AFP464 in Treating Patients With Advanced Solid Tumors

A Phase 1 Study of AFP464 (Aminoflavone Prodrug) in Patients With Advanced Solid Tumors

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

Study Overview

• Status: Terminated
• Conditions: Unspecified Adult Solid Tumor, Protocol Specific
• Intervention / Treatment: Other: laboratory biomarker analysis; Other: pharmacological study; Drug: AFP464

Detailed Description

PRIMARY OBJECTIVES:

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.

SECONDARY OBJECTIVES:

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.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Wayne State University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 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
• 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 effective
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Arm I; 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.

Other: laboratory biomarker analysis; Correlative study; Other: pharmacological study; Correlative study; Other Names: pharmacological studies; Drug: AFP464; Given IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum tolerated dose determined by dose-limiting toxicity		28 days
Types and grades of toxicity	Full frequency distributions of grade of toxicity, by toxicity type, will be generated, by dose level. Among all treated patients, both point and exact confidence interval estimates of the rate of every specific type of Grade 3-4 toxicity will be calculated, by dose level. Grade 2 DLCO rates (point and confidence level) will also be computed, by dose level.	Up to 4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic, pharmacodynamic, and pharmacogenomic parameters		Up to 4 weeks
Response rate	Point and exact confidence interval estimates of response rate will be provided for all eligible patients combined, and if warranted, by specific dose levels.	Up to 4 weeks

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: June 1, 2006
• Primary Completion (ACTUAL): January 1, 2011

Study Registration Dates

• First Submitted: August 24, 2006
• First Submitted That Met QC Criteria: August 24, 2006
• First Posted (ESTIMATE): August 29, 2006

Study Record Updates

• Last Update Posted (ESTIMATE): December 11, 2013
• Last Update Submitted That Met QC Criteria: December 10, 2013
• Last Verified: December 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: NCI-2009-00163 (REGISTRY: CTRP (Clinical Trial Reporting Program)); U01CA062487 (U.S. NIH Grant/Contract); CDR0000492006; 2006-011 (OTHER: Wayne State University); 7378 (CTEP)