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A Phase I Study of AFP464 (Aminoflavone Prodrug) in Patients With Advanced Solid Tumors

Phase 1
18 Years
Not Enrolling
Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

A Phase I Study of AFP464 (Aminoflavone Prodrug) in Patients With Advanced Solid Tumors


I. Determine the dose-limiting toxicity and maximum tolerated dose of AFP464 in patients
with advanced solid tumors.

II. Assess the safety and tolerability of this drug in these patients.


I. Observe clinical response in patients treated with this drug. II. Characterize the
pharmacokinetics of this drug in these patients. III. 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.

Inclusion Criteria:

- Bilirubin normal

- Platelet count >= 100,000/mm³

- 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

- 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

- 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

- 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

- Tumor amenable to biopsy (maximum tolerated dose expansion cohort)

- No known brain metastases

- ECOG performance status (PS) 0-2 OR Karnofsky PS 60-100%

- Life expectancy > 12 weeks

- Absolute neutrophil count >= 1,500/mm³

- No other concurrent anticancer agents or therapies

- Renal cell cancer, breast cancer, and non-small cell lung cancer encouraged

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose determined by dose-limiting toxicity

Outcome Time Frame:

28 days

Safety Issue:


Principal Investigator

Patricia LoRusso

Investigator Role:

Principal Investigator

Investigator Affiliation:

Wayne State University


United States: Food and Drug Administration

Study ID:




Start Date:

June 2006

Completion Date:

Related Keywords:

  • Unspecified Adult Solid Tumor, Protocol Specific
  • Neoplasms



Wayne State University Detroit, Michigan  48202