3-AP and Doxorubicin In Treating Patients With Metastatic or Refractory Solid Tumors - Full Text View

Sponsor:	University of Wisconsin, Madison
Collaborator:	National Cancer Institute (NCI)
Information provided by:	University of Wisconsin, Madison
ClinicalTrials.gov Identifier:	NCT00079014

Purpose

RATIONALE: Drugs used in chemotherapy, such as doxorubicin, work in different ways to stop tumor cells from dividing so they stop growing or die. 3-AP may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth and may help doxorubicin kill more cancer cells by making them more sensitive to the drug.

PURPOSE: This phase I trial is studying the side effects and best dose of 3-AP and doxorubicin in treating patients with metastatic or refractory solid tumors.

Condition	Intervention	Phase
Unspecified Adult Solid Tumor, Protocol Specific	Drug: doxorubicin hydrochloride Drug: triapine	Phase I

Study Type:	Interventional
Study Design:	Primary Purpose: Treatment
Official Title:	A Phase I Triapine In Combination With Doxorubicin In Refractory Tumors

Resource links provided by NLM:

MedlinePlus related topics: Cancer

Drug Information available for: Doxorubicin Doxorubicin hydrochloride 3-Aminopyridine-2-carboxaldehyde thiosemicarbazone

U.S. FDA Resources

Further study details as provided by University of Wisconsin, Madison:

Primary Outcome Measures:

Maximum tolerated dose at first course [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Toxicity at first and second course [ Designated as safety issue: Yes ]
Antitumor activity at first and second course [ Designated as safety issue: No ]

Estimated Enrollment:	36
Study Start Date:	March 2004
Primary Completion Date:	July 2008 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

Determine the maximum tolerated dose of 3-AP (Triapine^®) when administered with doxorubicin in patients with metastatic or refractory solid tumors.

Secondary

Determine the toxicity profile of this regimen in these patients.
Determine any antitumor activity of this regimen in these patients.
Determine the pharmacokinetic profile of this regimen in these patients.

OUTLINE: This is a dose-escalation study of 3-AP (Triapine^®).

Patients receive doxorubicin IV over 15 minutes on day 1 and 3-AP (Triapine®) IV over 2 hours on days 1-4. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of 3-AP (Triapine®) 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. Once the MTD is determined, an additional 6 patients are treated at that dose level.

Patients are followed until disease progression.

PROJECTED ACCRUAL: A total of 3-36 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 confirmed solid tumor
- Metastatic or unresectable disease
Measurable or evaluable disease
Not amenable to available standard curative or palliative chemotherapy
No known brain metastasis

PATIENT CHARACTERISTICS:

Age

18 and over

Performance status

ECOG 0-2

Life expectancy

More than 12 weeks

Hematopoietic

Absolute neutrophil count ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
WBC ≥ 3,000/mm^3
No G6PD deficiency (i.e., ≥ lower limit of normal)

Hepatic

AST/ALT ≤ 2.5 times upper limit of normal
Bilirubin normal

Renal

Creatinine ≤ 1.5 mg/dL OR
Creatinine clearance ≥ 60 mL/min

Cardiovascular

LVEF > 45%
No symptomatic congestive heart failure
No unstable angina pectoris
No cardiac arrhythmia

Pulmonary

Oxygen saturation 95-100%
No severe pulmonary disease requiring oxygen therapy

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 30 days after study treatment
No prior allergic reaction to compounds of similar chemical or biological composition to 3-AP (Triapine®) or any other study agent
No other concurrent uncontrolled illness
No active or ongoing infection
No psychiatric illness or social situation that would preclude study compliance
No toxicity > grade 1 from prior therapy

PRIOR CONCURRENT THERAPY:

Biologic therapy

No concurrent filgrastim (G-CSF) or sargramostim (GM-CSF) during course 1 of study treatment
- Concurrent G-CSF and GM-CSF allowed during subsequent courses at the discretion of the principal investigator

Chemotherapy

More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
No prior anthracyclines

Endocrine therapy

Not specified

Radiotherapy

More than 4 weeks since prior radiotherapy and recovered
No prior radiotherapy to more than 25% of bone marrow

Surgery

Not specified

Other

No other concurrent investigational agents
No concurrent combination antiretroviral therapy for HIV-positive patients

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00079014

Locations

United States, Wisconsin
University of Wisconsin Comprehensive Cancer Center
Madison, Wisconsin, United States, 53792-6164

Sponsors and Collaborators

University of Wisconsin, Madison

National Cancer Institute (NCI)

Investigators

Study Chair:

George Wilding, MD

University of Wisconsin, Madison

More Information

Additional Information:

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

Publications:

Schelman WR, Morgan-Meadows S, Marnocha R, Lee F, Eickhoff J, Huang W, Pomplun M, Jiang Z, Alberti D, Kolesar JM, Ivy P, Wilding G, Traynor AM. A phase I study of Triapine in combination with doxorubicin in patients with advanced solid tumors. Cancer Chemother Pharmacol. 2009 May;63(6):1147-56. Epub 2008 Dec 13.

ClinicalTrials.gov Identifier:	NCT00079014 History of Changes
Other Study ID Numbers:	CDR0000353294, P30CA014520, WCCC-CO-03904, NCI-6266
Study First Received:	March 8, 2004
Last Updated:	March 23, 2010
Health Authority:	United States: Federal Government

Keywords provided by University of Wisconsin, Madison:

unspecified adult solid tumor, protocol specific

Additional relevant MeSH terms:

Neoplasms
Doxorubicin
Antibiotics, Antineoplastic

Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 09, 2012