AT7519M in Treating Patients With Advanced or Metastatic Solid Tumors or Refractory Non-Hodgkin's Lymphoma
RATIONALE: AT7519M may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
PURPOSE: This phase I trial is studying the side effects and best dose of AT7519M in treating patients with advanced or metastatic solid tumors or refractory non-Hodgkin's lymphoma.
|Lymphoma Unspecified Adult Solid Tumor, Protocol Specific||Drug: CDKI AT7519 Other: laboratory biomarker analysis||Phase 1|
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Study of AT7519M Given Twice Weekly in Patients With Advanced Incurable Malignancy|
- Maximum tolerated dose as assessed by NCI CTCAE v.30 [ Time Frame: from time of 1st dose ]
- Safety, tolerability, toxicity profile, and dose-limiting toxicities as assessed by NCI CTCAE v.30 [ Time Frame: from time of 1st dose ]
- Pharmacokinetic profile as measured on days 1, 2, and 4 in course 1 [ Time Frame: one month ]during cycle 1
- Correlation of toxicity profile with pharmacokinetics [ Time Frame: after completion of each dose level ]
- Preliminary antitumor activity of treatment in patients with measurable disease [ Time Frame: Every 60 days ]after every second cycle
- Overall response (complete and partial response) rate [ Time Frame: Every 60 days ]after every second cycle
- Response duration (median and range) [ Time Frame: after progression ]
|Study Start Date:||August 2006|
|Study Completion Date:||January 2013|
|Primary Completion Date:||March 2012 (Final data collection date for primary outcome measure)|
Experimental: CDKI AT7519
AT7519M (1 hour IV) on days 1, 4, 8 and 11 every 5 weeks.
Drug: CDKI AT7519
AT7519M (1 hour IV) on days 1, 4, 8 and 11 every 5 weeks.Other: laboratory biomarker analysis
Pharmacokinetic bioanalysis of the AT7519 plasma concentration data will be performed by BioDynamics Northhampton, U.K. The pharmacokinetic parameters for AT7519 will be determined by Astex Therapeutics as data permits.
- Determine the recommended phase II dose of AT7519M in patients with advanced or metastatic solid tumors or refractory non-Hodgkin's lymphoma.
- Determine the safety, tolerability, toxicity profile, and dose-limiting toxicities of this drug in these patients.
- Determine the pharmacokinetic profile of this drug in these patients.
- Correlate the toxicity profile with pharmacokinetics of this drug in these patients.
- Assess, preliminarily, the antitumor activity of this drug in these patients.
OUTLINE: This is an open-label, dose-escalation, multicenter study.
Patients receive AT7519M IV over 1-3 hours on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of AT7519M until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity during course 1. Once the MTD has been determined, up to 8 additional patients are treated at the MTD.
Patients undergo blood collection periodically for pharmacokinetic studies. Patients treated at the MTD also undergo tumor tissue biopsies or aspirates and blood collection periodically for additional pharmacodynamic and correlative biomarker studies.
After completion of study therapy, patients are followed at 4 weeks. Patients with complete response, partial response, or stable disease are followed every 3 months thereafter until relapse.
PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00390117
|Juravinski Cancer Centre at Hamilton Health Sciences|
|Hamilton, Ontario, Canada, L8V 5C2|
|Univ. Health Network-Princess Margaret Hospital|
|Toronto, Ontario, Canada, M5G 2M9|
|Study Chair:||Sebastien Hotte, MD||Margaret and Charles Juravinski Cancer Centre|
|Study Chair:||Eric X. Chen, MD, PhD||Princess Margaret Hospital, Canada|