Phase I Trial of Sorafenib + FOLFIRI In Metastatic Colorectal Cancer

NCT00780169 | Completed Phase 1 DMC

• 1 other identifier: OTT 06-08
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Metastatic Colorectal Cancer

Outcome Measures

Primary Outcomes (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)

  each cycle - 4 weeks; continuous monitoring of AEs

Secondary Outcomes (3)

• Pharmacokinetics of Irinotecan in the presence of Sorafenib

  2 years

• Response according to Response Evaluation Criteria in Solid Tumors (RECIST)

  every 2 cycles - 8 weeks

• Time to Progression and Overall Survival

  each cycle - 4 weeks

Study Arms (1)

sorafenib +FOLFIRI

EXPERIMENTAL

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

Interventions

sorafenib + FOLFIRI DRUG

escalating doses of sorafenib and irinotecan * sorafenib starting dose 400 mg/day * irinotecan starting dose 80 mg/m2 on day 1

Also known as: sorafenib - Nexavar

sorafenib +FOLFIRI

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Ottawa Hospital Research Institute: lead
• Bayer: collaborator

Study Sites (1)

The Ottawa Hospital Cancer Centre

Ottawa, Ontario, K1H 8L6, Canada

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Sorafenib

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Phenylurea Compounds; Urea; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Niacinamide; Nicotinic Acids; Acids, Heterocyclic; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring

Study Officials

• Jean A Maroun, MD

  The Ottawa Hospital Regional Cancer Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 23, 2008
• First Posted: October 27, 2008
• Study Start: October 1, 2008
• Primary Completion: May 1, 2011
• Study Completion: December 1, 2012
• Last Updated: May 13, 2013

Record last verified: 2013-05

Locations

CA (1)