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AFP464 in Treating Patients With Metastatic or Refractory Solid Tumors That Cannot Be Removed By Surgery

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00348699
Recruitment Status : Completed
First Posted : July 6, 2006
Last Update Posted : February 24, 2014
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief Summary:
This phase I trial studies the side effects and best dose of AFP464 in treating patients with metastatic or refractory solid tumors that cannot be removed by surgery. 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 or disease Intervention/treatment Phase
Male Breast Cancer Recurrent Breast Cancer Recurrent Ovarian Epithelial Cancer Recurrent Primary Peritoneal Cavity Cancer Recurrent Renal Cell Cancer Stage IV Breast Cancer Stage IV Ovarian Epithelial Cancer Stage IV Primary Peritoneal Cavity Cancer Stage IV Renal Cell Cancer Unspecified Adult Solid Tumor, Protocol Specific Drug: AFP464 Other: pharmacological study Other: laboratory biomarker analysis Phase 1

Detailed Description:


I. Determine the maximum tolerated dose (MTD) of AFP464 in patients with advanced solid tumors.

II. Evaluate the toxicity profile of AFP464. III. Characterize the plasma pharmacokinetics and urinary excretion of AFP464 and aminoflavone in these patients.

IV. Identify any activity of AFP464 in patients with metastatic cancer. V. Explore whether AFP464 induces cytochrome p450, family 1, member A1 (CYP1A1) expression in tumor (patients enrolled at the MTD) (patients enrolled at the MTD) and/or circulating tumor cells (CTCs) (dose-escalation phase and at the MTD).

VI. To explore the relationship between the pharmacogenetic analysis and toxicity or response.

OUTLINE: This is a dose-escalation study.

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

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 68 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Study Start Date : July 2006
Actual Primary Completion Date : January 2013

Arm Intervention/treatment
Experimental: Treatment (AFP464)
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.
Drug: AFP464
Given IV

Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

Other: laboratory biomarker analysis
Correlative studies

Primary Outcome Measures :
  1. Maximum tolerated dose, overall toxicity incidence, and toxicity profiles of AFP464 in the treatment of solid tumors [ Time Frame: 28 days ]
    Measured by dose level and tumor site via the NCI CTCAE v 3.0. Frequency distributions, graphical techniques and other descriptive measures will form the basis of these analyses.

  2. Overall response of AFP464 in the treatment of solid tumors [ Time Frame: Up to 3 months ]
    Measured by Modified Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Summarized by simple descriptive summary statistics delineating complete and partial responses as well as table and progressive disease in the two patient populations (overall and by tumor group).

  3. Time to progression [ Time Frame: From registration to documentation of progression, assessed up to 3 months ]
    Summarized descriptively.

  4. Time to treatment failure [ Time Frame: From registration to documentation of progression, unacceptable toxicity, or refusal to continue participation by the patient, assessed up to 3 months ]
    Summarized descriptively.

  5. Urinary excretion of AFP464 [ Time Frame: Days 1-2, 8 and 15 of course 1 ]
    Examined with descriptive summary statistics and simple graphical tools. Computed and correlated with toxicity and response via Spearman correlation coefficients for continuous variables or Wilcoxon rank sum test if one binary variable is involved.

  6. Plasma area under the curve (AUC) of AFP464 [ Time Frame: Days 1-2, 8 and 15 of course 1 ]
    Examined with descriptive summary statistics and simple graphical tools. Computed and correlated with toxicity and response via Spearman correlation coefficients for continuous variables or Wilcoxon rank sum test if one binary variable is involved.

Secondary Outcome Measures :
  1. Percent change in CYP1A1 [ Time Frame: Baseline to 24 hours post AFP-464 ]
    Computed and investigated with descriptive summary statistics and simple graphical tools. The percent change of CYP1A1 induction will also be correlated with response, toxicity, urinary excretion, and plasma pharmacokinetics measurements. circulating tumor cells (CTC) from all patients will be obtained pre- and post- infusion to determine the inducibility of gene expression of CYP1A1.

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Histologic proof of cancer that is now unresectable
  • Patients with metastatic solid tumors who are refractory to available therapy or for whom standard systemic therapy does not exist
  • Absolute neutrophil count (ANC) >= 1500/μL
  • Platelets (PLT) >= 100,000/μL
  • Total bilirubin =< upper limits of normal (ULN)
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x ULN
  • Creatinine =< 1.25 x ULN; if above 1.25 x ULN calculated creatinine clearance must be >= 60 ml/min
  • Hemoglobin (Hgb) >= 9.0 g/dl
  • Normal diffusing capacity of the lung for carbon monoxide (DLCO) or the presence of an asymptomatic grade 1 DLCO; NOTE: DLCO must be corrected for hemoglobin
  • Ability to provide informed consent
  • Willingness to return to Mayo Clinic for follow-up
  • Life expectancy >= 12 weeks
  • Willingness to provide the biologic specimens (blood and urine) as required by the protocol
  • Patients with breast, ovarian, peritoneal or renal cell carcinoma
  • Tumor that is amenable for biopsy taken during Cycle 1 at 24 +/- 4 hours following the end of AFP-464 infusion
  • International normalized ratio (INR) =< 1.4
  • Patients taking aspirin: discontinue >= 5 days prior to procedure
  • Patients receiving IV Heparin: discontinue 4 hours prior to the procedure and an APTT measurement obtained if clinically indicated
  • Patients receiving subcutaneous or low molecular weight heparin: discontinue for 8 hours prior to procedure

Exclusion Criteria:

  • Known standard therapy for the patient's disease that is potentially curative or definitely capable of extending life expectancy
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) 3 or 4
  • Prior thoracic radiotherapy
  • Symptomatic pulmonary disease
  • Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, seizure disorder, or psychiatric illness/social situations that would limit compliance with study requirements
  • Any of the following prior therapies:

    • Chemotherapy =< 4 weeks prior to study entry
    • Mitomycin C/nitrosoureas =< 6 weeks prior to study entry
    • Immunotherapy =< 4 weeks prior to study entry
    • Biologic therapy =< 4 weeks prior to study entry
    • Radiation therapy =< 4 weeks prior to study entry
    • Radiation to > 25% of bone marrow
  • Failure to fully recover from acute, reversible effects of prior chemotherapy regardless of interval since last treatment
  • Uncontrolled brain metastases; Note: Brain metastases are not permitted on study unless the metastases have been treated by surgery or radiotherapy, and the patient has been neurologically stable and off steroids for >= 4 weeks
  • Any of the following:

    • Pregnant women: Females of childbearing potential must have a negative serum pregnancy test =< 7 days prior to registration
    • Nursing women
    • Men or women of childbearing potential who are unwilling to employ adequate contraception (condoms, diaphragm, birth control pills, injections, intrauterine device [IUD], or abstinence, etc.)
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to AFP464
  • Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational (utilized for a non-FDA-approved indication and in the context of a research investigation)
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy
  • Active smokers and those who have smoked =< 30 days prior to registration, and patients unwilling or unable to refrain completely from smoking while on study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00348699

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United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
National Cancer Institute (NCI)
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Principal Investigator: Matthew Goetz Mayo Clinic

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Responsible Party: National Cancer Institute (NCI) Identifier: NCT00348699    
Other Study ID Numbers: NCI-2009-00164
NCI-2009-00164 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
MC0513 ( Other Identifier: Mayo Clinic )
7380 ( Other Identifier: CTEP )
P30CA015083 ( U.S. NIH Grant/Contract )
U01CA069912 ( U.S. NIH Grant/Contract )
First Posted: July 6, 2006    Key Record Dates
Last Update Posted: February 24, 2014
Last Verified: December 2011
Additional relevant MeSH terms:
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Breast Neoplasms
Carcinoma, Ovarian Epithelial
Carcinoma, Renal Cell
Peritoneal Neoplasms
Breast Neoplasms, Male
Neoplasms by Site
Breast Diseases
Skin Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Ovarian Neoplasms
Endocrine Gland Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Kidney Neoplasms
Urologic Neoplasms
Kidney Diseases
Urologic Diseases
Abdominal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases