Male Breast CancerPhase 1NCT00348699
AFP464 in Treating Patients With Metastatic or Refractory Solid Tumors That Cannot Be Removed By Surgery
A Phase 1 study testing AFP464, pharmacological study and laboratory biomarker analysis in people with Male Breast Cancer and Recurrent Breast Cancer, run by National Cancer Institute (NCI) at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Male Breast Cancer, Recurrent Breast Cancer, Recurrent Ovarian Epithelial Cancer
- What is being tested?
- AFP464, pharmacological study and laboratory biomarker analysis
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 68 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2006to Jan 2013
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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:
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- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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.
- Conditions
- Male Breast Cancer, Recurrent Breast Cancer, Recurrent Ovarian Epithelial Cancer, Recurrent Primary Peritoneal Cavity Cancer, Recurrent Renal Cell Cancer, Stage IV Breast Cancer
- Being tested
- AFP464, pharmacological study, laboratory biomarker analysis
- Medical subject headings
- Breast Neoplasms, Male, Breast Neoplasms, Carcinoma, Ovarian Epithelial, Carcinoma, Renal Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AFP464Drug
Given IV
Also called pharmacological studies
Correlative studies
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (AFP464) | Experimental | 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. Receives: Drug: AFP464; Other: pharmacological study; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 28 days
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).
Measured: Up to 3 months
Time to progression
Summarized descriptively.
Measured: From registration to documentation of progression, assessed up to 3 months
Time to treatment failure
Summarized descriptively.
Measured: From registration to documentation of progression, unacceptable toxicity, or refusal to continue participation by the patient, assessed up to 3 months
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.
Measured: Days 1-2, 8 and 15 of course 1
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.
Measured: Days 1-2, 8 and 15 of course 1
Secondary outcomes (1)
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.
Measured: Baseline to 24 hours post AFP-464
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jul 2006 (estimated)
- Study startJul 2006
- Primary completionJan 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Male Breast CancerStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 68 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Matthew Goetz, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00348699
- Sponsor's protocol ID
- NCI-2009-00164
- Other IDs
- NCI-2009-00164, MAYO-IAB-05-00404800, MAYO-IAB-05-00404801, NCI-7380, CDR0000476275, MAYO-MC0513, MC0513, 7380
- Status last verified
- Dec 2011
- First submitted
- 5 Jul 2006
- Last updated
- 24 Feb 2014
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00348699
- Acronym / sponsor ID
- NCI-2009-00164
- Conditions
- Male Breast Cancer, Recurrent Breast Cancer, Recurrent Ovarian Epithelial Cancer, Recurrent Primary Peritoneal Cavity Cancer, Recurrent Renal Cell Cancer, Stage IV Breast Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 68 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Jul 2006
- Primary completion
- Jan 2013 (actual)
- First posted
- 6 Jul 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (AFP464) | Experimental | Drug: AFP464, Other: pharmacological study, Other: laboratory biomarker analysisPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- 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)
Key exclusion criteria (23 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AFP464Given IV | Drug | Treatment (AFP464) |
| pharmacological studyAlso: pharmacological studiesCorrelative studies | Other | Treatment (AFP464) |
| laboratory biomarker analysisCorrelative studies | Other | Treatment (AFP464) |
Primary outcome
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.
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).
Time to progression
Time frame: From registration to documentation of progression, assessed up to 3 months
Summarized descriptively.
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.
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.
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.
1 secondary outcome
Percent change in CYP1A1
Time frame: Baseline to 24 hours post AFP-464
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2014.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Matthew Goetz principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AFP464, pharmacological study and laboratory biomarker analysis in people with Male Breast Cancer and Recurrent Breast Cancer, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 20 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Feb 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerated dose, overall toxicity incidence, and toxicity profiles of AFP464 in the treatment of solid tumors (time frame: 28 days). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Feb 2014.