Phase I, Dosage-finding and PK Study of IV Topotecan and Erlotinib With Refractory Solid Tumors

This study has been completed.

Sponsor:

Collaborators:

GlaxoSmithKline

Genentech

Information provided by (Responsible Party):

Accelerated Community Oncology Research Network

ClinicalTrials.gov Identifier:

NCT00611468

First received: January 29, 2008

Last updated: August 18, 2011

Last verified: August 2011

History of Changes

Results First Received: July 1, 2010

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety Study; Intervention Model: Single Group Assignment; Masking: Open Label; Primary Purpose: Treatment
Condition:	Metastatic Solid Tumor
Interventions:	Drug: Topotecan Drug: Erlotinib

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
The study was open to enrollment at one community oncology clinic from June 2006 to November 2008.

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 both topotecan and erlotinib. Subjects were assigned to a Dosage Level at the time of enrollment.

Reporting Groups

	Description
Dosage Level 1 for MTD Determination	Dosage level 1 was topotecan 0.75 mg/m2 and erlotinib 150 mg.
Dosage Level 2 for MTD Determination	Dosage level 2 was topotecan 1.0 mg/m2 and erlotinib 150 mg.
Dosage Level 3 for MTD Determination	Dosage level 3 was topotecan 1.25 mg/m2 and erlotinib 150 mg.
PK Group for Additional PK Data	Additional patients were enrolled for enhanced PK parameter estimation

Participant Flow: Overall Study

	Dosage Level 1 for MTD Determination	Dosage Level 2 for MTD Determination	Dosage Level 3 for MTD Determination	PK Group for Additional PK Data
STARTED	3	7	6	13
COMPLETED	3	6 ^[1]	6	13
NOT COMPLETED	0	1	0	0

[1]	One subject did not complete Cycle 1 of treatment and was replaced.

Baseline Characteristics

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Reporting Groups

	Description
Treatment Group: Intravenous Topotecan and Oral Erlotinib	All subjects received both topotecan and erlotinib. Subjects were assigned to a Dosage Level at the time of enrollment. Dosage level 1 was topotecan 0.75mg/m2 and erlotinib 150mg. Dosage level 2 was topotecan 1.0mg/m2 and erlotinib 150mg. Dosage level 3 was topotecan 1.25mg/m2 and erlotinib 150mg. Topotecan was administered intravenously on days 1 through 5 of each cycle. Erlotinib was administered orally daily. Cycle length was 21 days.

Description

Treatment Group: Intravenous Topotecan and Oral Erlotinib

All subjects received both topotecan and erlotinib. Subjects were assigned to a Dosage Level at the time of enrollment. Dosage level 1 was topotecan 0.75mg/m2 and erlotinib 150mg. Dosage level 2 was topotecan 1.0mg/m2 and erlotinib 150mg. Dosage level 3 was topotecan 1.25mg/m2 and erlotinib 150mg. Topotecan was administered intravenously on days 1 through 5 of each cycle. Erlotinib was administered orally daily. Cycle length was 21 days.

Baseline Measures

	Treatment Group: Intravenous Topotecan and Oral Erlotinib
Number of Participants [units: participants]	29
Age [units: participants]
<=18 years	0
Between 18 and 65 years	21
>=65 years	8
Age [units: years] Mean ± Standard Deviation	58.5 ± 10.3
Gender [units: participants]
Female	19
Male	10
Race (NIH/OMB) [units: participants]
American Indian or Alaska Native	0
Asian	0
Native Hawaiian or Other Pacific Islander	0
Black or African American	8
White	21
More than one race	0
Unknown or Not Reported	0
Region of Enrollment [units: participants]
United States	29

Outcome Measures

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1. Primary:

Maximum Tolerated Dosage (MTD) of Intravenous Topotecan When Given in Combination With Oral Erlotinib [ Time Frame: MTD was assessed during the first cycle of combination topotecan and erlotinib therapy (days 1-21). ]

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2. Primary:

Dosage Limiting Toxicities [ Time Frame: DLT were assessed during the first cycle of combination topotecan and erlotinib therapy (days 1-21) ]

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3. Primary:

Pharmacokinetic Parameters of Intravenous Topotecan With and Without Erlotinib (Mean Clearance) [ Time Frame: Day 1 Week 1 and Day 1 Week 3 ]

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4. Primary:

Pharmacokinetic Parameters of Intravenous Topotecan With and Without Erlotinib (Renal Clearance) [ Time Frame: Day 1 Week 1 and Day 1 Week 3 ]

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5. Primary:

Pharmacokinetic Parameters of Intravenous Topotecan With and Without Erlotinib (Dose-Normalized AUC) [ Time Frame: Day 1 Week 1 and Day 1 Week 3 ]

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6. Secondary:

Pharmacogenetic Analysis (CYP3A4/5 Polymorphisms, UGT1A1, BCRP, and MDR1 Genotypes) [ Time Frame: Baseline ]

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7. Secondary:

Objective Response (as Determined Using RECIST 1.0 Criteria) [ Time Frame: Every 6 weeks until the end of 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: 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 90 days from the time submitted to the sponsor for review.

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
No text entered.

Results Point of Contact:

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

No publications provided

Responsible Party:	Accelerated Community Oncology Research Network
ClinicalTrials.gov Identifier:	NCT00611468 History of Changes
Other Study ID Numbers:	ACORN ALSSRST0501
Study First Received:	January 29, 2008
Results First Received:	July 1, 2010
Last Updated:	August 18, 2011
Health Authority:	United States: Institutional Review Board

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