AFP464 in Treating Patients With Advanced Solid Tumors - Full Text View

Sponsors and Collaborators:	Mayo Clinic National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00348699

Purpose

RATIONALE: 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.

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

Condition	Intervention	Phase
Breast Cancer Kidney Cancer Ovarian Cancer Unspecified Adult Solid Tumor, Protocol Specific	Drug: AFP464 Genetic: polymerase chain reaction Other: immunologic technique Other: laboratory biomarker analysis Other: pharmacological study Procedure: biopsy	Phase I

Study Type:	Interventional
Study Design:	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

Resource links provided by NLM:

Genetics Home Reference related topics: breast cancer

MedlinePlus related topics: Breast Cancer Cancer Kidney Cancer Ovarian Cancer

U.S. FDA Resources

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

Primary Outcome Measures:

Overall toxicity incidence and toxicity profiles as measured by dose level and tumor site via the NCI CTCAE v 3.0 [ Designated as safety issue: Yes ]
Overall response as measured by RECIST criteria every 6 weeks [ Designated as safety issue: No ]
Time to progression [ Designated as safety issue: No ]
Time to treatment failure [ Designated as safety issue: No ]
Pharmacokinetics and urinary excretion, computed and correlated with toxicity and response via Spearman correlation coefficients [ Designated as safety issue: Yes ]

Estimated Enrollment:	70
Study Start Date:	July 2006
Estimated Primary Completion Date:	May 2007 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Determine the maximum tolerated dose (MTD) of AFP464 in patients with advanced solid tumors.
Evaluate the toxicity profile of AFP464.
Characterize the plasma pharmacokinetics and urinary excretion of AFP464 and aminoflavone in these patients.
Identify any activity of AFP464 in patients with metastatic cancer.
Explore whether AFP464 induces CYP1A1 expression in tumor as measured by pre- and post-treatment tumor biopsies at the MTD as well as in peripheral lymphocytes during the dose-escalation phase and at the MTD.
Explore the relationship between the pharmacogenetic analysis and toxicity or response.

OUTLINE: This is a dose-escalation study followed by an open-label study.

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.

Cohorts of 1-6 patients receive escalating doses of AFP464 until the maximum tolerated dose (MTD) is determined.

The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. An additional 10 patients with accessible metastatic breast, renal, or ovarian cancer receive AFP464 as above at the MTD.

Blood, buccal cells, and urine are collected before beginning treatment and during course 1 and examined for biomarkers and biopharmacogenetics. Patients who are treated at the MTD also undergo biopsies before and after treatment. Samples are anlayzed via real time polymerase chain reaction (RT-PCR) and immunofluorescence.

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

PROJECTED ACCRUAL: A total of 70 patients will be accrued for this study.

Eligibility

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

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed solid tumor
- Metastatic disease refractory to available therapy OR for which no standard therapy exists
Diagnosis of breast, ovarian, or renal cell cancer (for patients treated at the maximum tolerated dose)
- Tumor amenable for paired tumor biopsies
No CNS metastases
Hormone receptor status not specified

PATIENT CHARACTERISTICS:

Male or female
ECOG performance status 0-2
Life expectancy ≥ 12 weeks
Menopausal status not specified
Absolute neutrophil count ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Hemoglobin > 9.0 g/dL
Bilirubin normal
AST and ALT ≤ 2.5 times upper limit of normal (ULN)
Creatinine ≤ 1.25 times ULN OR creatinine clearance ≥ 60 mL/min
Adequate pulmonary function, DLCO normal or asymptomatic grade 1 DLCO
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No uncontrolled 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 preclude study compliance
No seizure disorder
No history of allergic reactions attributed to compounds of similar chemical or biologic composition to AFP464
No symptomatic pulmonary disease
No active smokers or those who have smoked within the past 30 days
Willing and able to refrain completely from smoking during study treatment
Willing to provide biologic specimens (blood and urine)

PRIOR CONCURRENT THERAPY:

Recovered from prior chemotherapy
More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C) and recovered
More than 4 weeks since prior immunotherapy or biologic therapy
More than 4 weeks since prior radiotherapy
No prior thoracic radiotherapy
No prior radiotherapy to > 25% of the bone marrow
No concurrent prophylactic colony-stimulating factors
No concurrent combination antiretroviral therapy for HIV-positive patients
No concurrent participation in another study involving a pharmacologic agent (e.g., drugs, biologics, immunotherapy, or gene therapy) for symptom control or therapeutic intent
No other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00348699

Locations

United States, Minnesota
Mayo Clinic Cancer Center	Recruiting
Rochester, Minnesota, United States, 55905
Contact: Clinical Trials Office - All Mayo Clinic Locations 507-538-7623

Sponsors and Collaborators

Mayo Clinic

National Cancer Institute (NCI)

Investigators

Study Chair:

Matthew P. Goetz, MD

Mayo Clinic

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000476275, MAYO-MC0513, NCI-7380, MAYO-IAB-05-00404800, MAYO-IAB-05-00404801
Study First Received:	July 5, 2006
Last Updated:	August 4, 2009
ClinicalTrials.gov Identifier:	NCT00348699 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

unspecified adult solid tumor, protocol specific
male breast cancer
recurrent breast cancer
stage IV breast cancer

recurrent ovarian epithelial cancer
stage IV ovarian epithelial cancer
recurrent renal cell cancer
stage IV renal cell cancer

Study placed in the following topic categories:

Urinary Tract Neoplasm
Gonadal Disorders
Urogenital Neoplasms
Breast Cancer, Male
Ovarian Diseases
Urologic Neoplasms
Genital Diseases, Female
Renal Cancer
Urologic Diseases
Kidney Neoplasms
Ovarian Cancer
Kidney Diseases
Breast Diseases
Endocrine Gland Neoplasms

Kidney Cancer
Ovarian Neoplasms
Skin Diseases
Genital Neoplasms, Female
Breast Neoplasms
Endocrine System Diseases
Ovarian Epithelial Cancer
Recurrence
Carcinoma
Breast Neoplasms, Male
Carcinoma, Renal Cell
Endocrinopathy
Adenocarcinoma
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:

Ovarian Neoplasms
Neoplasms by Histologic Type
Skin Diseases
Gonadal Disorders
Genital Neoplasms, Female
Endocrine System Diseases
Breast Neoplasms
Urogenital Neoplasms
Ovarian Diseases
Urologic Neoplasms
Adnexal Diseases
Carcinoma

Genital Diseases, Female
Neoplasms
Neoplasms by Site
Urologic Diseases
Kidney Neoplasms
Carcinoma, Renal Cell
Kidney Diseases
Adenocarcinoma
Breast Diseases
Endocrine Gland Neoplasms
Neoplasms, Glandular and Epithelial

ClinicalTrials.gov processed this record on September 11, 2009