Phase I Trial of Sorafenib + FOLFIRI In Metastatic Colorectal Cancer
Primary Purpose
Metastatic Colorectal Cancer
Status
Completed
Phase
Phase 1
Locations
Canada
Study Type
Interventional
Intervention
sorafenib + FOLFIRI
Sponsored by
About this trial
This is an interventional treatment trial for Metastatic Colorectal Cancer
Eligibility Criteria
Inclusion Criteria:
- 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.
- 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
Exclusion Criteria:
- 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
- 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
Sites / Locations
- The Ottawa Hospital Cancer Centre
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
sorafenib +FOLFIRI
Arm Description
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.
Outcomes
Primary Outcome Measures
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)
Secondary Outcome Measures
Pharmacokinetics of Irinotecan in the presence of Sorafenib
Response according to Response Evaluation Criteria in Solid Tumors (RECIST)
Time to Progression and Overall Survival
Full Information
NCT ID
NCT00780169
First Posted
October 23, 2008
Last Updated
May 9, 2013
Sponsor
Ottawa Hospital Research Institute
Collaborators
Bayer
1. Study Identification
Unique Protocol Identification Number
NCT00780169
Brief Title
Phase I Trial of Sorafenib + FOLFIRI In Metastatic Colorectal Cancer
Official Title
A Phase I Study of Sorafenib (Nexavar®) in Combination With FOLFIRI as First Line Therapy for Metastatic Colorectal Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
May 2013
Overall Recruitment Status
Completed
Study Start Date
October 2008 (undefined)
Primary Completion Date
May 2011 (Actual)
Study Completion Date
December 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Ottawa Hospital Research Institute
Collaborators
Bayer
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Colorectal Cancer
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
16 (Actual)
8. Arms, Groups, and Interventions
Arm Title
sorafenib +FOLFIRI
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
sorafenib + FOLFIRI
Other Intervention Name(s)
sorafenib - Nexavar
Intervention Description
escalating doses of sorafenib and irinotecan
sorafenib starting dose 400 mg/day
irinotecan starting dose 80 mg/m2 on day 1
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
Pharmacokinetics of Irinotecan in the presence of Sorafenib
Time Frame
2 years
Title
Response according to Response Evaluation Criteria in Solid Tumors (RECIST)
Time Frame
every 2 cycles - 8 weeks
Title
Time to Progression and Overall Survival
Time Frame
each cycle - 4 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
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
Exclusion Criteria:
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
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jean A Maroun, MD
Organizational Affiliation
The Ottawa Hospital Regional Cancer Centre
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Ottawa Hospital Cancer Centre
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1H 8L6
Country
Canada
12. IPD Sharing Statement
Learn more about this trial
Phase I Trial of Sorafenib + FOLFIRI In Metastatic Colorectal Cancer
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