Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

AFP464 in Treating Patients With Advanced Solid Tumors

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Biomarker/Laboratory analysis, Treatment	Active	18 and over	NCI	MAYO-MC0513 7380, NCI-7380, MAYO-IAB-05-00404800, MAYO-IAB-05-00404801, NCT00348699

Objectives

1. Determine the maximum tolerated dose (MTD) of AFP464 in patients with advanced solid tumors.
2. Evaluate the toxicity profile of AFP464.
3. Characterize the plasma pharmacokinetics and urinary excretion of AFP464 and aminoflavone in these patients.
4. Identify any activity of AFP464 in patients with metastatic cancer.
5. Explore whether AFP464 induces CYP1A1 expression in tumor as measured by pre- and post-treatment tumor biopsies at the MTD as well as in peripheral lymphocytes during the dose-escalation phase and at the MTD.
6. Explore the relationship between the pharmacogenetic analysis and toxicity or response.

Entry Criteria

Disease Characteristics:

• Histologically confirmed solid tumor
  • Metastatic disease refractory to available therapy OR for which no standard therapy exists



• Diagnosis of breast, ovarian, or renal cell cancer (for patients treated at the maximum tolerated dose)
  • Tumor amenable for paired tumor biopsies



• No CNS metastases



• Hormone receptor status not specified

Prior/Concurrent Therapy:

• Recovered from prior chemotherapy
• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered
• More than 4 weeks since prior immunotherapy or biologic therapy
• More than 4 weeks since prior radiotherapy
• No prior thoracic radiotherapy
• No prior radiotherapy to > 25% of the bone marrow
• No concurrent prophylactic colony-stimulating factors
• No concurrent combination antiretroviral therapy for HIV-positive patients
• No concurrent participation in another study involving a pharmacologic agent (e.g., drugs, biologics, immunotherapy, or gene therapy) for symptom control or therapeutic intent
• No other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational

Patient Characteristics:

• Male or female
• ECOG performance status 0-2
• Life expectancy ≥ 12 weeks
• Menopausal status not specified
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Hemoglobin > 9.0 g/dL
• Bilirubin normal
• AST and ALT ≤ 2.5 times upper limit of normal (ULN)
• Creatinine ≤ 1.25 times ULN OR creatinine clearance ≥ 60 mL/min
• Adequate pulmonary function, DLCO normal or asymptomatic grade 1 DLCO
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No uncontrolled 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 preclude study compliance
• No seizure disorder
• No history of allergic reactions attributed to compounds of similar chemical or biologic composition to AFP464
• No symptomatic pulmonary disease
• No active smokers or those who have smoked within the past 30 days
• Willing and able to refrain completely from smoking during study treatment
• Willing to provide biologic specimens (blood and urine)

Expected Enrollment

A total of 70 patients will be accrued for this study.

Outcomes

Overall toxicity incidence and toxicity profiles as measured by dose level and tumor site via the NCI CTCAE v 3.0
Overall response as measured by RECIST criteria every 6 weeks
Time to progression
Time to treatment failure
Pharmacokinetics and urinary excretion, computed and correlated with toxicity and response via Spearman correlation coefficients

Outline

This is a dose-escalation study followed by an open-label study.

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

Cohorts of 1-6 patients receive escalating doses of AFP464 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. An additional 10 patients with accessible metastatic breast, renal, or ovarian cancer receive AFP464 as above at the MTD.

Blood, buccal cells, and urine are collected before beginning treatment and during course 1 and examined for biomarkers and biopharmacogenetics. Patients who are treated at the MTD also undergo biopsies before and after treatment. Samples are anlayzed via real time polymerase chain reaction (RT-PCR) and immunofluorescence.

After completion of study treatment, patients are followed periodically for 3 months.

Trial Contact Information

Trial Lead Organizations

Mayo Clinic Cancer Center

Matthew Goetz, MD, Protocol chair		Ph: 507-284-4857 Email: goetz.matthew@mayo.edu

U.S.A.
Minnesota
	Rochester
	Mayo Clinic Cancer Center
		Clinical Trials Office - All Mayo Clinic Locations	Ph:  507-538-7623

Registry Information
Official Title		A Phase I Study and Pharmacological Trial of Once Weekly Aminoflavone Prodrug (AFP464) Administered 3 Out of Every 4 Weeks in Solid Tumor Patients
Trial Start Date		2006-07-18
Trial Completion Date		2007-05-14 (estimated)
Registered in ClinicalTrials.gov		NCT00348699
Date Submitted to PDQ		2006-03-07
Information Last Verified		2008-12-28
NCI Grant/Contract Number		CA69912, CA15083