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| ID | Type | Description | Link |
|---|---|---|---|
| R01CA169336 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institutes of Health (NIH) | NIH |
| National Cancer Institute (NCI) | NIH |
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[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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Fluorothymidine F 18 PET/CT | Experimental | Fluorothymidine F 18 (FLT) PET/CT imaging ordered pre-radiation therapy, during weeks 1 and 2 of radiation therapy, and then at 1 month and 12 months after radiation therapy. The FLT PET/CT imaging ordered pre-radiation therapy is used for bone marrow sparing IMRT radiation therapy. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| fluorothymidine F 18 | Drug | 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. |
| 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 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) |
| Measure | Description | Time Frame |
|---|---|---|
| Chemotherapy Compliance | The number of participants who had chemotherapy withheld at least once for low blood counts. | At 24 months |
| Number of Participants With Standardized Toxicity Severity Grades for White Blood Cell Counts |
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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:
not pregnant (as applicable)
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| John Buatti, PhD | Department of Radiation Oncology, The University of Iowa | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Holden Comprehensive Cancer Center | Iowa City | Iowa | 52242 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21397965 | Background | 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. | |
| 21300484 | Background | 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. |
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Data are available upon request. A contract may need to be put into place, dependent upon data shared.
Upon request
Email the principal investigator for access.
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| ID | Title | Description |
|---|---|---|
| FG000 | FLT PET/CT | FLT PET/CT imaging ordered pre-radiation therapy, during weeks 1 and 2 of radiation therapy, and then at 1 month and 12 months after radiation therapy. The FLT PET/CT imaging ordered pre-radiation therapy is used for bone marrow sparing IMRT radiation therapy. 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | FLT PET/CT | FLT PET/CT imaging ordered pre-radiation therapy, during weeks 1 and 2 of radiation therapy, and then at 1 month and 12 months after radiation therapy. The FLT PET/CT imaging ordered pre-radiation therapy is used for bone marrow sparing IMRT radiation therapy. 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | All participants who received an FLT PET/CT during radiation simulation. | Posted | Mean | Standard Deviation | Percent difference (%) | Baseline (pre-treatment) |
|
Adverse events were collected for 48 hours after injection with FLT, the investigational drug under study.
Adverse events were collected through medical chart review as well as by direct contact by a licensed health provider with participant for their perceived side effects from the FLT PET/CT scan. Chart review is considered non-systematic collection; the semi-structured interview 48 hours after the scan is considered a systematic collection. Grade 0 is considered no toxicity (symptom is absent) and grade 4 is considered the most severe toxicity.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | FLT PET/CT | FLT PET/CT imaging ordered pre-radiation therapy, during weeks 1 and 2 of radiation therapy, and then at 1 month and 12 months after radiation therapy. The FLT PET/CT imaging ordered pre-radiation therapy is used for bone marrow sparing IMRT radiation therapy. 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhea, grade 1 | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| John M. Buatti, MD | The University of Iowa | 319-356-2699 | john-buatti@uiowa.edu |
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| ID | Term |
|---|---|
| D002583 | Uterine Cervical Neoplasms |
| D016889 | Endometrial Neoplasms |
| D001005 | Anus Neoplasms |
| D012004 | Rectal Neoplasms |
| D011471 | Prostatic Neoplasms |
| ID | Term |
|---|---|
| D014594 | Uterine Neoplasms |
| D005833 | Genital Neoplasms, Female |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
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| ID | Term |
|---|---|
| C002854 | alovudine |
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|
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 |
| 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 |
| 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 |
| 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 |
| 20447554 | Background | 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. |
| 27319286 | Result | 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. |
| 25207403 | Result | 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. |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
FLT PET/CT imaging ordered pre-radiation therapy to create a patient-specific bone marrow map to spare active bone marrow. |
|
|
| Secondary | Chemotherapy Compliance | The number of participants who had chemotherapy withheld at least once for low blood counts. | Posted | Count of Participants | Participants | 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 | This group includes all tumor types treated in this clinical trial and provides an overall averages. | Posted | Count of Participants | Participants | 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 | This group includes all tumor types treated in this clinical trial and provides an overall averages. | Posted | Count of Participants | Participants | 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 | This group includes all tumor types treated in this clinical trial and provides an overall averages. | Posted | Count of Participants | Participants | 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 | This group includes all tumor types treated in this clinical trial and provides an overall averages. | Posted | Count of Participants | Participants | baseline, weekly during radiation treatment for up to 5 weeks, 30 days and 1 year after treatment |
|
|
|
| 0 |
| 27 |
| 0 |
| 27 |
| 6 |
| 27 |
| Diarrhea, grade 2 | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Nausea, grade 1 | Gastrointestinal disorders | CTCAE (4.0) | Non-systematic Assessment |
|
| Headache, grade 1 | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
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| D009369 |
| Neoplasms |
| D002577 | Uterine Cervical Diseases |
| D014591 | Uterine Diseases |
| D005831 | Genital Diseases, Female |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D000091662 | Genital Diseases |
| D015179 | Colorectal Neoplasms |
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D007410 | Intestinal Diseases |
| D001004 | Anus Diseases |
| D012002 | Rectal Diseases |
| D005834 | Genital Neoplasms, Male |
| D005832 | Genital Diseases, Male |
| D011469 | Prostatic Diseases |
| D052801 | Male Urogenital Diseases |
| CTCAE grade 3 |
|
| CTCAE grade 4 (most severe) |
|
| Not assessed (test omitted) |
|
| Therapy, week 1 |
|
| Therapy, week 2 |
|
| Therapy, week 3 |
|
| Therapy, week 4 |
|
| Therapy, week 5 |
|
| 30 days post-therapy |
|
| 1 year post-therapy |
|
| CTCAE grade 3 |
|
| CTCAE grade 4 (severe toxicity) |
|
| Not assessed (test omitted) |
|
| Therapy, week 1 |
|
| Therapy, week 2 |
|
| Therapy, week 3 |
|
| Therapy, week 4 |
|
| Therapy, week 5 |
|
| 30 days post-therapy |
|
| 1 year post-therapy |
|
| CTCAE grade 3 |
|
| CTCAE grade 4 (most severe) |
|
| Not assessed (test omitted) |
|
| Therapy, week 1 |
|
| Therapy, week 2 |
|
| Therapy, week 3 |
|
| Therapy, week 4 |
|
| Therapy, week 5 |
|
| 30 days post-therapy |
|
| 1 year post-therapy |
|
| CTCAE grade 3 |
|
| CTCAE grade 4 (most severe) |
|
| Not assessed (test omitted) |
|
| Therapy, week 1 |
|
| Therapy, week 2 |
|
| Therapy, week 3 |
|
| Therapy, week 4 |
|
| Therapy, week 5 |
|
| 30 days post-therapy |
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| 1 year post-therapy |
|