Clinical trial NCT01717391: [F-18] Fluorothymidine PET/CT Imaging for Pelvic Cancers
Official title: Improving Pelvic Cancer Patient Chemoradiotherapy Outcomes With FLT PET Imaging
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Uterine Cervical Neoplasms
Endometrial Neoplasms
Anus Neoplasms
Rectal Neoplasms
Prostatic Neoplasms
Keywords: radiotherapy
Positron-Emission Tomography and Computed Tomography
chemotherapy
bone marrow
Lead sponsor: University of Iowa
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Cancer Institute (NCI)
First posted: 2012-10-30
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percent Difference From Baseline IMRT Plan (%)
timeFrame: Baseline (pre-treatment)
Secondary outcomes:
measure: Chemotherapy Compliance
timeFrame: At 24 months
measure: Number of Participants With Standardized Toxicity Severity Grades for White Blood Cell Counts
timeFrame: baseline, weekly during radiation treatment for up to 5 weeks, 30 days and 1 year after treatment
measure: Number of Participants With Standardized Toxicity Severity Grades for Decreased Platelet Counts.
timeFrame: baseline, weekly during radiation treatment for up to 5 weeks, 30 days and 1 year after treatment
measure: Number of Participants With Standardized Toxicity Severity Grades for Decreased Absolute Neutrophil Counts (ANCs)
timeFrame: baseline, weekly during radiation treatment for up to 5 weeks, 30 days and 1 year after treatment
measure: Number of Participants With Standardized Toxicity Severity Grades for Decreased Lymphocyte Counts.
timeFrame: baseline, weekly during radiation treatment for up to 5 weeks, 30 days and 1 year after treatment
Other outcomes:
Locations:
city: Iowa City
country: United States
facility: Holden Comprehensive Cancer Center
state: Iowa
Study officials:
affiliation: Department of Radiation Oncology, The University of Iowa
name: John Buatti, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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.
citation: McGuire SM, Menda Y, Boles Ponto LL, Gross B, Buatti J, Bayouth JE. 3'-deoxy-3'-[(1)(8)F]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.
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.
citation: 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 Chemoradiation Therapy for Pelvic Cancer Patients. Int J Radiat Oncol Biol Phys. 2016 Sep 1;96(1):228-39. doi: 10.1016/j.ijrobp.2016.04.009. Epub 2016 Apr 19.
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.