Study to Evaluate the Effects of Sorafenib if Combined With Chemotherapy (FOLFOX6 or FOLFIRI) in the Second-Line Treatment of Colorectal Cancer (FOSCO)

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
AIO-Studien-gGmbH
ClinicalTrials.gov Identifier:
NCT00889343
First received: April 17, 2009
Last updated: March 1, 2013
Last verified: March 2013
  Purpose

The purpose of this study is to determine whether sorafenib in combination with chemotherapy has a positive effect on time to progression of the tumor or death for the treatment of large bowel cancer that has already progressed during a first chemotherapy.


Condition Intervention Phase
Colorectal Neoplasms
Drug: Sorafenib
Drug: Placebo
Drug: Oxaliplatin or Irinotecan
Drug: Leucovorin
Drug: 5-Fluorouracil
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Controlled Randomized Double-blind Multi-center Phase II Study of FOLFOX6 or FOLFIRI Combined With Sorafenib Versus Placebo in Second-line Metastatic Colorectal Carcinoma

Resource links provided by NLM:


Further study details as provided by AIO-Studien-gGmbH:

Primary Outcome Measures:
  • To compare the PFS between patients receiving chemotherapy (FOLFOX6 or FOLFIRI) + sorafenib with chemotherapy + placebo [ Time Frame: 6 to 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Disease control rate [ Time Frame: 6 to 12 months ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: 6 to 12 months ] [ Designated as safety issue: No ]
  • Response rates [ Time Frame: 6 to 12 months ] [ Designated as safety issue: No ]
  • Safety [ Time Frame: signature of informed consent until 30 days after end of treatment ] [ Designated as safety issue: Yes ]

Enrollment: 101
Study Start Date: March 2009
Study Completion Date: December 2012
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: Sorafenib
2x200 mg filmcoated tablets BID on day 2-12 of a 14-days cycle, oral
Other Name: Nexavar
Drug: Oxaliplatin or Irinotecan
Oxaliplatin 100 mg/m2 intravenous infusion on day 1 of 14-days cycle, Irinotecan 180 mg/m2 intravenous infusion on day 1 of 14-days cycle
Drug: Leucovorin
400 mg/m2 intravenous infusion on day 1 of a 14-days cycle
Drug: 5-Fluorouracil
400 mg/m2 intravenous bolus infusion on day 1, 2400 mg/m2 46 hour intravenous infusion on day 1 to 2 of a 14-days cycle
Placebo Comparator: 2 Drug: Placebo
2 filmcoated tablets BID, day 2-12 of a 14-days cycle, oral
Drug: Oxaliplatin or Irinotecan
Oxaliplatin 100 mg/m2 intravenous infusion on day 1 of 14-days cycle, Irinotecan 180 mg/m2 intravenous infusion on day 1 of 14-days cycle
Drug: Leucovorin
400 mg/m2 intravenous infusion on day 1 of a 14-days cycle
Drug: 5-Fluorouracil
400 mg/m2 intravenous bolus infusion on day 1, 2400 mg/m2 46 hour intravenous infusion on day 1 to 2 of a 14-days cycle

Detailed Description:

Patients with metastatic CRC who received a first-line therapy with an Oxaliplatin- or Irinotecan based Fluoropyrimidine containing regimen ± bevacizumab and had a progression subsequently, are eligible for this study. Patients will be randomized to receive chemotherapy (FOLFOX6 or FOLFIRI) + sorafenib 400 mg bid or chemotherapy + placebo. Patients who have received an Oxaliplatin based Fluoropyrimidine containing regimen in first-line will obtain FOLFIRI during this study. Patients who have received an Irinotecan based Fluoropyrimidine containing regimen in first-line will obtain FOLFOX6.

Primary objective of the study is to compare the Progression-free-survival (PFS) between patients receiving chemotherapy (FOLFOX6 or FOLFIRI) + sorafenib with chemotherapy + placebo.

  Eligibility

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

Inclusion Criteria:

  • Age > 18 years.
  • ECOG Performance Status of 0 to 2
  • Life expectancy of at least 12 weeks.
  • Subjects with at least one uni-dimensional (RECIST) measurable lesion of metastatic colorectal carcinoma after first-line chemotherapy with an Oxaliplatin- or Irinotecan based Fluoropyrimidine containing regimen ± bevacizumab and had a progression subsequently. Lesions must be measured by CT-scan or MRI.
  • Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to screening:
  • Hemoglobin > 9.0 g/dl
  • Absolute neutrophil count (ANC) >1,500/mm3
  • Platelet count 100,000/μl Total bilirubin < 1.5 times the upper limit of normal
  • ALT and AST < 2.5 x upper limit of normal (< 5 x upper limit of normal for patients with liver involvement of their cancer)
  • Alkaline phosphatase < 4 x upper limit of normal
  • PT-INR/PTT < 1.5 x upper limit of normal [Patients who are being therapeutically anticoagulated with an agent such as coumadin or heparin will be allowed to participate provided that no prior evidence of underlying abnormality in these parameters exists.]
  • Serum creatinine < 1.5 x upper limit of normal
  • Signed and dated informed consent before the start of specific protocol procedures

Exclusion Criteria:

  • History of cardiac disease: congestive heart failure >NYHA class 2; active CAD (MI more than 6 mo prior to study entry is allowed); cardiac arrythmias requiring anti-arrythmic therapy (beta blockers or digoxin are permitted) or uncontrolled hypertension
  • History of HIV infection or chronic hepatitis B or C
  • Active clinically serious infections (> grade 2 NCI-CTC version 3.0)
  • Symptomatic metastatic brain or meningeal tumors (unless the patient is > 6 months from definitive therapy, has a negative imaging study within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry)
  • Patients with seizure disorder requiring medication (such as steroids or anti-epileptics)
  • History of organ allograft
  • Patients with evidence or history of bleeding diathesis
  • Patients undergoing renal dialysis
  • Known deficit in Dihydropyrimidine Deshydrogenase (DPD)
  • Contraindications for the use of atropine in patients receiving FOLFIRI
  • Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors [Ta, Tis & T1] or any cancer curatively treated > 3 years prior to study entry.
  • Peripheral sensory neuropathy > CTC grade 2
  • Chronic inflammatory bowel disease; ileus; genetic fructose intolerance
  • Pregnant or breast-feeding patients.
  • Women of childbearing potential must have a negative pregnancy test performed within 7 days before the start of treatment. Fertile women and men (<2 years after last menstruation in women) must use effective means of contraception (intrauterine contraceptive device, contraceptive implants, injectables (hormonal depot), transdermal hormonal contraception (contraceptive patch), sexual abstinence or vasectomised partner) during treatment and for at least 6 months after last administration of medication.
  • Substance abuse, medical, psychological or social conditions that may interfere with the patient‟s participation in the study or evaluation of the study results
  • Any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study 18. Patients unable to swallow oral medications.
  • Any other anticancer chemotherapy or immunotherapy during the study or within 4 weeks of study entry.
  • Radiotherapy during study or within 3 weeks of start of study drug. (Palliative radiotherapy will be allowed). Major surgery within 4 weeks of start of study
  • Autologous bone marrow transplant or stem cell rescue within 4 months prior to study treatment
  • Use of biologic response modifiers, such as G-CSF, within 3 week of study entry. [G-CSF and other hematopoietic growth factors may be used in the management of acute toxicity such as febrile neutropenia when clinically indicated or at the discretion of the investigator, however, they may not be substituted for a required dose reduction.] [Patients taking chronic erythropoietin are permitted provided no dose adjustment is undertaken within 2 months prior to the study or during the study]
  • Investigational drug therapy outside of this trial during or within 4 weeks of study entry
  • Prior exposure to the study drug.
  • Any St. John´s wort containing remedy
  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 ClinicalTrials.gov identifier: NCT00889343

  Show 57 Study Locations
Sponsors and Collaborators
AIO-Studien-gGmbH
Investigators
Principal Investigator: Thomas Höhler, Prof. Dr. med.
  More Information

Additional Information:
No publications provided

Responsible Party: AIO-Studien-gGmbH
ClinicalTrials.gov Identifier: NCT00889343     History of Changes
Other Study ID Numbers: AIO KRK 0307
Study First Received: April 17, 2009
Last Updated: March 1, 2013
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by AIO-Studien-gGmbH:
Second-line therapy of metastatic colorectal cancer
Sorafenib
Colorectal Neoplasms
palliative therapy
after progression of firstline therapy with an Oxaliplatin- or Irinotecan based Fluoropyrimidine containing regimen ± bevacizumab

Additional relevant MeSH terms:
Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Fluorouracil
Oxaliplatin
Irinotecan
Sorafenib
Leucovorin
Levoleucovorin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on July 26, 2014