FLT PET Imaging for Cervical Cancer

Study Overview
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Brief Summary
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Our primary hypothesis is that [18F]FLT PET can identify active bone marrow in addition to metabolically active tumor. This trial will use FLT-PET imaging to define areas of active bone marrow in the pelvis. The radiation plan is then designed to spare that area, in hopes of keeping the bone marrow active during therapy. Bone marrow and tumor activity will be monitored using a sequence of FLT PET scans during the course of chemotherapy and radiation therapy.

Detailed Description
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Subjects will undergo a total of up to 5 FLT PET scans. Subjects are randomized between two groups to reduce radiation exposure from the FLT PET scans. If bone marrow activity is not identified in one scan, further scans are cancelled until the 1-month follow up scan. This is not a randomization to compare therapeutic efficacy between two study arms. Data will be pooled for analysis as pre-specified in the study's statistical plan. Group 1 has FLT PET scans pretreatment, after 5 radiation treatments, after 10 radiation treatments, after 15 radiation treatments, and then 1 month after completing radiation therapy. Group 2 has FLT PET scans pretreatment, after 5 radiation treatments, after 10 radiation treatments, after 20 radiation treatments, and then 1 month after completing radiation therapy.

Official Title
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'F-18 Fluorothymidine ([18F]FLT) PET Imaging for Early Evaluation of Response to Chemoradiation Therapy in Patients With Cervical Cancer

Conditions
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Uterine Cervical Neoplasms

Intervention / Treatment
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* Drug: [F18]Fluorothymidine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability to understand and willingness to sign a written informed consent document. Histologically confirmed stage IB2, IIA, IIB, IIIB, and IVA squamous cell carcinoma of the cervix. Scheduled to receive chemo-radiation for oncologic treatment. Karnofsky of at least 60 at time of screening Life expectancy of at least 6 months. Leukocytes at least 3,000/microL absolute neutrophil count at least 1,500/microL platelets at least 100,000/microL total bilirubin at maximum 1.0 mg/dL (UIHC limit of normal) either ALT or AST less than 2.5 times the upper limit of normal creatinine less than 1.5 times the upper limit of normal non-pregnant, non-nursing, willing to use contraception Exclusion Criteria: oncology research protocol requiring full pelvic radiation (i.e., 4-field box technique) or experimental chemotherapy 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 the study requirements. subjects taking nucleoside analog medications such as those used as antiretroviral agents. patients who have undergone hysterectomy or will have a hysterectomy as part of their cancer therapy.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 2<br>Receives fourth [F18]Fluorothymidine (FLT) PET scan after 20 fractions of radiation therapy. | Drug: [F18]Fluorothymidine<br>* FLT PET scan 5 mCi (+/- 10%)<br>* Other names: FLT;|
| Experimental: Group 1<br>Receives fourth [F18]Fluorothymidine (FLT) PET scan after 15 fractions of radiation therapy. | Drug: [F18]Fluorothymidine<br>* FLT PET scan 5 mCi (+/- 10%)<br>* Other names: FLT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 dose bins 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Chemotherapy Compliance | The number of participants who missed at least one prescribed chemotherapy administration due to low blood counts. | post-treatment | 
| 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, and 30 days post treatment | 
| 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, and 30 days post treatment | 
| 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, and 30 days post treatment | 
| 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, and 30 days post treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Positron-Emission Tomography, Radiotherapy, Intensity-Modulated