A Phase I Trial Evaluating mFOLFOX6 and Avastin With Nexavar as First-Line Treatment for Metastatic Colorectal Cancer

This study has been terminated.

( Dose limiting toxicity at the lowest planned dose level. )

Study NCT00779311 Information provided by Accelerated Community Oncology Research Network

First Received on October 23, 2008. Last Updated on October 31, 2011 History of Changes

Results First Received: September 9, 2011

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study; Intervention Model: Single Group Assignment; Masking: Open Label; Primary Purpose: Treatment
Condition:	Metastatic Colorectal Cancer
Interventions:	Drug: sorafenib Drug: bevacizumab Drug: mFOLFOX6 regimen

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Three community oncology research sites across the US within the ACORN Network participated in this study. Enrollment started in October 2008 and was closed early in April 2010 due to two subjects experiencing DLT at the lowest dose level.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Informed consent was obtained from all subjects. All subjects underwent a screening period that could last up to 4 weeks during which pre-study assessments were completed. All subjects received mFOLFOX6, bevacizumab, and sorafenib. Subjects were assigned to a Dosage Level at the time of enrollment.

Reporting Groups

	Description
Dose Level (DL) 1 for MTD Determination	All eligible patients will receive the mFOLFOX6 regimen at full dose followed by IV bevacizumab 5mg/kg on Day 1 of each treatment cycle, and sorafenib 200mg every other day.
Dose Level (DL) 2 for MTD Determination	All eligible patients will receive the mFOLFOX6 regimen at full dose followed by IV bevacizumab 5mg/kg on Day 1 of each treatment cycle, and sorafenib 200mg every day.
Dose Level (DL) 3 for MTD Determination	All eligible patients will receive the mFOLFOX6 regimen at full dose followed by IV bevacizumab 5mg/kg on Day 1 of each treatment cycle, and sorafenib 200mg twice a day, 5 days on followed by 2 days off.
Dose Level (DL) 4 for MTD Determination	All eligible patients will receive the mFOLFOX6 regimen at full dose followed by IV bevacizumab 5mg/kg on Day 1 of each treatment cycle, and sorafenib 200mg twice a day.
Dose Level (DL) 5 for MTD Determination	All eligible patients will receive the mFOLFOX6 regimen at full dose followed by IV bevacizumab 5mg/kg on Day 1 of each treatment cycle, and sorafenib 400mg twice a day.

Participant Flow: Overall Study

	Dose Level (DL) 1 for MTD Determination	Dose Level (DL) 2 for MTD Determination	Dose Level (DL) 3 for MTD Determination	Dose Level (DL) 4 for MTD Determination	Dose Level (DL) 5 for MTD Determination
STARTED	8 ^[1]	0	0	0	0
Dose Limiting Toxicity (DLT) Evaluation	6	0	0	0	0
COMPLETED	8	0	0	0	0
NOT COMPLETED	0	0	0	0	0

[1]	2 of 6 patients were not evaluable for DLT assessment and were replaced for a total of 8 enrolled.

Baseline Characteristics

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Reporting Groups

	Description
Dose Level (DL) 1 for MTD Determination	All eligible patients will receive the mFOLFOX6 regimen at full dose followed by IV bevacizumab 5mg/kg on Day 1 of each treatment cycle, and sorafenib 200mg every other day.
Dose Level (DL) 2 for MTD Determination	All eligible patients will receive the mFOLFOX6 regimen at full dose followed by IV bevacizumab 5mg/kg on Day 1 of each treatment cycle, and sorafenib 200mg every day.
Dose Level (DL) 3 for MTD Determination	All eligible patients will receive the mFOLFOX6 regimen at full dose followed by IV bevacizumab 5mg/kg on Day 1 of each treatment cycle, and sorafenib 200mg twice a day, 5 days on followed by 2 days off.
Dose Level (DL) 4 for MTD Determination	All eligible patients will receive the mFOLFOX6 regimen at full dose followed by IV bevacizumab 5mg/kg on Day 1 of each treatment cycle, and sorafenib 200mg twice a day.
Dose Level (DL) 5 for MTD Determination	All eligible patients will receive the mFOLFOX6 regimen at full dose followed by IV bevacizumab 5mg/kg on Day 1 of each treatment cycle, and sorafenib 400mg twice a day.

Baseline Measures

	Dose Level (DL) 1 for MTD Determination	Dose Level (DL) 2 for MTD Determination	Dose Level (DL) 3 for MTD Determination	Dose Level (DL) 4 for MTD Determination	Dose Level (DL) 5 for MTD Determination	Total
Number of Participants [units: participants]	8	0	0	0	0	8
Age [units: participants]
<=18 years	0					0
Between 18 and 65 years	3					3
>=65 years	5					5
Age [units: years] Mean ± Standard Deviation	62.0 ± 11.40					62.0 ± 11.40
Gender [units: participants]
Female	3					3
Male	5					5
Region of Enrollment [units: participants]
United States	8					8

Outcome Measures

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1. Primary:

Determination of the Maximum Tolerated Dose (MTD) of Sorafenib When Given in Combination With mFOLFOX6 and Bevacizumab [ Time Frame: MTD was assessed during the first 2 cycles of treatment (i.e., the first 4 weeks of treatment since cycle length is 2 weeks) ]

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2. Secondary:

Determination of Progression Free Survival (PFS) Among Patients on This Regimen [ Time Frame: PFS was measured from day 1 of treatment until time of progression (assessed every 8 weeks) or death, whichever came first. ]

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3. Secondary:

Determination of Quality of Life (QoL) as Indicated by Patient Care Monitor (PCM) Data Among Patients on This Regimen [ Time Frame: The PCM questionnaire was administered on day 1 of each cycle (approximately every 2 weeks) during study treatment. ]

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Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: Prior to publication or presentation of Sponsored Research results, Researcher agrees to provide Bayer with such presentation, abstract, or manuscript at least 30 days prior to its presentation or submission for the sole purpose of allowing Bayer to redact Confidential Information and protect any existing or future patents.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Early termination due to the MTD determined to be Dose Level 1, leading to a small number of subjects analyzed.

Results Point of Contact:

Name/Title: Vice President of Scientific Affairs
Organization: Accelerated Community Oncology Research Network, Inc.
phone: 901-435-5570
e-mail: mwalker@acorncro.com

No publications provided

Responsible Party:	Accelerated Community Oncology Research Network
ClinicalTrials.gov Identifier:	NCT00779311 History of Changes
Other Study ID Numbers:	AFMSMCRC0706
Study First Received:	October 23, 2008
Results First Received:	September 9, 2011
Last Updated:	October 31, 2011
Health Authority:	United States: Institutional Review Board