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A Phase I Study of Sorafenib (Nexavar®) in Combination With FOLFIRI as First Line Therapy for Metastatic Colorectal Cancer

Phase 1
18 Years
Not Enrolling
Metastatic Colorectal Cancer

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Trial Information

A Phase I Study of Sorafenib (Nexavar®) in Combination With FOLFIRI as First Line Therapy for Metastatic Colorectal Cancer

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

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.

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

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

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)

Outcome Time Frame:

each cycle - 4 weeks; continuous monitoring of AEs

Safety Issue:


Principal Investigator

Jean A Maroun, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

The Ottawa Hospital Regional Cancer Centre


Canada: Health Canada

Study ID:

OTT 06-08



Start Date:

October 2008

Completion Date:

December 2012

Related Keywords:

  • Metastatic Colorectal Cancer
  • Colorectal Neoplasms