Phase I Trial of Sorafenib + FOLFIRI In Metastatic Colorectal Cancer
Information source: Ottawa Hospital Research Institute
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Metastatic Colorectal Cancer
Intervention: sorafenib + FOLFIRI (Drug)
Phase: Phase 1
Status: Completed
Sponsored by: Ottawa Hospital Research Institute Official(s) and/or principal investigator(s): Jean A Maroun, MD, Principal Investigator, Affiliation: The Ottawa Hospital Regional Cancer Centre
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.
Clinical Details
Official title: A Phase I Study of Sorafenib (Nexavar®) in Combination With FOLFIRI as First Line Therapy for Metastatic Colorectal Cancer
Study design: Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
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)
Secondary outcome: Pharmacokinetics of Irinotecan in the presence of SorafenibResponse according to Response Evaluation Criteria in Solid Tumors (RECIST) Time to Progression and Overall Survival
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.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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
Locations and Contacts
The Ottawa Hospital Cancer Centre, Ottawa, Ontario K1H 8L6, Canada
Additional Information
Starting date: October 2008
Last updated: May 9, 2013
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