A Pilot Study of F-18 Paclitaxel (FPAC) PET for Evaluating Drug Delivery of Solid Tumors in Breast, Lung, Renal, and Adrenal Cancers - NCT01086696-20892(Clinical Trial 568124)
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| City: |
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Bethesda |
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State:
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MD |
| Zip Code: |
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20892 |
| Conditions: |
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Breast Cancer - Lung Cancer - Renal Cancer - Adrenal Cancer |
| Purpose: |
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Background:
- Paclitaxel is a chemotherapy drug that is commonly used to treat different types of
cancers. However, cancer tumors can become resistant to paclitaxel, and as a result
they will fail to accumulate sufficient concentrations of paclitaxel to kill the cancer
cells. Researchers are interested in studying whether tumors have become resistant to
paclitaxel, but to do so it must be possible to see how much paclitaxel is absorbed by
the tumor cells.
- 18F-Fluoropaclitaxel (FPAC) is a form of paclitaxel that has been modified to be
slightly radioactive in order to show up on positron emission tomography (PET) scans.
By injecting a very small amount (much less that that used to treat tumors) of the
radiolabeled drug into the body, researchers hope to use PET scans to evaluate the
amount of the drug absorbed by solid tumors. Because FPAC is best used to study tumors
located above the diaphragm, all subjects in the study will have tumors near or above
the diaphragm.
Objectives:
- To determine the safety and effectiveness of FPAC as a radiological evaluation chemical.
Eligibility:
- Individuals at least 18 years of age who have been diagnosed with breast, adrenal, renal,
or lung cancer and have a tumor located someone in the body at least 1 centimeter above the
diaphragm.
Design:
- Participants will be screened with a physical exam, blood tests, and imaging studies as
directed by the study researchers.
- Participants will receive a single dose of FPAC, followed by a series of PET scans.
Regular scans will be performed for 3 hours after the dose of FPAC.
- Participants will also have a single dose of a more conventional radiotracer, followed
by a series of PET scans. The results of the two sets of scans will be compared with
information from previous imaging studies of participants' tumors....
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| Study summary: |
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BACKGROUND:
- Paclitaxel is a commonly used chemotherapeutic to which tumors can become resistant by
failing to accumulate sufficient concentrations of the agent to be lethal to the cell.
- A noninvasive imaging test could determine the uptake of paclitaxel by tumors
- The ability to non-invasively predict chemotherapeutic uptake in solid tumors could
help select patients likely to respond to treatment, estimate drug concentration within
the tumor and possibly aid in the development improved of drug delivery systems and
drug resistance evasion strategies.
- The PET department at the NIH developed an efficient procedure for fluorination of
paclitaxel to [18F]-labeled paclitaxel (FPAC) and studied its biodistribution in rats
and mice.
- Initial preclinical data shows the biodistribution of FPAC to be similar to that of
paclitaxel. It is proposed that the uptake kinetics of FPAC in vivo using PET imaging
will be representative of the uptake kinetics of paclitaxel.
- First in human studies were performed by the PI (Kurdziel, KA) while at Virginia
Commonwealth University, Richmond VA in three normal volunteers and three breast cancer
patients with no adverse events. Human dosimetry estimates were obtained.
- PET/CT imaging with FPAC should permit quantitation of solid tumor uptake of the agent,
which in turn should parallel paclitaxel solid tumor kinetics.
- The physiological distribution of the agent limits its use below the diaphragm. Thus,
lung and breast cancers, which tend to be sensitive to taxanes, are the target tumors
in this study. Adrenal and renal tumors, which tend to be insensitive to taxanes are
being included as negative-control tumors.
PRIMARY OBJECTIVES:
- Determine if the FPAC uptake in tumors is different than the uptake in normal
background tissues
- Determine safety of FPAC administration
SECONDARY OBJECTIVES:
- Compare FPAC uptake with FDG uptake in solid tumors
- Make preliminary comparisons of FPAC uptake with treatment response and drug
transporter expression when available
ELIGIBILITY:
- Subjects must be 18 years or older for inclusion in this study
- Subjects must have histologically proven breast, adrenal, renal or lung cancer with a
lesion above the diaphragm greater than or equal to 1cm
- Subjects may not receive any other investigational agents 24 hours before or following
FPAC injection.
- Subjects must have an ECOG performance status less than or equal to 2 (Karnofsky
greater than or equal to 60%)
- Subjects must NOT be pregnant
- A documented history of prior chemotherapy and radiation therapy and responses to those
treatments must be available.
DESIGN:
In this protocol, we plan to stratify enrollment into 2 groups, enrolling 15 subjects in
each arm: subjects with tumor type historically sensitive to paclitaxel therapy (lung and
breast cancers) and subjects with tumor generally not responsive to paclitaxel therapy
(adrenal and renal). Subjects will undergo dynamic FPAC PET/CT imaging and baseline FDG
PET/CT. Subject is then expected to progress to standard or investigational treatment (not
defined by this protocol). Data regarding clinical and or imaging response to therapy will
be collected if available. If a previous biopsy specimen is available, IHC for known drug
transporters will also be performed. |
| Criteria: |
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- INCLUSION CRITERIA:
- Subjects must have a history of histologically or cytologically confirmed breast,
lung, adrenal or renal cancer with a tumor above the diaphragm greater than or equal
to 1 cm
- Subjects must be 18 years or older for inclusion in this study.
- Subjects must sign a written informed consent document and in accordance with
institutional guidelines.
- If female, the subject must be postmenopausal for a minimum of two years, be
surgically sterile, or have a negative pregnancy test within the 24 hours prior to
tracer injection
- There are no study related limitations regarding previous radiation or chemotherapy.
- Subjects must have an ECOG performance status less than or equal to 2 (Karnofsky
greater than or equal to 60%)
- Subjects must have normal organ and marrow function as defined below:
- leukocytes greater than or equal to 3,000/mcL
- absolute neutrophil count greater than or equal to 1,500/mcL
- platelets greater than or equal to 100,000/mcL
- total bilirubin within less than or equal to 2.5 times institutional limits OR < 3.0
mg/dl in patients with Gilbert's syndrome
- AST(SGOT)/ALT(SGPT) less than or equal to 2.5 times the institutional upper limit of
normal (< 5 times the ULN for patients with known hepatic metastases)
- creatinine within normal institutional limits OR, for patients with creatinine levels
above institutional normal, creatinine clearance greater than or equal to 60
mL/min/1.73 m(2).
- A documented history of prior chemotherapy and radiation therapy and responses to
those treatments must be available.
EXCLUSION CRITERIA:
- Subjects may not receive any other investigational agents 24 hours prior to or
following FPAC injection
- Subjects must NOT receive radiation therapy to the target lesion less than or equal
to 8 weeks prior to FPAC injection
- Subjects must NOT have had surgery near the target lesion less than or equal to 4
weeks prior to FPAC injection
- Subjects with a history of allergic reactions attributed to compounds of similar
chemical or biologic composition to F-18 fluoropaclitaxel (i.e. Taxol)
- Subjects with severe claustrophobia (not relieved by oral anxiolytics) or other
condition that would make them unable to lie still for the duration of the study
- Subjects with uncontrolled intercurrent illness or psychiatric illness/social
situations that would limit compliance with study requirements
- Subjects who are pregnant or lactating or who suspect they might be pregnant. Because
there is an unknown but potential risk for adverse events in nursing infants
secondary to treatment of the mother with FPAC, breastfeeding should be discontinued
if the mother receives FPAC. |
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| Study is available at: |
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National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, MD 20892
United States
Primary Contact:
NCI Referral Office
Email: ncicssc@mail.nih.gov
Phone: 1-888-NCI-1937 |
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If you are interested in this clinical trial please use the contact information above. If you would like to get additional information about this clinical trial please visit ClinicalTrials.gov.
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| Data Source: |
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ClinicalTrials.gov |
| Date Processed: |
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March 23, 2011 |
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