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

Primary Purpose

Male Breast Cancer, Recurrent Breast Cancer, Recurrent Ovarian Epithelial Cancer

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
AFP464
pharmacological study
laboratory biomarker analysis
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Male Breast Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 COHORT II (MTD) PATIENTS ONLY: 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

Sites / Locations

  • Mayo Clinic

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (AFP464)

Arm Description

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.

Outcomes

Primary Outcome Measures

Maximum tolerated dose, overall toxicity incidence, and toxicity profiles of AFP464 in the treatment of solid tumors
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.
Overall response of AFP464 in the treatment of solid tumors
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).
Time to progression
Summarized descriptively.
Time to treatment failure
Summarized descriptively.
Urinary excretion of AFP464
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.
Plasma area under the curve (AUC) of AFP464
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

Percent change in CYP1A1
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.

Full Information

First Posted
July 5, 2006
Last Updated
February 21, 2014
Sponsor
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00348699
Brief Title
AFP464 in Treating Patients With Metastatic or Refractory Solid Tumors That Cannot Be Removed By Surgery
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 Type
Interventional

2. Study Status

Record Verification Date
December 2011
Overall Recruitment Status
Completed
Study Start Date
July 2006 (undefined)
Primary Completion Date
January 2013 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

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.
Detailed Description
PRIMARY OBJECTIVES: 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
68 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (AFP464)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
AFP464
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
pharmacological study
Other Intervention Name(s)
pharmacological studies
Intervention Description
Correlative studies
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Maximum tolerated dose, overall toxicity incidence, and toxicity profiles of AFP464 in the treatment of solid tumors
Description
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.
Time Frame
28 days
Title
Overall response of AFP464 in the treatment of solid tumors
Description
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).
Time Frame
Up to 3 months
Title
Time to progression
Description
Summarized descriptively.
Time Frame
From registration to documentation of progression, assessed up to 3 months
Title
Time to treatment failure
Description
Summarized descriptively.
Time Frame
From registration to documentation of progression, unacceptable toxicity, or refusal to continue participation by the patient, assessed up to 3 months
Title
Urinary excretion of AFP464
Description
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.
Time Frame
Days 1-2, 8 and 15 of course 1
Title
Plasma area under the curve (AUC) of AFP464
Description
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.
Time Frame
Days 1-2, 8 and 15 of course 1
Secondary Outcome Measure Information:
Title
Percent change in CYP1A1
Description
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.
Time Frame
Baseline to 24 hours post AFP-464

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 COHORT II (MTD) PATIENTS ONLY: 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Matthew Goetz
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States

12. IPD Sharing Statement

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

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