 study testing Oxaliplatin, 5-Fluorouracil and Leucovorin in people with Colorectal Cancer, run by University Hospital of Crete at 3 sites in Greece.
Trial summary
The aim of this study is to evaluate the efficacy of the effective drugs in a alternating chemotherapy schedules in pretreated patients with mCRC, who have received all effective drugs. Read more about this study
- Who is it for?
- Ages 18 to 72 years
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- Oxaliplatin, 5-Fluorouracil and Leucovorin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 3 sitesGreece
- Study dates
- Oct 2008to Aug 2012
- 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 18 to 72 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed locally advanced or metastatic colorectal cancer
- Measurable or evaluable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST)
- ECOG performance status ≤ 2
- Age 18 - 72 years
- Patients who progress after 1st line therapy with FOLFOX/AVASTIN
- Adequate liver (Bilirubin ≤ 1.5 upper normal limit, SGOT/SGPT ≤ 4 upper normal limit, ALP ≤ 2.5 upper normal limit),renal (Creatinine ≤ 1.5 upper normal limit) and bone marrow (ANC ≥ 1,500/mm3, PLT ≥100,000/mm3) function
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- Patients must be able to understand the nature of this study
- Written informed consent
- Previous treatments with all effective drugs for metastatic colorectal cancer (CPT-11, LOHP, 5-FU/XELODA, Erbitux, Avastin)
Who cannot join
- History of serious cardiac disease (unstable angina, congestive heart failure,uncontrolled cardiac arrhythmias)
- History of myocardial infarction or stroke within 6 months
- Clinically significant peripheral vascular disease
- History of abdominal fistula, gastrointestinal perforation or intraabdominal abscess within 28 days prior to Day 0
- Major surgical procedure, open biopsy, or significant traumatic injury within 30 days prior to Day 1
- Presence of central nervous system or brain metastases
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- Evidence of bleeding diathesis or coagulopathy
- Blood pressure > 150/100 mmHg
- Pregnant or lactating woman
- Life expectancy < 3 months
- Previous radiotherapy within the last 4 weeks or > 25% of bone marrow
- Metastatic infiltration of the liver >50%
- Patients with chronic diarrhea (at least for 3 months) or partial bowel obstruction or total colectomy
- Active infection requiring antibiotics on Day 1
- Second primary malignancy, except for non-melanoma skin cancer and in situ cervical cancer
- Psychiatric illness or social situation that would preclude study compliance
Trial locations and contacts
3 sites in 1 country.
Greece3 sites
University General Hospital of Alexandroupolis, Dep of Medical Oncology
Alexandroupoli
"IASO" General Hospital of Athens, 1st Dep of Medical Oncology
Athens
University Hospital of Crete, Dep of Medical Oncology
Heraklion, Crete
About this study
Official title: Phase II Study Of Weekly Administration Oxaliplatin Plus 5-Fu/Lv (Aio Regimen) Plus Bevacizumab, Alternative With Irinotecan Plus 5-Fu/Lv(Aio Regimen) Plus Cetuximab, As Salvage Treatment In Pretreated Patients With Mcrc
The aim of this study is to evaluate the efficacy of the effective drugs in a alternating chemotherapy schedules in pretreated patients with mCRC, who have received all effective drugs.
Read the detailed description
Colorectal cancer is a major cause of death worldwide and is ranked third in incidence and deaths from cancer in the USA for men and women. Incidence and mortality have been decreasing steadily in past decades, with 5-year survival for patients diagnosed in 1996-2002, being about 65%.
Although curative surgical resection is possible in 70-80% of patients at diagnosis, almost half of them will develop local or/and metastatic recurrence and will die of the disease.
There are currently three active cytotoxic agents that have been shown to be effective in the treatment of advanced colorectal cancer: 5-Fluorouracil combined with Leucovorin (5-FU/LV), Irinotecan and Oxaliplatin. During the last few years, the median overall survival of patients with advanced CRC has been substantially increased from 12 months to about 21-22 months, when combination of these chemotherapeutic agents are administered. Combinations of 5-Fluorouracil/Leucovorin (5-FU/LV) either as bolus (Roswell Park) or infusional administration (De Gramont schedule) r weekly infusional (AIO regimen), combined with Irinotecan or Oxaliplatin accepted as the mainstay of first line treatment.
The advent of targeted therapy further expanded treatment options for patients with mCRC.In particular, inhibition of Epidermal Growth Factor Receptor (EGFR) and angiogenesis by blocking Vascular Endothelial Growth Factor (VEGF) using monoclonal antibodies, led to further improvement in the outcome of patients with mCRC.
EGFR is expressed by most CRCs. Cetuximab (Erbitux) is a chimeric monoclonal antibody that specifically targets EGFR. In combination with Irinotecan, Cetuximab is approved for the treatment of EGFR-expressing mCRC, that has failed prior Irinotecan-based therapy, suggesting that Cetuximab may circumvent Irinotecan resistance.
Bevacizumab (Avastin) is a monoclonal antibody against Vascular Endothelial Growth Factor (VEGF). In CRC, increased VEGF expression correlates with invasiveness, vascular density, metastasis, recurrence and prognosis.
In a phase 2 trial of treatment of CRC, the addition of bevacizumab to FU/LV increased the response rate, the median time to disease progression, and the median duration of survival. Recently, it has been shown in randomized phase 2 trials that bevacizumab, when combined with irinotecan plus bolus FU/LV in the first line treatment of metastatic CRC, and with oxaliplatin plus continuous FU/LV (FOLFOX) in second-line treatment leads to an increased median survival, progression-free survival (PFS), and response rate compared with cytotoxic chemotherapy alone.
- Conditions
- Colorectal Cancer
- Being tested
- Oxaliplatin, 5-Fluorouracil, Leucovorin, Bevacizumab, Irinotecan
- Keywords
- Metastatic colorectal cancer, Second line, Irinotecan, Cetuximab, Bevacizumab
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
OxaliplatinDrug
Also called Eloxatin, LoHP
Oxaliplatin (I.V) 85mg/m2 on week 1 and week 3 every six weeks for 2 continuously until disease progression or the appearance of unacceptable toxicity
5-FluorouracilDrug
Also called 5-FU
5-Fluorouracil (I.V) 1750mg/m2 on week 1,2,3 and 4 every six weeks for 2 continuously until disease progression or the appearance of unacceptable toxicity
LeucovorinDrug
Also called LV
Leucovorin (I.V) 500mg/m2 on week 1,2,3 and 4 every six weeks for 2 continuously until disease progression or the appearance of unacceptable toxicity
BevacizumabDrug
Also called Avastin
Bevacizumab (I.V) 10mg/Kg on week 1 and week 3 every six weeks for 2 continuously until disease progression or the appearance of unacceptable toxicity
IrinotecanDrug
Also called CPT-11, Campto
Irinotecan (I.V) 110mg/m2 on week 2 and week 4 every six weeks for 2 continuously until disease progression or the appearance of unacceptable toxicity
CetuximabDrug
Also called Erbitux
Cetuximab (I.V) 500mg/m2 on week 2 and week 4 every six weeks for 2 continuously until disease progression or the appearance of unacceptable toxicity
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | LoHP/AIO/Avastin->CPT-11/AIO/Erbitux Receives: Drug: Oxaliplatin; Drug: 5-Fluorouracil; Drug: Leucovorin; Drug: Bevacizumab; Drug: Irinotecan; Drug: Cetuximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate
Measured: 3 - 6 month
Secondary outcomes (5)
Time To Progression
Measured: 1 year
Toxicity profile
Measured: 28 days
Quality of life
Measured: 28 days
Symptoms improvement
Measured: 28 days
Overall Survival
Measured: Probability of 1-year survival (%)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Sep 2008 (estimated)
- Study startOct 2008
- Primary completionAug 2012
- Study completionAug 2012
Why it stopped: Due to poor Accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital of Crete
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Vassilis Georgoulias, MD, University Hospital of Crete
- Investigators
- Nikos Vardakis, MD, Principal investigator, University Hospital of Crete, Dep of Medical Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00755118
- Sponsor's protocol ID
- CT/08.28
- Status last verified
- Oct 2015
- First submitted
- 17 Sep 2008
- Last updated
- 7 Oct 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study Of Weekly Administration Oxaliplatin Plus 5-Fu/Lv (Aio Regimen) Plus Bevacizumab, Alternative With Irinotecan Plus 5-Fu/Lv(Aio Regimen) Plus Cetuximab, As Salvage Treatment In Pretreated Patients With Mcrc
- ClinicalTrials.gov ID
- NCT00755118
- Acronym / sponsor ID
- CT/08.28
- Conditions
- Colorectal Cancer
- Keywords
- Metastatic colorectal cancer, Second line, Irinotecan, Cetuximab, Bevacizumab
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Due to poor Accrual
- Enrolment
- 24 participants (actual)
- Lead sponsor
- University Hospital of CreteUniversity, hospital or other
- Study start
- Oct 2008
- Primary completion
- Aug 2012 (actual)
- Study completion
- Aug 2012 (actual)
- First posted
- 18 Sep 2008 (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.
The aim of this study is to evaluate the efficacy of the effective drugs in a alternating chemotherapy schedules in pretreated patients with mCRC, who have received all effective drugs.
Detailed description
Colorectal cancer is a major cause of death worldwide and is ranked third in incidence and deaths from cancer in the USA for men and women. Incidence and mortality have been decreasing steadily in past decades, with 5-year survival for patients diagnosed in 1996-2002, being about 65%.
Although curative surgical resection is possible in 70-80% of patients at diagnosis, almost half of them will develop local or/and metastatic recurrence and will die of the disease.
There are currently three active cytotoxic agents that have been shown to be effective in the treatment of advanced colorectal cancer: 5-Fluorouracil combined with Leucovorin (5-FU/LV), Irinotecan and Oxaliplatin. During the last few years, the median overall survival of patients with advanced CRC has been substantially increased from 12 months to about 21-22 months, when combination of these chemotherapeutic agents are administered. Combinations of 5-Fluorouracil/Leucovorin (5-FU/LV) either as bolus (Roswell Park) or infusional administration (De Gramont schedule) r weekly infusional (AIO regimen), combined with Irinotecan or Oxaliplatin accepted as the mainstay of first line treatment.
The advent of targeted therapy further expanded treatment options for patients with mCRC.In particular, inhibition of Epidermal Growth Factor Receptor (EGFR) and angiogenesis by blocking Vascular Endothelial Growth Factor (VEGF) using monoclonal antibodies, led to further improvement in the outcome of patients with mCRC.
EGFR is expressed by most CRCs. Cetuximab (Erbitux) is a chimeric monoclonal antibody that specifically targets EGFR. In combination with Irinotecan, Cetuximab is approved for the treatment of EGFR-expressing mCRC, that has failed prior Irinotecan-based therapy, suggesting that Cetuximab may circumvent Irinotecan resistance.
Bevacizumab (Avastin) is a monoclonal antibody against Vascular Endothelial Growth Factor (VEGF). In CRC, increased VEGF expression correlates with invasiveness, vascular density, metastasis, recurrence and prognosis.
In a phase 2 trial of treatment of CRC, the addition of bevacizumab to FU/LV increased the response rate, the median time to disease progression, and the median duration of survival. Recently, it has been shown in randomized phase 2 trials that bevacizumab, when combined with irinotecan plus bolus FU/LV in the first line treatment of metastatic CRC, and with oxaliplatin plus continuous FU/LV (FOLFOX) in second-line treatment leads to an increased median survival, progression-free survival (PFS), and response rate compared with cytotoxic chemotherapy alone.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Oxaliplatin, Drug: 5-Fluorouracil, Drug: Leucovorin, Drug: Bevacizumab, Drug: Irinotecan, Drug: CetuximabLoHP/AIO/Avastin->CPT-11/AIO/Erbitux |
Who may qualify
- Ages
- 18 to 72 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Histologically confirmed locally advanced or metastatic colorectal cancer
- Measurable or evaluable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST)
- ECOG performance status ≤ 2
- Age 18 - 72 years
- Patients who progress after 1st line therapy with FOLFOX/AVASTIN
Key exclusion criteria (16 listed)
- History of serious cardiac disease (unstable angina, congestive heart failure,uncontrolled cardiac arrhythmias)
- History of myocardial infarction or stroke within 6 months
- Clinically significant peripheral vascular disease
- History of abdominal fistula, gastrointestinal perforation or intraabdominal abscess within 28 days prior to Day 0
- Major surgical procedure, open biopsy, or significant traumatic injury within 30 days prior to Day 1
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 |
|---|---|---|
| OxaliplatinAlso: Eloxatin, LoHPOxaliplatin (I.V) 85mg/m2 on week 1 and week 3 every six weeks for 2 continuously until disease progression or the appearance of unacceptable toxicity | Drug | 1 |
| 5-FluorouracilAlso: 5-FU5-Fluorouracil (I.V) 1750mg/m2 on week 1,2,3 and 4 every six weeks for 2 continuously until disease progression or the appearance of unacceptable toxicity | Drug | 1 |
| LeucovorinAlso: LVLeucovorin (I.V) 500mg/m2 on week 1,2,3 and 4 every six weeks for 2 continuously until disease progression or the appearance of unacceptable toxicity | Drug | 1 |
| BevacizumabAlso: AvastinBevacizumab (I.V) 10mg/Kg on week 1 and week 3 every six weeks for 2 continuously until disease progression or the appearance of unacceptable toxicity | Drug | 1 |
| IrinotecanAlso: CPT-11, CamptoIrinotecan (I.V) 110mg/m2 on week 2 and week 4 every six weeks for 2 continuously until disease progression or the appearance of unacceptable toxicity | Drug | 1 |
| CetuximabAlso: ErbituxCetuximab (I.V) 500mg/m2 on week 2 and week 4 every six weeks for 2 continuously until disease progression or the appearance of unacceptable toxicity | Drug | 1 |
Primary outcome
Objective Response Rate
Time frame: 3 - 6 month
5 secondary outcomes
Time To Progression
Time frame: 1 year
Toxicity profile
Time frame: 28 days
Quality of life
Time frame: 28 days
Symptoms improvement
Time frame: 28 days
Overall Survival
Time frame: Probability of 1-year survival (%)
Results and safety
The study was stopped early (reason given: Due to poor Accrual). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Oct 2015.
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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.
Nikos Vardakis, MD principal investigator
University Hospital of Crete, Dep of Medical Oncology
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Oxaliplatin, 5-Fluorouracil and Leucovorin in people with Colorectal Cancer, run by University Hospital of Crete at 3 sites in Greece.
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 9 inclusion and 16 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 7 Oct 2015. 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 Greece. 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: Due to 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?
Objective Response Rate (time frame: 3 - 6 month). 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 7 Oct 2015.