Trial record 6 of 10321 for:    NCI

AFP464 in Treating Patients With Advanced Solid Tumors

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00369200
First received: August 24, 2006
Last updated: December 10, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Unspecified Adult Solid Tumor, Protocol Specific
Drug: AFP464
Other: laboratory biomarker analysis
Other: pharmacological study
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 Study of AFP464 (Aminoflavone Prodrug) in Patients With Advanced Solid Tumors

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Maximum tolerated dose determined by dose-limiting toxicity [ Time Frame: 28 days ] [ Designated as safety issue: Yes ]
  • Types and grades of toxicity [ Time Frame: Up to 4 weeks ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Pharmacokinetic, pharmacodynamic, and pharmacogenomic parameters [ Time Frame: Up to 4 weeks ] [ Designated as safety issue: No ]
  • Response rate [ Time Frame: Up to 4 weeks ] [ Designated as safety issue: No ]
    Point and exact confidence interval estimates of response rate will be provided for all eligible patients combined, and if warranted, by specific dose levels.


Enrollment: 60
Study Start Date: June 2006
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United States, Michigan
Wayne State University
Detroit, Michigan, United States, 48202
Sponsors and Collaborators
Investigators
Principal Investigator: Patricia LoRusso Wayne State University
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00369200     History of Changes
Other Study ID Numbers: NCI-2009-00163, NCI-2009-00163, CDR0000492006, 2006-011, 7378, U01CA062487
Study First Received: August 24, 2006
Last Updated: December 10, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Neoplasms

ClinicalTrials.gov processed this record on August 28, 2014