A Pilot Study of F-18 Paclitaxel (FPAC) PET for Evaluating Drug Delivery of Solid Tumors in Breast, Lung, Renal, and Adrenal Cancers
- 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.
- To determine the safety and effectiveness of FPAC as a radiological evaluation chemical.
- 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.
- 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....
Drug: F-18 Paclitaxel (FPAC)
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Diagnostic
|Official Title:||A Pilot Study of F-18 Paclitaxel (FPAC) PET for Evaluating Drug Delivery of Solid Tumors in Breast, Lung, Renal, and Adrenal Cancers|
- Determine if the FPAC uptake in tumors is different than the uptake in normal background tissues; Determine safety of FPAC administration
- Compare FPAC uptake with FDG uptake in solid tumors; make preliminary comparisons of FPAC uptake with treatment response and drug transporter expression when available
|Study Start Date:||March 2010|
|Estimated Study Completion Date:||January 2015|
|Estimated Primary Completion Date:||January 2015 (Final data collection date for primary outcome measure)|
Drug: F-18 Paclitaxel (FPAC)
- 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.
- Determine if the FPAC uptake in tumors is different than the uptake in normal background tissues
- Determine safety of FPAC administration
- 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 outside of the abdomen and pelvis 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
- When applicable, a documented history of prior chemotherapy and radiation therapy and responses to those treatments must be available.
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 regional dynamic FPAC PET/CT followed by static whole body imaging. All participants will undergo FDG PET/CT (outside studies permitted if submitted in DICOM format) Follow-up FDG PET/CT may be performed. (following at least 1 cycle of therapy), if applicable. If the target lesion is surgically resected, the post-treatment scan will not be performed. Subject is then expected to progress to standard or investigational therapeutic intervention (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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01086696
|Contact: Yolanda McKinney, R.N.||(301) email@example.com|
|Contact: Karen A Kurdziel, M.D.||(301) firstname.lastname@example.org|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office (888) NCI-1937|
|Principal Investigator:||Karen A Kurdziel, M.D.||National Cancer Institute (NCI)|