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

Sponsored by:	National Cancer Institute of Canada
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00390117

Purpose

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	Intervention	Phase
Lymphoma Unspecified Adult Solid Tumor, Protocol Specific	Drug: CDKI AT7519 Procedure: biopsy Procedure: laboratory biomarker analysis Procedure: pharmacological study	Phase I

MedlinePlus related topics: Cancer Lymphoma

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	A Phase I Study of AT7519M Given Twice Weekly in Patients With Advanced Incurable Malignancy

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Maximum tolerated dose as assessed by NCI CTCAE v.30 [ Designated as safety issue: Yes ]
Safety, tolerability, toxicity profile, and dose-limiting toxicities as assessed by NCI CTCAE v.30 [ Designated as safety issue: Yes ]
Pharmacokinetic profile as measured on days 1, 2, and 4 in course 1 [ Designated as safety issue: No ]
Correlation of toxicity profile with pharmacokinetics [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Preliminary antitumor activity of treatment in patients with measurable disease [ Designated as safety issue: No ]
Overall response (complete and partial response) rate [ Designated as safety issue: No ]
Response duration (median and range) [ Designated as safety issue: No ]

Estimated Enrollment:	30
Study Start Date:	August 2006
Estimated Primary Completion Date:	August 2009 (Final data collection date for primary outcome measure)

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically or cytologically confirmed diagnosis of 1 of the following:
- Advanced and/or metastatic solid tumor
  - No more than 2 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)
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No untreated or uncontrolled hypertension, cardiovascular conditions, and/or symptomatic cardiac dysfunction
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 experimental drugs or anticancer therapy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00390117

Locations

Canada, Ontario
Margaret and Charles Juravinski Cancer Centre	Recruiting
Hamilton, Ontario, Canada, L8V 5C2
Contact: Sebastien Hotte 905-387-9495
Princess Margaret Hospital	Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: Eric (Xueyu) Chen 416-946-2263

Sponsors and Collaborators

National Cancer Institute of Canada

Investigators

Investigator:	Sebastien Hotte, MD	Margaret and Charles Juravinski Cancer Centre
Study Chair:	Eric X. Chen, MD, PhD	Princess Margaret Hospital, Canada

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Study ID Numbers:	CDR0000507621, CAN-NCIC-IND177
Study First Received:	October 18, 2006
Last Updated:	July 23, 2008
ClinicalTrials.gov Identifier:	NCT00390117
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

unspecified adult solid tumor, protocol specific
recurrent adult Burkitt lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma

recurrent mantle cell lymphoma
recurrent marginal zone lymphoma
recurrent small lymphocytic lymphoma
Waldenstrom macroglobulinemia
recurrent adult grade III lymphomatoid granulomatosis
adult nasal type extranodal NK/T-cell lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
splenic marginal zone lymphoma

Study placed in the following topic categories:

Lymphoma, Mantle-Cell
Lymphoma, Follicular
Lymphoma, small cleaved-cell, diffuse
Lymphoma, B-Cell, Marginal Zone
Lymphoma, large-cell, immunoblastic
Lymphoma, B-Cell
Lymphoma, large-cell
Lymphomatoid granulomatosis
Burkitt's lymphoma
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, T-Cell
Lymphoma, Large-Cell, Immunoblastic
Waldenstrom macroglobulinemia
Lymphoma
Chronic lymphocytic leukemia

Lymphomatoid Granulomatosis
Lymphoma, Large B-Cell, Diffuse
Immunoproliferative Disorders
Leukemia, B-cell, chronic
Lymphoblastic lymphoma
Mantle cell lymphoma
Recurrence
Lymphatic Diseases
Waldenstrom Macroglobulinemia
Burkitt Lymphoma
B-cell lymphomas
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Follicular lymphoma

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Histologic Type
Immune System Diseases

ClinicalTrials.gov processed this record on January 15, 2009