Colorectal CancerPhase 1NCT00118261
Erlotinib, Modified FOLFOX6, and Bevacizumab as First-Line Therapy Metastatic Colorectal Cancer
A Phase 1 study testing bevacizumab, erlotinib hydrochloride and fluorouracil in people with Colorectal Cancer, run by Case Comprehensive Cancer Center at 3 sites in United States.
Trial summary
RATIONALE: Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as oxaliplatin, leucovorin, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- bevacizumab, erlotinib hydrochloride 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
- 17 participants
- Where
- 3 sitesUnited States
- Study dates
- Mar 2005to Jan 2011
- Phase
- Phase 1
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS:
- Histologically confirmed colorectal cancer
- Biopsy-accessible metastatic disease
- Measurable disease
- No CNS metastases
PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- ECOG 0-2
Life expectancy
- At least 3 months
Hematopoietic
- WBC ≥ 4,000/mm^3 OR
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Hemoglobin ≥ 10 g/dL
- No bleeding disorder
Hepatic
- Bilirubin ≤ 1.5 mg/dL
- Albumin ≥ 2.5 g/dL
Renal
- Creatinine ≤ 1.5 mg/dL
- Urine protein:creatine ratio < 1.0
Cardiovascular
- Blood pressure ≤ 150/100 mmHg
- No arterial thrombotic event within the past 6 months
- No New York Heart Association grade II-IV congestive heart failure
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 1 month after completion of study treatment
- No other malignancy within the past 3 years except nonmelanoma skin cancer, carcinoma in situ of the cervix, or other malignancy with < 10% chance of relapse within 3 years
- No uncontrolled infection
- No severe uncontrolled illness that would preclude study participation
- No peripheral neuropathy interfering with function
- No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
- No serious non-healing wound, ulcer, or bone fracture
PRIOR CONCURRENT THERAPY:
Biologic therapy
- No concurrent immunotherapy
- No concurrent sargramostim (GM-CSF)
Chemotherapy
- No prior chemotherapy, including oxaliplatin, for metastatic disease
- Prior adjuvant oxaliplatin allowed provided disease progressed > 12 months after completion of oxaliplatin
- At least 3 weeks since prior cytotoxic chemotherapy (6 weeks for mitomycin or nitrosoureas)
- No more than 2 courses of prior mitomycin
- No concurrent chemotherapy
Endocrine therapy
- No concurrent anticancer hormonal therapy
Radiotherapy
- At least 2 weeks since prior radiotherapy
- No prior radiotherapy to > 15% of bone marrow
- No concurrent radiotherapy
Surgery
- At least 4 weeks since prior major surgery
- At least 1 week since prior minor surgery
Other
- Recovered from prior therapy
- No prior epidermal growth factor receptor inhibitor therapy
- No other concurrent antineoplastic or antitumor therapy
- No other concurrent investigational agents
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
Cleveland, Ohio, 44106-5065
MetroHealth Cancer Care Center at MetroHealth Medical Center
Cleveland, Ohio, 44109
UHHS Chagrin Highlands Medical Center
Cleveland, Ohio, 44122
About this study
Official title: A Phase IB Study in Patients With Metastatic Colorectal Cancer to Evaluate Pharmacodynamic Effects of Erlotinib and Safety and Efficacy of Erlotinib in Combination With Modified FOLFOX6 (mFOLFOX6) and Bevacizumab
RATIONALE: Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as oxaliplatin, leucovorin, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. 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. Erlotinib may help chemotherapy work better by making tumor cells more sensitive to the drugs. Giving erlotinib together with combination chemotherapy and bevacizumab may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of erlotinib when given together with combination chemotherapy and bevacizumab as first-line therapy in treating patients with metastatic colorectal cancer.
Read the detailed description
OBJECTIVES:
- Determine the toxicity of erlotinib, mFOLFOX6, and bevacizumab in patients with metastatic colorectal cancer.
- Determine the efficacy of this regimen in these patients.
- Determine the feasibility of escalating the dose of erlotinib in order to maximize the likelihood of developing a grade 2 skin rash in select patients.
OUTLINE: This is a multicenter study.
- Single-agent erlotinib: Patients receive oral erlotinib once daily on days 1-14 (course 1).
- Erlotinib, modified FOLFOX6, and bevacizumab chemotherapy: Patients receive oral erlotinib* once daily on days 1-14, oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1, and fluorouracil IV continuously over 46 hours on days 1 and 2 in course 2. Beginning in course 3, patients also receive bevacizumab IV over 30 minutes. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
NOTE: Patients who do not develop grade 2 toxicity after the first 3 courses (6 weeks) will have their erlotinib dose escalated.
PROJECTED ACCRUAL: A total of 22 patients will be accrued for this study.
- Conditions
- Colorectal Cancer
- Being tested
- bevacizumab, erlotinib hydrochloride, fluorouracil, leucovorin calcium, oxaliplatin
- Keywords
- stage IV rectal cancer, stage IV colon cancer, recurrent rectal cancer, recurrent colon cancer
- Medical subject headings
- Colorectal Neoplasms, Rectal Neoplasms, Colonic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bevacizumabBiological
Beginning in course 3, patients also receive bevacizumab IV over 30 minutes. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
erlotinib hydrochlorideDrug
Courses 1-3: oral erlotinib once daily on days 1-14. Patients who do not develop grade 2 toxicity after the first 3 courses (6 weeks) will have their erlotinib dose escalated. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
fluorouracilDrug
Starting with course 2: fluorouracil IV continuously over 46 hours on days 1 and 2. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Starting with course 2: Leucovorin calcium IV over 2 hours on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
oxaliplatinDrug
Starting with course 2: oxaliplatin IV over 2 hours on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
| Study group | Role | What they receive |
|---|---|---|
| Erlotinib, modified FOLFOX6, and bevacizumab | Experimental | Not described Receives: Biological: bevacizumab; Drug: erlotinib hydrochloride; Drug: fluorouracil; Drug: leucovorin calcium; Drug: oxaliplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients that develop study drug related toxicity
Dose-limiting toxicities will be tracked in the first three cycles. The occurrence of DLT in 2 of the first 6 patients, 3 of the first 9 patients, or 4 of the first 12 patients (whichever occurs soonest)will require that subsequent patients are enrolled to the study at 100 mg erlotinib daily.
Measured: 3 courses (6 weeks)
Secondary outcomes (2)
Patient Response to Treatment Measured by RECIST Criteria
The overall response is the number of participants who experience a confirmed complete (CR) or partial response (PR) of the total analysis population. Per the Response Evaluation Criteria In Solid Tumors (RECIST): CR = all detectable tumor has disappeared, PR = a >=30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum, Progressive disease (PD) = a >=20% increase in target lesions, Stable Disease = small changes that do not meet previously given criteria.
Measured: 3 courses (6 weeks)
Number of patients that can increase the erlotinib dose to 200mg
The number of patients requiring an increase in erlotinib dose to 200 mg will be reported as well as the toxicities observed at 200 mg daily erlotinib, the median onset to grade 2 or higher rash and diarrhea at 200 mg erlotinib, and the number of patients requiring a decrease in erlotinib from 200 mg.
Measured: 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2005 (estimated)
- Study startMar 2005
- Primary completionJan 2011
- Study completionJan 2011
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.
- More trials run by Case Comprehensive Cancer CenterThe 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Case Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Smitha Krishnamurthi, Case Comprehensive Cancer Center
- Investigators
- Smitha Krishnamurthi, MD, Principal investigator, Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00118261
- Sponsor's protocol ID
- CASE2204
- Other IDs
- P30CA043703, CASE2204, NCI-2009-01287
- Status last verified
- Aug 2012
- First submitted
- 8 Jul 2005
- Last updated
- 3 Sep 2012
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 3 Sep 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase IB Study in Patients With Metastatic Colorectal Cancer to Evaluate Pharmacodynamic Effects of Erlotinib and Safety and Efficacy of Erlotinib in Combination With Modified FOLFOX6 (mFOLFOX6) and Bevacizumab
- ClinicalTrials.gov ID
- NCT00118261
- Acronym / sponsor ID
- CASE2204
- Conditions
- Colorectal Cancer
- Keywords
- stage IV rectal cancer, stage IV colon cancer, recurrent rectal cancer, recurrent colon cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Case Comprehensive Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Mar 2005
- Primary completion
- Jan 2011 (actual)
- Study completion
- Jan 2011 (actual)
- First posted
- 11 Jul 2005 (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: Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as oxaliplatin, leucovorin, and fluorouracil, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. 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. Erlotinib may help chemotherapy work better by making tumor cells more sensitive to the drugs. Giving erlotinib together with combination chemotherapy and bevacizumab may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of erlotinib when given together with combination chemotherapy and bevacizumab as first-line therapy in treating patients with metastatic colorectal cancer.
Detailed description
OBJECTIVES:
- Determine the toxicity of erlotinib, mFOLFOX6, and bevacizumab in patients with metastatic colorectal cancer.
- Determine the efficacy of this regimen in these patients.
- Determine the feasibility of escalating the dose of erlotinib in order to maximize the likelihood of developing a grade 2 skin rash in select patients.
OUTLINE: This is a multicenter study.
- Single-agent erlotinib: Patients receive oral erlotinib once daily on days 1-14 (course 1).
- Erlotinib, modified FOLFOX6, and bevacizumab chemotherapy: Patients receive oral erlotinib* once daily on days 1-14, oxaliplatin IV over 2 hours and leucovorin calcium IV over 2 hours on day 1, and fluorouracil IV continuously over 46 hours on days 1 and 2 in course 2. Beginning in course 3, patients also receive bevacizumab IV over 30 minutes. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
NOTE: Patients who do not develop grade 2 toxicity after the first 3 courses (6 weeks) will have their erlotinib dose escalated.
PROJECTED ACCRUAL: A total of 22 patients will be accrued for this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Erlotinib, modified FOLFOX6, and bevacizumab | Experimental | Biological: bevacizumab, Drug: erlotinib hydrochloride, Drug: fluorouracil, Drug: leucovorin calcium, Drug: oxaliplatin |
Who may qualify
- Ages
- 18 years and older
- 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 |
|---|---|---|
| bevacizumabBeginning in course 3, patients also receive bevacizumab IV over 30 minutes. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. | Biological | Erlotinib, modified FOLFOX6, and bevacizumab |
| erlotinib hydrochlorideCourses 1-3: oral erlotinib once daily on days 1-14. Patients who do not develop grade 2 toxicity after the first 3 courses (6 weeks) will have their erlotinib dose escalated. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. | Drug | Erlotinib, modified FOLFOX6, and bevacizumab |
| fluorouracilStarting with course 2: fluorouracil IV continuously over 46 hours on days 1 and 2. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. | Drug | Erlotinib, modified FOLFOX6, and bevacizumab |
| leucovorin calciumStarting with course 2: Leucovorin calcium IV over 2 hours on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. | Drug | Erlotinib, modified FOLFOX6, and bevacizumab |
| oxaliplatinStarting with course 2: oxaliplatin IV over 2 hours on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. | Drug | Erlotinib, modified FOLFOX6, and bevacizumab |
Primary outcome
Number of patients that develop study drug related toxicity
Time frame: 3 courses (6 weeks)
Dose-limiting toxicities will be tracked in the first three cycles. The occurrence of DLT in 2 of the first 6 patients, 3 of the first 9 patients, or 4 of the first 12 patients (whichever occurs soonest)will require that subsequent patients are enrolled to the study at 100 mg erlotinib daily.
2 secondary outcomes
Patient Response to Treatment Measured by RECIST Criteria
Time frame: 3 courses (6 weeks)
Number of patients that can increase the erlotinib dose to 200mg
Time frame: 14 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Sep 2012.
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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.
Smitha Krishnamurthi, MD principal investigator
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing bevacizumab, erlotinib hydrochloride and fluorouracil in people with Colorectal Cancer, run by Case Comprehensive Cancer Center at 3 sites in United States.
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: finished, as of the sponsor's last update on 3 Sep 2012. 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 United States. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Number of patients that develop study drug related toxicity (time frame: 3 courses (6 weeks)). 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 3 Sep 2012.