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Phase I Trial of Sorafenib + FOLFIRI In Metastatic Colorectal Cancer

This study has been completed.
Information provided by (Responsible Party):
Ottawa Hospital Research Institute Identifier:
First received: October 23, 2008
Last updated: May 9, 2013
Last verified: May 2013
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.

Condition Intervention Phase
Metastatic Colorectal Cancer
Drug: sorafenib + FOLFIRI
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of Sorafenib (Nexavar®) in Combination With FOLFIRI as First Line Therapy for Metastatic Colorectal Cancer

Resource links provided by NLM:

Further study details as provided by Ottawa Hospital Research Institute:

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) [ Time Frame: each cycle - 4 weeks; continuous monitoring of AEs ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 16
Study Start Date: October 2008
Study Completion Date: December 2012
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: sorafenib +FOLFIRI
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.
Drug: sorafenib + FOLFIRI

escalating doses of sorafenib and irinotecan

  • sorafenib starting dose 400 mg/day
  • irinotecan starting dose 80 mg/m2 on day 1
Other Name: sorafenib - Nexavar

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.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00780169

Canada, Ontario
The Ottawa Hospital Cancer Centre
Ottawa, Ontario, Canada, K1H 8L6
Sponsors and Collaborators
Ottawa Hospital Research Institute
Principal Investigator: Jean A Maroun, MD The Ottawa Hospital Regional Cancer Centre
  More Information

Responsible Party: Ottawa Hospital Research Institute Identifier: NCT00780169     History of Changes
Other Study ID Numbers: OTT 06-08
Study First Received: October 23, 2008
Last Updated: May 9, 2013

Additional relevant MeSH terms:
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Vitamin B Complex
Growth Substances
Physiological Effects of Drugs processed this record on March 28, 2017