Phase I Trial of Sorafenib + FOLFIRI In Metastatic Colorectal Cancer - Full Text View

Sponsors and Collaborators:	Ottawa Health Research Institute Bayer
Information provided by:	Ottawa Health Research Institute
ClinicalTrials.gov Identifier:	NCT00780169

Purpose

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 I

MedlinePlus related topics: Cancer Colorectal Cancer

Drug Information available for: Irinotecan Irinotecan hydrochloride Sorafenib Sorafenib tosylate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety Study
Official Title:	A Phase I Study of Sorafenib (Nexavar®) in Combination With FOLFIRI as First Line Therapy for Metastatic Colorectal Cancer

Further study details as provided by Ottawa Health 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 mCRC [ Time Frame: each cycle - 4 weeks; continuous monitoring of AEs ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Pharmacokinetics of Irinotecan in the presence of Sorafenib [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
Response according to RECIST criteria [ Time Frame: every 2 cycles - 8 weeks ] [ Designated as safety issue: No ]
Time to Progression and Overall Survival [ Time Frame: each cycle - 4 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment:	30
Study Start Date:	October 2008
Estimated Study Completion Date:	April 2011
Estimated Primary Completion Date:	October 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental This is a Phase I safety study. There is only one arm	Drug: sorafenib + FOLFIRI escalating doses of sorafenib and irinotecan sorafenib starting dose 400 mg/day irinotecan starting dose 80 mg/m2 on day 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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Metastatic colorectal cancer
Histopathological verification of the primary tumor
Measurable disease according to RESIST criteria
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; ANC >1,500/mm3; 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; 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 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

Please refer to this study by its ClinicalTrials.gov identifier: NCT00780169

Contacts

Contact: Jean A Maroun, MD	(613) 737 7700 ext 70181	jmaroun@Ottawahospital.on.ca
Contact: Derek Jonker, MD	613 737 7700 ext 70168	djonker@ottawahospital.on.ca

Locations

Canada, Ontario
The Ottawa Hospital Regional Cancer Centre	Recruiting
Ottawa, Ontario, Canada, K1H 8L6

Sponsors and Collaborators

Ottawa Health Research Institute

Bayer

Investigators

Principal Investigator:

Jean A Maroun, MD

The Ottawa Hospital Regional Cancer Centre

More Information

Responsible Party:	Ottawa Health Research Institute ( Jean A. Maroun )
Study ID Numbers:	OTT 06-08
Study First Received:	October 23, 2008
Last Updated:	October 23, 2008
ClinicalTrials.gov Identifier:	NCT00780169
Health Authority:	Canada: Health Canada

Study placed in the following topic categories:

Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Irinotecan
Colonic Diseases
Gastrointestinal Neoplasms

Intestinal Diseases
Sorafenib
Rectal Diseases
Intestinal Neoplasms
Colorectal Neoplasms

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Site
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents

Therapeutic Uses
Enzyme Inhibitors
Protein Kinase Inhibitors
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009