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Trial record 11 of 317 for:    colon cancer | ( Map: Canada )

Phase I Trial of Sorafenib + FOLFIRI In Metastatic Colorectal Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00780169
Recruitment Status : Completed
First Posted : October 27, 2008
Last Update Posted : May 13, 2013
Information provided by (Responsible Party):
Ottawa Hospital Research Institute

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.

Condition or disease Intervention/treatment Phase
Metastatic Colorectal Cancer Drug: sorafenib + FOLFIRI Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 16 participants
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : October 2008
Actual Primary Completion Date : May 2011
Actual Study Completion Date : December 2012

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. 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 :
  1. Pharmacokinetics of Irinotecan in the presence of Sorafenib [ Time Frame: 2 years ]
  2. Response according to Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: every 2 cycles - 8 weeks ]
  3. Time to Progression and Overall Survival [ Time Frame: each cycle - 4 weeks ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00780169

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

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Responsible Party: Ottawa Hospital Research Institute Identifier: NCT00780169     History of Changes
Other Study ID Numbers: OTT 06-08
First Posted: October 27, 2008    Key Record Dates
Last Update Posted: May 13, 2013
Last Verified: May 2013
Additional relevant MeSH terms:
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Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Colonic Diseases
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Rectal Diseases
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action