[F-18] Fluorothymidine PET/CT Imaging for Pelvic Cancers

Prostatic Neoplasms Clinical Trial

Official title:

Improving Pelvic Cancer Patient Chemoradiotherapy Outcomes With FLT PET Imaging

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01717391
• Other study ID #: 201204712
• Secondary ID: R01CA169336
• Status: Completed
• Phase: Phase 2
• Start date: October 1, 2012
• Est. completion date: April 30, 2017

Study information

• Verified date: March 2019
• Source: University of Iowa
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

[F-18] Fluorothymidine PET imaging will be used to create a radiation therapy treatment plan to avoid active bone marrow in the pelvis. This will be done to evaluate if sparing bone marrow will help maintain blood counts. This would impact chemotherapy administration.

Description:

Overall survival of pelvic cancer patients depends on control of systemic disease. If local radiation therapy depletes bone marrow function to such an extent that systemic therapies must be withheld, chances of metastatic failure increase significantly. This may be more significant for this group of patients because approximately one third of adult bone marrow is located in the pelvic region. Strategies to minimize toxicities would benefit a range of pelvic cancer patients including gynecologic, anal, rectal, and prostate. New chemoradiation combinations improve outcomes for these disease sites, but come at the cost of higher levels of toxicity. As many as 40% of cervical cancer patients miss at least one chemotherapy cycle due to hematologic toxicity and 36% of anal cancer patients experience grade 3 or 4 hematologic toxicity when undergoing chemoradiation therapy. A clinical trial of concurrent chemoradiation therapy for rectal cancer was terminated due to toxicity, including hematologic toxicities. Concurrent chemoradiation therapy shows promise for advanced stage prostate cancers, but it also increases grade 3 and 4 toxicities. To successfully limit hematologic toxicities for pelvic cancers, it is extremely advantageous to avoid irradiating the highly proliferative compartments of the pelvic bone marrow. However, the complex structure of the pelvis makes it difficult to assess the efficacy of radiation therapy (RT) planning strategies to avoid areas critical to hematopoiesis. Uptake of [18F]fluorothymidine imaged with positron emission tomography (FLT PET/CT) can be an accurate and sensitive tool for identifying and monitoring the effects of chemoradiation on proliferative pelvic bone marrow. Clinically validating the utility of FLT PET/CT imaging for identifying active bone marrow in the design of bone marrow sparing RT-plans and the important bone marrow assessment time points would provide a method to reduce acute and chronic hematologic toxicities for pelvic cancer patients.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: April 30, 2017
• Est. primary completion date: February 29, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Ability to understand and willingness to sign a written informed consent document.

• Recommended to undergo pelvic irradiation with concurrent chemotherapy.

• At least 18 years of age. Pediatrics would be best served by a protocol designed for their specific needs.

• Karnofsky Performance Status of at least 60% at time of screening.

• Life expectancy of greater than 6 months.

• Subject must have normal organ and marrow function (as defined below) within 30 days of study enrollment:

• leukocytes at least 3,000 / µL

• absolute neutrophil count of at least 1500 / µL

• platelets of at least 100,000 / µL

• creatinine equal to or less than the upper limit of normal

• not pregnant (as applicable)

Exclusion Criteria:

• history of allergic reactions attributed to compounds of similar chemical or biologic composition to FLT

• an oncology research protocol requiring full pelvic radiation (i.e., 4 field box technique)

• uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

• subjects taking nucleoside analog medications such as those used as antiretroviral agents.

Related Conditions & MeSH terms

• Anus Neoplasms
• Endometrial Neoplasms
• Neoplasms
• Pelvic Neoplasms
• Prostatic Neoplasms
• Rectal Neoplasms
• Uterine Cervical Neoplasms

Intervention

Drug:
• fluorothymidine F 18
A patient-specific bone marrow map will be designed from the pre-therapy FLT PET/CT imaging. A highly conformal radiation plan will be designed to spare active bone marrow.

Locations

Country	Name	City	State
United States	Holden Comprehensive Cancer Center	Iowa City	Iowa

Sponsors (3)

Lead Sponsor	Collaborator
John M. Buatti	National Cancer Institute (NCI), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

References & Publications (5)

McGuire SM, Bhatia SK, Sun W, Jacobson GM, Menda Y, Ponto LL, Smith BJ, Gross BA, Bayouth JE, Sunderland JJ, Graham MM, Buatti JM. Using [(18)F]Fluorothymidine Imaged With Positron Emission Tomography to Quantify and Reduce Hematologic Toxicity Due to Che — View Citation

McGuire SM, Menda Y, Boles Ponto LL, Gross B, Buatti J, Bayouth JE. 3'-deoxy-3'-[¹8F]fluorothymidine PET quantification of bone marrow response to radiation dose. Int J Radiat Oncol Biol Phys. 2011 Nov 1;81(3):888-93. doi: 10.1016/j.ijrobp.2010.12.009. Epub 2011 Feb 6. Erratum in: Int J Radiat Oncol Biol Phys. 2012 Sep 1;84(1):7. — View Citation

McGuire SM, Menda Y, Ponto LL, Gross B, Juweid M, Bayouth JE. A methodology for incorporating functional bone marrow sparing in IMRT planning for pelvic radiation therapy. Radiother Oncol. 2011 Apr;99(1):49-54. doi: 10.1016/j.radonc.2011.01.025. Epub 2011 Mar 22. — View Citation

McGuire SM, Menda Y, Ponto LLB, Gross B, TenNapel M, Smith BJ, Bayouth JE. Spatial mapping of functional pelvic bone marrow using FLT PET. J Appl Clin Med Phys. 2014 Jul 8;15(4):129–136. doi: 10.1120/jacmp.v15i4.4780. — View Citation

Menda Y, Ponto LL, Dornfeld KJ, Tewson TJ, Watkins GL, Gupta AK, Anderson C, McGuire S, Schultz MK, Sunderland JJ, Graham MM, Buatti JM. Investigation of the pharmacokinetics of 3'-deoxy-3'-[18F]fluorothymidine uptake in the bone marrow before and early after initiation of chemoradiation therapy in head and neck cancer. Nucl Med Biol. 2010 May;37(4):433-8. doi: 10.1016/j.nucmedbio.2010.02.005. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Difference From Baseline IMRT Plan (%)	The difference in volume of bone marrow receiving radiation using a bone-marrow-sparing radiation plan compared to a standard radiation plan (IMRT), expressed as a percentage. Both plans are patient-specific. Bone-marrow is identified using the baseline FLT PET/CT obtained pre-imaging. Active bone marrow is considered to have an uptake value (SUV) of 2, 3, or 4. The standard IMRT plan was created using the criteria of the National Cancer Institute's Radiation Therapy Oncology Group study RTOG-0418. Radiation doses evaluated are 5 Gray, 10 Gray, 20 Gray, and 30 Gray. The change in dose to tumor is also provided. A negative value indicates that more bone marrow or tissue was spared using the bone-marrow sparing plan.	Baseline (pre-treatment)
Secondary	Chemotherapy Compliance	The number of participants who had chemotherapy withheld at least once for low blood counts.	At 24 months
Secondary	Number of Participants With Standardized Toxicity Severity Grades for White Blood Cell Counts	White blood cell counts measurements expressed in standardized toxicity severity grades (Common Terminology Criteria for Adverse Events, v4.03) measured weekly during combined chemotherapy and radiation therapy treatment and then once at 30 day follow-up and at 1 year follow-up	baseline, weekly during radiation treatment for up to 5 weeks, 30 days and 1 year after treatment
Secondary	Number of Participants With Standardized Toxicity Severity Grades for Decreased Platelet Counts.	Platelet cell counts measurements expressed in standardized toxicity severity grades (Common Terminology Criteria for Adverse Events, v4.03) measured once weekly during combined chemotherapy and radiation therapy, then once at 30 day follow-up, and once at 1 year follow-up	baseline, weekly during radiation treatment for up to 5 weeks, 30 days and 1 year after treatment
Secondary	Number of Participants With Standardized Toxicity Severity Grades for Decreased Absolute Neutrophil Counts (ANCs)	Absolute neutrophil counts (ANCs) measurements expressed in standardized toxicity severity grades (Common Terminology Criteria for Adverse Events, v4.03) measured once weekly during combined chemotherapy and radiation therapy, then once at 30 day follow-up, and once at 1 year follow-up	baseline, weekly during radiation treatment for up to 5 weeks, 30 days and 1 year after treatment
Secondary	Number of Participants With Standardized Toxicity Severity Grades for Decreased Lymphocyte Counts.	Lymphocyte counts measurements expressed in standardized toxicity severity grades (Common Terminology Criteria for Adverse Events, v4.03) measured once weekly during combined chemotherapy and radiation therapy, then once at 30 day follow-up, and once at 1 year follow-up	baseline, weekly during radiation treatment for up to 5 weeks, 30 days and 1 year after treatment