Bone Marrow Sparing Image-Guided Radiation Therapy (RT) Incorporating Novel Use of GCSF and FDG-PET Imaging

Study Overview
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Brief Summary
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This is a research study using Granulocyte Colony Stimulating Factor (GCSF) as a bone marrow stimulating agent for imaging to guide radiation treatment planning. G-CSF is a type of growth factor. Growth factors are proteins made in the body. G-CSF is a type of growth factor that makes the bone marrow produce white blood cells to reduce the risk of infection after some types of cancer treatment.

Detailed Description
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This is a phase 1 and 2 study. The phase I is a dose finding portion of the study and phase 2 will enroll additional patients at the dose found in phase I. Patients in phase I and phase 2 will have the same treatment and followup. Participants will undergo standard of care diagnostic imaging, complete blood count (CBC) with differential and chemistry labs initially. While receiving the GCSF, participants will have a CBC with differential checked a day after each dose and one day prior to first day of radiation. The treatment planning FDG PET/CT will be performed shortly after the GCSF. During chemoradiation, participants will have weekly CBC with differential checked and other labs as standard of care.

Official Title
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Phase 1 2 Study of Individualized Bone Marrow Sparing Image Guided Radiotherapy Incorporating Novel Use of Granulocyte Colony Stimulating Factor and FDG PET Imaging

Conditions
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Cervix Cancer, Endometrial Cancer

Intervention / Treatment
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* Diagnostic Test: FDG PET/CT
* Drug: GCSF


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 2018 international Federation of Gynecology and Obstetrics (FIGO) stage I IIIC1 cervix cancer with no prior treatment or stage IIIA IIIC1 endometrial cancer status post hysterectomy and lymph node assessment No required para aortic or extended field radiation Eastern Cooperative Oncology Group (ECOG) performance status 0 2 Adequate kidney function (serum Cr <1.5 or creatinine clearance >50 mg/dl) Adequate bone marrow function (white blood cells > 3.0 X 109/L, platelets >100 x 109/L) Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: Treatment for other cancer in the past 2 years Previous pelvic radiation Medical condition that prevents receiving chemotherapy

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: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase I -Dose finding, Cohort 1<br>Dosing will occur in cohorts of 4 patients with the start at dose of GCSF will be 780 mcg x 3 days | Diagnostic Test: FDG PET/CT<br>* Fluorodeoxyglucose (FDG)-positron emission tomography (PET) and computed tomography (CT)<br>Drug: GCSF<br>* Granulocyte Colony Stimulating Factor (GCSF)<br>* Other names: G-CSF;|
| Experimental: Phase I -Dose finding, Cohort 2<br>Dosing will occur in cohorts of 4 patients, If 4 out of 4 patients achieve the target SUVmean, the GCSF dose will be 780 mcg x 2 days | Diagnostic Test: FDG PET/CT<br>* Fluorodeoxyglucose (FDG)-positron emission tomography (PET) and computed tomography (CT)<br>Drug: GCSF<br>* Granulocyte Colony Stimulating Factor (GCSF)<br>* Other names: G-CSF;|
| Experimental: Phase I -Dose finding, Cohort 3<br>Dosing will occur in cohorts of 4 patients, If 4 out of 4 patients achieve the target SUVmean, the GCSF dose will be 780 mcg x 1 day | Diagnostic Test: FDG PET/CT<br>* Fluorodeoxyglucose (FDG)-positron emission tomography (PET) and computed tomography (CT)<br>Drug: GCSF<br>* Granulocyte Colony Stimulating Factor (GCSF)<br>* Other names: G-CSF;|
| Experimental: Phase II-G-CSF<br>Phase 2 participants will be treated with the optimal dose of GCSF found in the phase 1 portion of the study. | Diagnostic Test: FDG PET/CT<br>* Fluorodeoxyglucose (FDG)-positron emission tomography (PET) and computed tomography (CT)<br>Drug: GCSF<br>* Granulocyte Colony Stimulating Factor (GCSF)<br>* Other names: G-CSF;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the Recommended phase 2 dose (RP2D) | Recommended phase 2 dose (RP2D) will be defined as the dose at which the standard uptake value (SUV) on D5 FDG PET reaches target SUVmean of 2.5 or higher with normalization of white blood cells (WBC) and ANC prior to start of radiation. | 12 months | 
| Determine the rate of grade 3 or greater neutropenia (ANC < 1000/mm3 at any point of therapy) | Rate of grade 3 or greater neutropenia (ANC < 1000/mm3 at any point of therapy) will be monitored by the regular CBC with differential on the study schema and calendar, as per standard of care for patients receiving chemoradiation and/or chemotherapy. | 33 months |