Study to Determine Safety, Pharmacokinetics, Pharmacodynamics of BAY73-4506 in Combination With mFOLFOX6 or FOLFIRI

Study Overview
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Brief Summary
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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.

Official Title
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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.

Conditions
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Colorectal Neoplasms

Intervention / Treatment
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* Drug: Regorafenib (BAY73-4506)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br> | Drug: Regorafenib (BAY73-4506)<br>* Administration of the multi-kinase inhibitor BAY73-4506 (160 mg once daily from Day 4 to Day 10 and from Day 18 to Day 24) as oral treatment in combination with the chemotherapy regimen mFOLFOX6 or FOLFIRI in patients with metastatic Colorectal Cancer<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Event Collection |  | 3 years | 
| 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) |  | Cycle 1 and Cycle 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biomarker status |  | Screening, Cycle 1, Cycle 2, Cycle 3 | 
| Pharmacodynamic parameters |  | 3 years | 
| Tumor response |  | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Colorectal cancer, Targeted therapy, Multi-kinase inhibitor, FOLFOX, FOLFIRI