Metastatic Colorectal CancerPhase 1NCT00780169
Phase I Trial of Sorafenib + FOLFIRI In Metastatic Colorectal Cancer
A Phase 1 study testing sorafenib + FOLFIRI in people with Metastatic Colorectal Cancer, run by Ottawa Hospital Research Institute at 1 site in Canada.
Trial summary
The purpose of this study is to assess the safety, the maximum tolerated dose and the recommended dose for phase II studies of a chemotherapy-combination of sorafenib, irinotecan, and 5-fluorouracil (5-FU)/folinic acid (FA) (FOLFIRI) as first-line treatment for metastatic colorectal cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Colorectal Cancer
- What is being tested?
- sorafenib + FOLFIRI
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteCanada
- Study dates
- Oct 2008to Dec 2012
- 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
Who may be able to join
- Metastatic colorectal cancer
- Histopathological verification of the primary tumor
- Measurable disease according to RESIST criteria
- Response Evaluation Criteria in Solid Tumors (ECOG) performance status ≤ 2
- Age > 18 years.
- Women of childbearing potential must have had a negative pregnancy test within 7 days prior to start of treatment. Women of childbearing potential and men must agree to use adequate contraception prior to study entry and for the duration of study participation.
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- Patients may have had prior adjuvant chemotherapy with fluoropyrimidines WITHOUT pelvic radiotherapy.
- Radiation: Patients may have had prior palliative radiation therapy to NO more than 50% of the areas bearing of bone marrow stores.
- Adequate organ and marrow function : Hemoglobin > 9.0 g/dl; absolute neutrophil count (ANC) >1,500/mm3; absolute granulocyte count(AGC) > 1.5 x 109 /L; Platelets > 100 x 109 /L; Serum creatinine and creatinine clearance within upper normal limit; Bilirubin < 1.0 x upper normal limit, < 2.5 x upper normal limit if documented liver metastases; aspartate aminotransferase (AST) < 2.5 x upper normal limit, < 5 x upper normal limit if documented liver metastases
- Life expectancy > 3 months
- Informed consent
Who cannot join
- Previous or concurrent malignancies
- Patients with central nervous system (CNS) metastases
- Pregnant or lactating women
- Concurrent treatment with other experimental drugs or anticancer therapy
- Previous chemotherapy for advanced and/or metastatic disease
- Previous adjuvant therapy with irinotecan or targeted agents
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- Previous Sorafenib therapy
- Previous full dose curative pelvic radiotherapy
- History of cardiovascular disease, cerebral ischemia infarction or hemorrhage, Gilbert's disease, HIV positivity
- Unable to be compliant with the procedures in the protocol
- Currently use prohibited medications
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I Study of Sorafenib (Nexavar®) in Combination With FOLFIRI as First Line Therapy for Metastatic Colorectal Cancer
The purpose of this study is to assess the safety, the maximum tolerated dose and the recommended dose for phase II studies of a chemotherapy-combination of sorafenib, irinotecan, and 5-fluorouracil (5-FU)/folinic acid (FA) (FOLFIRI) as first-line treatment for metastatic colorectal cancer.
Read the detailed description
A standard phase I dose escalation design with three to six patients per dose level will be used. The first three patients will receive chemotherapy at the dose level 1 for 4 weeks (2 FOLFIRI regimen). The dose will be escalated for the next patients by one dose level if none of the three patients at a dose level experience a dose-limiting toxicity (DLT) during the first six weeks. Intrapatient dose escalation is not allowed. If one of the three patients has a DLT, an additional three patients will be enrolled at this dose level and the dose will be escalated if no additional patients experience a DLT. Otherwise, the dose escalation will be stopped, and the last dose will be regarded as the Maximum Administered Dose (MAD). The preceding dose level will be declared the Maximum Tolerated Dose (MTD). This dose level will be the recommended dose (RD). At least 6 patients will be treated at the MTD. The cohort at the MTD dose level can be expanded to as many as 12 patients to gain experience with the toxicities and efficacy of Sorafenib + FOLFIRI combination over a broad patient range. Patients experiencing a DLT during the first cycle of treatment will have the drug withheld. They will be eligible for repeated treatment at a lower dose or treated off protocol.
Treatment is to be discontinued in cases of serious or unmanageable toxicity or request by the patient. Otherwise therapy will continue until clinically or radiologically documented disease progression.
- Conditions
- Metastatic Colorectal Cancer
- Being tested
- sorafenib + FOLFIRI
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
sorafenib + FOLFIRIDrug
Also called sorafenib - Nexavar
escalating doses of sorafenib and irinotecan
- sorafenib starting dose 400 mg/day
- irinotecan starting dose 80 mg/m2 on day 1
| Study group | Role | What they receive |
|---|---|---|
| sorafenib +FOLFIRI | Experimental | This is a Phase I safety study. There is only one arm of FOLFIRI administered every 14 days (2 week schedule) and sorafenib administered orally, twice daily continuously. First cycle sorafenib began at day +2 to FOLFIRI. Receives: Drug: sorafenib + FOLFIRI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Toxicity spectrum of Sorafenib (MTD, DLT) and the recommended dose (RD) for phase II studies of Sorafenib when combined with FOLFIRI in first line patients with metastatic colorectal cancer (mCRC)
Measured: each cycle - 4 weeks; continuous monitoring of AEs
Secondary outcomes (3)
Pharmacokinetics of Irinotecan in the presence of Sorafenib
Measured: 2 years
Response according to Response Evaluation Criteria in Solid Tumors (RECIST)
Measured: every 2 cycles - 8 weeks
Time to Progression and Overall Survival
Measured: each cycle - 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Oct 2008 (estimated)
- Study startOct 2008
- Primary completionMay 2011
- Study completionDec 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Colorectal CancerStudies of the same condition, open and under way.
- More trials run by Ottawa Hospital Research InstituteThe 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
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ottawa Hospital Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Bayer
- Responsible party
- Sponsor
- Investigators
- Jean A Maroun, MD, Principal investigator, The Ottawa Hospital Regional Cancer Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00780169
- Sponsor's protocol ID
- OTT 06-08
- Status last verified
- May 2013
- First submitted
- 23 Oct 2008
- Last updated
- 13 May 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of Sorafenib (Nexavar®) in Combination With FOLFIRI as First Line Therapy for Metastatic Colorectal Cancer
- ClinicalTrials.gov ID
- NCT00780169
- Acronym / sponsor ID
- OTT 06-08
- Conditions
- Metastatic Colorectal Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- Ottawa Hospital Research InstituteUniversity, hospital or other
- Collaborators
- Bayer
- Study start
- Oct 2008
- Primary completion
- May 2011 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 27 Oct 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 purpose of this study is to assess the safety, the maximum tolerated dose and the recommended dose for phase II studies of a chemotherapy-combination of sorafenib, irinotecan, and 5-fluorouracil (5-FU)/folinic acid (FA) (FOLFIRI) as first-line treatment for metastatic colorectal cancer.
Detailed description
A standard phase I dose escalation design with three to six patients per dose level will be used. The first three patients will receive chemotherapy at the dose level 1 for 4 weeks (2 FOLFIRI regimen). The dose will be escalated for the next patients by one dose level if none of the three patients at a dose level experience a dose-limiting toxicity (DLT) during the first six weeks. Intrapatient dose escalation is not allowed. If one of the three patients has a DLT, an additional three patients will be enrolled at this dose level and the dose will be escalated if no additional patients experience a DLT. Otherwise, the dose escalation will be stopped, and the last dose will be regarded as the Maximum Administered Dose (MAD). The preceding dose level will be declared the Maximum Tolerated Dose (MTD). This dose level will be the recommended dose (RD). At least 6 patients will be treated at the MTD. The cohort at the MTD dose level can be expanded to as many as 12 patients to gain experience with the toxicities and efficacy of Sorafenib + FOLFIRI combination over a broad patient range. Patients experiencing a DLT during the first cycle of treatment will have the drug withheld. They will be eligible for repeated treatment at a lower dose or treated off protocol.
Treatment is to be discontinued in cases of serious or unmanageable toxicity or request by the patient. Otherwise therapy will continue until clinically or radiologically documented disease progression.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| sorafenib +FOLFIRI | Experimental | Drug: sorafenib + FOLFIRIThis is a Phase I safety study. There is only one arm of FOLFIRI administered every 14 days (2 week schedule) and sorafenib administered orally, twice daily continuously. First cycle sorafenib began at day +2 to FOLFIRI. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Metastatic colorectal cancer
- Histopathological verification of the primary tumor
- Measurable disease according to RESIST criteria
- Response Evaluation Criteria in Solid Tumors (ECOG) performance status ≤ 2
- Age > 18 years.
Key exclusion criteria (11 listed)
- Previous or concurrent malignancies
- Patients with central nervous system (CNS) metastases
- Pregnant or lactating women
- Concurrent treatment with other experimental drugs or anticancer therapy
- Previous chemotherapy for advanced and/or metastatic disease
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 |
|---|---|---|
| sorafenib + FOLFIRIAlso: sorafenib - Nexavarescalating doses of sorafenib and irinotecan * sorafenib starting dose 400 mg/day * irinotecan starting dose 80 mg/m2 on day 1 | Drug | sorafenib +FOLFIRI |
Primary outcome
Toxicity spectrum of Sorafenib (MTD, DLT) and the recommended dose (RD) for phase II studies of Sorafenib when combined with FOLFIRI in first line patients with metastatic colorectal cancer (mCRC)
Time frame: each cycle - 4 weeks; continuous monitoring of AEs
3 secondary outcomes
Pharmacokinetics of Irinotecan in the presence of Sorafenib
Time frame: 2 years
Response according to Response Evaluation Criteria in Solid Tumors (RECIST)
Time frame: every 2 cycles - 8 weeks
Time to Progression and Overall Survival
Time frame: each cycle - 4 weeks
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 13 May 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.
Jean A Maroun, MD principal investigator
The Ottawa Hospital Regional Cancer Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing sorafenib + FOLFIRI in people with Metastatic Colorectal Cancer, run by Ottawa Hospital Research Institute at 1 site in Canada.
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 11 inclusion and 11 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: finished, as of the sponsor's last update on 13 May 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 Canada. 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?
Toxicity spectrum of Sorafenib (MTD, DLT) and the recommended dose (RD) for phase II studies of Sorafenib when combined with FOLFIRI in first line patients with metastatic colorectal cancer (mCRC) (time frame: each cycle - 4 weeks; continuous monitoring of AEs). 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 13 May 2013.