Colorectal CancerPhase 3NCT00797485
Bevacizumab and Combination Chemotherapy in Treating Patients With Previously Untreated Metastatic Colorectal Cancer That Cannot Be Removed By Surgery
A Phase 3 study testing bevacizumab, capecitabine and fluorouracil in people with Colorectal Cancer, run by Southern Italy Cooperative Oncology Group at 1 site in Italy.
Trial summary
RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- bevacizumab, capecitabine and fluorouracil
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 672 participants
- Where
- 1 siteItaly
- Study dates
- Jul 2008to Jul 2011
- Phase
- Phase 3
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS:
- Histologically or cytologically confirmed colorectal cancer
- Metastatic disease that is not amenable to surgery
- At least one measurable lesion according to RECIST criteria
- No untreated brain metastases or spinal cord compression
PATIENT CHARACTERISTICS:
- ECOG performance status 0-1
- Life expectancy ≥ 12 weeks
- Hemoglobin ≥ 9.0 g/dL
- ANC ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
- AST and/or ALT ≤ 2.5 times ULN (< 5 times ULN if liver metastases present)
- Alkaline phosphatase ≤ 2.5 times ULN (< 5 times ULN if liver metastases present)
- PT-INR/PTT < 1.5 times ULN
- Creatinine clearance > 50 mL/min OR serum creatinine ≤ 1.5 times ULN
- Proteinuria on dipstick urinalysis < 2+ OR 24-hour urine protein ≤ 1g
- Not pregnant or nursing
- Negative pregnancy test
- Must be accessible for treatment and follow-up
- No history of inflammatory bowel disease and/or acute or subacute bowel occlusion
- No serious non-healing wound, ulcer, or bone fracture
- No evidence of bleeding diathesis or coagulopathy
- No uncontrolled hypertension
- No clinically significant cardiovascular disease including any of the following:
- Cerebrovascular accident within the past 6 months
- Myocardial infarction within the past 6 months
- Unstable angina
- New York Heart Association grade II-IV congestive heart failure
- Serious cardiac arrhythmia requiring medication
- No known allergy to Chinese hamster ovary cell proteins or any of the components of the study medications
- No other malignancy within the past 5 years except basal cell and squamous cell skin cancer or carcinoma in situ of the cervix
- No significant traumatic injury within the past 28 days
- No substance abuse or medical, psychological, or social conditions that may interfere with participation in the study or the evaluation of study results
- Able to swallow oral medications
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- At least 6 months since prior adjuvant treatment
- No prior irinotecan and/or bevacizumab during prior adjuvant therapy
- No prior cytotoxic drugs for the metastatic disease
- More than 10 days since prior and no concurrent anticoagulants for therapeutic purposes
- No chronic, daily treatment with high-dose aspirin (> 325 mg/day) or other medications known to predispose to gastrointestinal ulceration
- No treatment with any investigational drug within the past 30 days
- No major surgical procedure or open biopsy within the past 28 days or anticipated need for a major surgical procedure during the course of the study
Trial locations and contacts
1 site in 1 country.
Italy1 site, 1 recruiting
- Recruiting
Southern Italy Cooperative Oncology Group
Naples, 80131
Pasquale Comella, MD, 39-81-590-3227, pasqualecomella@libero.it
About this study
Official title: Maintenance and Reinduction Chemotherapy With Avastin in Metastatic Colon Cancer: The MARTHA (SICOG 0803) Trial
RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bevacizumab together with combination chemotherapy may kill more tumor cells.
PURPOSE: This phase III trial is studying how well giving induction therapy with bevacizumab together with combination chemotherapy with or without capecitabine followed by bevacizumab maintenance therapy in treating patients with metastatic colorectal cancer that cannot be removed by surgery.
Read the detailed description
OBJECTIVES:
Primary
- To compare two strategies of induction bio-chemotherapy followed by the same maintenance biotherapy in terms of time to failure in patients with previously untreated metastatic colorectal cancer.
Secondary
- To compare the two arms of treatment in terms of response rate, duration of responses, progression-free survival, safety, and quality of life of these patients.
OUTLINE: This is a multicenter study. Patients are stratified according to treatment center, performance status (0 vs 1), and number of metastatic sites (1 vs ≥ 2). Patients are randomized to 1 of 2 induction therapy arms.
- Arm I: Patients receive bevacizumab IV over 30-90 minutes on day 1. Patients also receive FOLFIRI chemotherapy comprising irinotecan hydrochloride IV over 1 hour and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously over 46 hours on days 1 and 2. Treatment repeats every 2 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.
- Arm II: Patients receive bevacizumab and FOLFIRI chemotherapy (B-FOLFIRI) as in arm I. Treatment repeats every 2 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive bevacizumab IV over 30-90 minutes on day 1 and oral capecitabine once every 12 hours on days 1-14. Treatment repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
In both arms, patients achieving stable disease after completion of 6 months of induction therapy proceed to maintenance therapy.
- Maintenance therapy: Patients receive bevacizumab IV over 30-90 minutes every 3 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity.
During or after completion of maintenance therapy, patients with tumor regrowth that is not classified as disease progression from baseline and who achieved partial or complete response during or after their induction therapy proceed to reinduction therapy.
- Reinduction therapy: Patients receive B-FOLFIRI as described previously. Quality of life is assessed at baseline, every 3 months during induction therapy, and at discontinuation of study therapy.
After completion of study therapy, patients are followed for up to 2 years.
- Conditions
- Colorectal Cancer
- Being tested
- bevacizumab, capecitabine, fluorouracil, irinotecan hydrochloride, leucovorin calcium
- Keywords
- stage IV colon cancer, stage IV rectal cancer
- Medical subject headings
- Colorectal Neoplasms, Colonic Neoplasms, Rectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bevacizumabBiological
Given IV
capecitabineDrug
Given orally
fluorouracilDrug
Given IV
Given IV
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Arm I | Active comparator | Patients receive bevacizumab IV over 30-90 minutes on day 1. Patients also receive FOLFIRI chemotherapy comprising irinotecan hydrochloride IV over 1 hour and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously over 46 hours on days 1 and 2. Treatment repeats every 2 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity. Receives: Biological: bevacizumab; Drug: fluorouracil; Drug: irinotecan hydrochloride; Drug: leucovorin calcium |
| Arm II | Experimental | Patients receive bevacizumab and FOLFIRI chemotherapy (B-FOLFIRI) as in arm I. Treatment repeats every 2 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive bevacizumab IV over 30-90 minutes on day 1 and oral capecitabine once every 12 hours on days 1-14. Treatment repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity. Receives: Biological: bevacizumab; Drug: capecitabine; Drug: fluorouracil; Drug: irinotecan hydrochloride; Drug: leucovorin calcium |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to failure of strategy
Secondary outcomes (5)
Response according to RECIST criteria
Duration of response
Progression-free survival
Safety according to NCI CTCAE v3.0
Quality of life as assessed by EORTC QLQ-C30 questionnaire (v 3.0) at baseline, every 3 months during induction chemotherapy, and at discontinuation of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Nov 2008 (estimated)
- Study startJul 2008
- Primary completionJul 2011 (estimated)
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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Masking
- None (open label)
- Enrolment
- 672 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Southern Italy Cooperative Oncology Group
- Sponsor type
- University, hospital or other
- Investigators
- Pasquale Comella, MD, Principal investigator, Istituto Nazionale per lo Studio e la Cura dei Tumori
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00797485
- Sponsor's protocol ID
- CDR0000617983
- Other IDs
- SICOG-0803, EudraCT-2008-004890-17
- Status last verified
- Jun 2009
- First submitted
- 22 Nov 2008
- Last updated
- 26 Aug 2013
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Aug 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Maintenance and Reinduction Chemotherapy With Avastin in Metastatic Colon Cancer: The MARTHA (SICOG 0803) Trial
- ClinicalTrials.gov ID
- NCT00797485
- Acronym / sponsor ID
- CDR0000617983
- Conditions
- Colorectal Cancer
- Keywords
- stage IV colon cancer, stage IV rectal cancer
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 672 participants (estimated)
- Lead sponsor
- Southern Italy Cooperative Oncology GroupUniversity, hospital or other
- Study start
- Jul 2008
- Primary completion
- Jul 2011 (estimated)
- First posted
- 25 Nov 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.
RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bevacizumab together with combination chemotherapy may kill more tumor cells.
PURPOSE: This phase III trial is studying how well giving induction therapy with bevacizumab together with combination chemotherapy with or without capecitabine followed by bevacizumab maintenance therapy in treating patients with metastatic colorectal cancer that cannot be removed by surgery.
Detailed description
OBJECTIVES:
Primary
- To compare two strategies of induction bio-chemotherapy followed by the same maintenance biotherapy in terms of time to failure in patients with previously untreated metastatic colorectal cancer.
Secondary
- To compare the two arms of treatment in terms of response rate, duration of responses, progression-free survival, safety, and quality of life of these patients.
OUTLINE: This is a multicenter study. Patients are stratified according to treatment center, performance status (0 vs 1), and number of metastatic sites (1 vs ≥ 2). Patients are randomized to 1 of 2 induction therapy arms.
- Arm I: Patients receive bevacizumab IV over 30-90 minutes on day 1. Patients also receive FOLFIRI chemotherapy comprising irinotecan hydrochloride IV over 1 hour and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously over 46 hours on days 1 and 2. Treatment repeats every 2 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.
- Arm II: Patients receive bevacizumab and FOLFIRI chemotherapy (B-FOLFIRI) as in arm I. Treatment repeats every 2 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive bevacizumab IV over 30-90 minutes on day 1 and oral capecitabine once every 12 hours on days 1-14. Treatment repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity.
In both arms, patients achieving stable disease after completion of 6 months of induction therapy proceed to maintenance therapy.
- Maintenance therapy: Patients receive bevacizumab IV over 30-90 minutes every 3 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity.
During or after completion of maintenance therapy, patients with tumor regrowth that is not classified as disease progression from baseline and who achieved partial or complete response during or after their induction therapy proceed to reinduction therapy.
- Reinduction therapy: Patients receive B-FOLFIRI as described previously. Quality of life is assessed at baseline, every 3 months during induction therapy, and at discontinuation of study therapy.
After completion of study therapy, patients are followed for up to 2 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I | Active comparator | Biological: bevacizumab, Drug: fluorouracil, Drug: irinotecan hydrochloride, Drug: leucovorin calciumPatients receive bevacizumab IV over 30-90 minutes on day 1. Patients also receive FOLFIRI chemotherapy comprising irinotecan hydrochloride IV over 1 hour and leucovorin calcium IV over 2 hours on day 1 and fluorouracil IV continuously over 46 hours on days 1 and 2. Treatment repeats every 2 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity. |
| Arm II | Experimental | Biological: bevacizumab, Drug: capecitabine, Drug: fluorouracil, Drug: irinotecan hydrochloride, Drug: leucovorin calciumPatients receive bevacizumab and FOLFIRI chemotherapy (B-FOLFIRI) as in arm I. Treatment repeats every 2 weeks for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients then receive bevacizumab IV over 30-90 minutes on day 1 and oral capecitabine once every 12 hours on days 1-14. Treatment repeats every 3 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| bevacizumabGiven IV | Biological | Arm I, Arm II |
| capecitabineGiven orally | Drug | Arm II |
| fluorouracilGiven IV | Drug | Arm I, Arm II |
| irinotecan hydrochlorideGiven IV | Drug | Arm I, Arm II |
| leucovorin calciumGiven IV | Drug | Arm I, Arm II |
Primary outcome
Time to failure of strategy
5 secondary outcomes
Response according to RECIST criteria
Duration of response
Progression-free survival
Safety according to NCI CTCAE v3.0
Quality of life as assessed by EORTC QLQ-C30 questionnaire (v 3.0) at baseline, every 3 months during induction chemotherapy, and at discontinuation of treatment
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Aug 2013.
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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.
Pasquale Comella, MD principal investigator
Istituto Nazionale per lo Studio e la Cura dei Tumori
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing bevacizumab, capecitabine and fluorouracil in people with Colorectal Cancer, run by Southern Italy Cooperative Oncology Group at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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: status not confirmed, as of the sponsor's last update on 26 Aug 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to failure of strategy. 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 26 Aug 2013.