Clinical trial NCT00934882: Study to Determine Safety, Pharmacokinetics, Pharmacodynamics of BAY73-4506 in Combination With mFOLFOX6 or FOLFIRI
Official title: Phase I, Open-label, Non-placebo Controlled Study to Determine the Safety, Pharmacokinetics, and Pharmacodynamics of BAY73-4506 in Combination With mFOLFOX6 or FOLFIRI as First or Second Line Therapy in Patients With Metastatic Colorectal.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Colorectal Neoplasms
Keywords: Colorectal cancer
Targeted therapy
Multi-kinase inhibitor
FOLFOX
FOLFIRI
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2009-07-08
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This multi-center, open-label, non-randomized, non-placebo-controlled, Phase I study will define the safety profile and tumor response profile of the multi-kinase inhibitor BAY73-4506 as oral treatment in combination with the chemotherapy regimen mFOLFOX6 or FOLFIRI in patients with metastatic CRC. It will also determine the impact of the combined administration on the concentration of drugs over time (pharmacokinetics) of BAY73-4506, oxaliplatin, 5 FU, and irinotecan.

This study will be conducted at approximately 5 - 8 study centers in Germany. Up to 60 patients will be enrolled into this study to ensute that at least 12 - 15 patients for each combination regimen can be evaluated for safety and pharmacokinetics. For this reason a minimum of 20 patients will receive mFOLFOX6 in combination with BAY73-4506 and at least 20 patients will receive FOLFIRI in combination with BAY73-4506.


Eligibility criteria: Inclusion Criteria:

* Histological or cytological documentation of adenocarcinoma of the colon or rectum.
* At least 1 measurable lesion as per RECIST
* ECOG Performance Status of 0 - 1
* Life expectancy of at least 12 weeks.
* Adequate bone marrow, liver, and renal function

Exclusion Criteria:

* More than 1 previous chemotherapy for Colorectal Cancer. Adjuvant chemotherapy for Colorectal Cancer (Stage I, II, II) is permitted, if the adjuvant therapy ended \>6 month before screening.
* Previous FOLFOX treatment for patients who will be included in the mFOLFOX6 cohort apart from FOLFOX treatment in an adjuvant setting.
* Previous FOLFIRI treatment for patients who will be included in the FOLFIRI cohort.

Primary outcomes:
measure: Adverse Event Collection
timeFrame: 3 years
measure: Effect of BAY73-4506 on the pharmacokinetics of mFOLFOX6 and FOLFIRI (Cmax, AUC, through concentration of BAY73-4506 and Cmax, AUC of Platinum, Irinotecan and its metabolite SN-38, 5-Flourouracil)
timeFrame: Cycle 1 and Cycle 2
Secondary outcomes:
measure: Biomarker status
timeFrame: Screening, Cycle 1, Cycle 2, Cycle 3
measure: Pharmacodynamic parameters
timeFrame: 3 years
measure: Tumor response
timeFrame: 3 years
Other outcomes:
Locations:
city: Freiburg
country: Germany
state: Baden-Württemberg
city: Heidelberg
country: Germany
state: Baden-Württemberg
city: Mannheim
country: Germany
state: Baden-Württemberg
city: Oldenburg
country: Germany
state: Niedersachsen
city: Herne
country: Germany
state: Nordrhein-Westfalen
city: Köln
country: Germany
state: Nordrhein-Westfalen
city: Dresden
country: Germany
state: Sachsen
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: Schultheis B, Folprecht G, Kuhlmann J, Ehrenberg R, Hacker UT, Kohne CH, Kornacker M, Boix O, Lettieri J, Krauss J, Fischer R, Hamann S, Strumberg D, Mross KB. Regorafenib in combination with FOLFOX or FOLFIRI as first- or second-line treatment of colorectal cancer: results of a multicenter, phase Ib study. Ann Oncol. 2013 Jun;24(6):1560-7. doi: 10.1093/annonc/mdt056. Epub 2013 Mar 13.