AT7519M in Treating Patients With Advanced or Metastatic Solid Tumors or Refractory Non-Hodgkin's Lymphoma

Sponsor

NCIC Clinical Trials Group (Other)

Overall Status

Completed

CT.gov ID

NCT00390117

Collaborator

(none)

Enrollment

Locations

Arm

76.6

Actual Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma Unspecified Adult Solid Tumor, Protocol Specific	Drug: CDKI AT7519 Other: laboratory biomarker analysis	Phase 1

Detailed Description

OBJECTIVES:

Primary

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.

Secondary

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

34 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I Study of AT7519M Given Twice Weekly in Patients With Advanced Incurable Malignancy

Actual Study Start Date :

Aug 22, 2006

Actual Primary Completion Date :

Mar 13, 2012

Actual Study Completion Date :

Jan 10, 2013

Arms and Interventions

Arm	Intervention/Treatment
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.

Arm

Intervention/Treatment

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.

Outcome Measures

Primary Outcome Measures

Maximum tolerated dose as assessed by NCI CTCAE v.30 [from time of 1st dose]
Safety, tolerability, toxicity profile, and dose-limiting toxicities as assessed by NCI CTCAE v.30 [from time of 1st dose]
Pharmacokinetic profile as measured on days 1, 2, and 4 in course 1 [one month]
during cycle 1
Correlation of toxicity profile with pharmacokinetics [after completion of each dose level]

Secondary Outcome Measures

Preliminary antitumor activity of treatment in patients with measurable disease [Every 60 days]
after every second cycle
Overall response (complete and partial response) rate [Every 60 days]
after every second cycle
Response duration (median and range) [after progression]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically or cytologically confirmed diagnosis of 1 of the following:
Advanced and/or metastatic solid tumor
No more than 3 prior regimens for metastatic disease
Refractory non-Hodgkin's lymphoma
Clinically or radiologically documented disease
Patients whose only evidence of disease is tumor marker elevation are not eligible
No untreated brain or meningeal metastases
Patients with radiologic or clinical evidence of stable, treated brain metastases are eligible provided they are asymptomatic AND have no requirement for corticosteroids

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
Absolute granulocyte count ≥ 1,500/mm³
Platelet count ≥ 100,000/mm³
Creatinine ≤ 1.25 times upper limit of normal (ULN) OR creatinine clearance ≥ 50 mL/min
Bilirubin normal
ALT and AST ≤ 2 times ULN (5 times ULN if patient has documented liver metastases)
Potassium normal
Calcium normal
Creatine kinase (CK or CPK) ≤ 2 times ULN
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No pre-existing cardiovascular conditions and/or symptomatic cardiac dysfunction, including any of the following:
Significant cardiac event (including symptomatic heart failure or angina) within the past 3 months or any cardiac disease that, in the opinion of the investigator, increases the risk for ventricular arrhythmia
Any history of ventricular arrhythmia, which was symptomatic or required treatment (CTC grade 3), including multifocal PVCs, bigeminy, trigeminy, or ventricular tachycardia
Uncontrolled hypertension
Previous history of QT prolongation with other medication
Congenital long QT syndrome
QT and QTc, with Bazett's correction, unmeasurable or ≥ 460 msec on screening ECG
LVEF < 45 % by MUGA for patients with significant cardiac history (i.e., myocardial infarction, severe hypertension, or arrhythmia) or prior doxorubicin (> 450 mg/m²)
No active or uncontrolled infections
No serious illness or medical condition that would preclude study compliance
No peripheral neuropathy > grade 1

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
At least 21 days since prior cytotoxic chemotherapy and recovered (solid tumors)
At least 21 days since prior palliative radiotherapy and recovered
Exceptions may be made for low-dose, nonmyelosuppressive radiotherapy
Prior hormonal, immunologic, biologic, or signal transduction inhibitor therapy allowed
At least 14 days since prior major surgery and recovered (no nonhealing wounds)
At least 4 weeks since prior steroids
No other concurrent medications which affect QT/QTc and cannot be discontinued
No other concurrent experimental drugs or anticancer therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Juravinski Cancer Centre at Hamilton Health Sciences	Hamilton	Ontario	Canada	L8V 5C2
2	Univ. Health Network-Princess Margaret Hospital	Toronto	Ontario	Canada	M5G 2M9