AFP464 in Treating Patients With Advanced Solid Tumors - Full Text View

Sponsor:	Barbara Ann Karmanos Cancer Institute
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00369200

Purpose

RATIONALE: Drugs used in chemotherapy, such as AFP464, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing.

PURPOSE: This phase I trial is studying the side effects and best dose of AFP464 in treating patients with advanced solid tumors.

Condition	Intervention	Phase
Unspecified Adult Solid Tumor, Protocol Specific	Drug: AFP464 Other: pharmacological study	Phase I

Study Type:	Interventional
Study Design:	Treatment
Official Title:	A Phase I Study of AFP464 (Aminoflavone Prodrug) in Patients With Advanced Solid Tumors

Resource links provided by NLM:

MedlinePlus related topics: Cancer

U.S. FDA Resources

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

Primary Outcome Measures:

Dose-limiting toxicity [ Designated as safety issue: Yes ]
Maximum tolerated dose [ Designated as safety issue: Yes ]
Types and grades of toxicity [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Response rate [ Designated as safety issue: No ]
Pharmacokinetic, pharmacodynamic, and pharmacogenomic parameters [ Designated as safety issue: No ]

Estimated Enrollment:	60
Study Start Date:	June 2006
Estimated Primary Completion Date:	April 2008 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

Determine the dose-limiting toxicity and maximum tolerated dose of AFP464 in patients with advanced solid tumors.
Assess the safety and tolerability of this drug in these patients.

Secondary

Observe clinical response in patients treated with this drug.
Characterize the pharmacokinetics of this drug in these patients.
Determine the clinical significance of genetic polymorphisms on the genes coding metabolizing enzymes (e.g., CYP1A1, 1A2, 2C9, 2C19, and SULTA1) and on the disposition and efficacy/toxicity of AFP464 and AF.

OUTLINE: This a dose-escalation, multicenter study.

Patients receive AFP464 IV over 3 hours on days 1, 8, and 15. Courses repeat every 28 days in the absence of unacceptable toxicity or disease progression.

Cohorts of 2-6 patients receive escalating doses of AFP464 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which ≤ 1 of 6 patients experience dose-limiting toxicity. An additional 10 patients whose tumor is amenable to biopsy are treated at the MTD.

Patients undergo blood collection periodically for pharmacokinetic and pharmacodynamic studies. Patients treated at the MTD also undergo tumor tissue biopsies periodically for additional pharmacodynamic and correlative biomarker studies.

After completion of study treatment, patients are followed for 4 weeks.

PROJECTED ACCRUAL: A total of 60 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 malignant solid tumor that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
- Renal cell cancer, breast cancer, and non-small cell lung cancer encouraged
Tumor amenable to biopsy (maximum tolerated dose expansion cohort)
No known brain metastases

PATIENT CHARACTERISTICS:

ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%
Life expectancy > 12 weeks
Absolute neutrophil count ≥ 1,500/mm³
Platelet count ≥ 100,000/mm³
Bilirubin normal
AST and ALT ≤ 2.5 times upper limit of normal
Creatinine normal OR creatinine clearance ≥ 60 mL/min
Adequate pulmonary function
DLCO ≤ grade 1
No symptomatic pulmonary disease
Not pregnant or nursing
Fertile patients must use effective contraception
Negative pregnancy test
No history of allergic reactions attributed to compounds of similar chemical or biological composition to AFP464
No uncontrolled intercurrent illness including, but not limited to, any of the following:
- Ongoing or active infection
- Symptomatic congestive heart failure
- Unstable angina pectoris
- Cardiac arrhythmia
- Psychiatric illness or social situation that would limit study compliance
No smoking within the past 30 days
- Must be willing and able to completely refrain from smoking during study participation

PRIOR CONCURRENT THERAPY:

More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas, mitomycin C, or bleomycin) and recovered
At least 4 weeks since prior radiotherapy
- No prior thoracic radiotherapy
- No prior radiotherapy to ≥ 50% of total marrow volume
More than 4 weeks since prior experimental therapy (non-FDA-approved agents), immunotherapy, or targeted agents and recovered
More than 8 weeks since prior UCN-01
More than 2 weeks since prior hormonal therapy except for patients on androgen suppression for prostate cancer
- Concurrent androgen suppression allowed in patients with prostate cancer
No concurrent combination antiretroviral therapy for HIV-positive patients
No other concurrent investigational agents
No other concurrent anticancer agents or therapies

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00369200

Locations

United States, Michigan
Barbara Ann Karmanos Cancer Institute	Recruiting
Detroit, Michigan, United States, 48201-1379
Contact: Clinical Trials Office - Barbara Ann Karmanos Cancer Institute 313-576-9363
Sinai-Grace Hospital	Recruiting
Detroit, Michigan, United States, 48235
Contact: Elisabeth Heath 313-576-8717

Sponsors and Collaborators

Barbara Ann Karmanos Cancer Institute

National Cancer Institute (NCI)

Investigators

Study Chair:

Elisabeth I. Heath, MD

Barbara Ann Karmanos Cancer Institute

More Information

Additional Information:

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

No publications provided

Study ID Numbers:	CDR0000492006, WSU-2006-011, NCI-7378
Study First Received:	August 24, 2006
Last Updated:	August 11, 2009
ClinicalTrials.gov Identifier:	NCT00369200 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

unspecified adult solid tumor, protocol specific

Additional relevant MeSH terms:

Neoplasms

ClinicalTrials.gov processed this record on February 08, 2010