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The goal of this clinical trial is to investigate the use of hypofractionated radiation (delivery of fewer but larger doses of radiation) with concurrent chemotherapy for women with metastatic of bulky uterine cervix cancer. The main questions it aims to answer are:
To confirm eligibility, within four weeks prior to study enrollment, all patients will undergo the following:
Treatment will be administered on an outpatient basis.
The main difference between the proposed regimen in the trial and standard of care is as follows:
This protocol requires photon IMRT technique followed by high dose rate (HDR) brachytherapy. The therapies use focused energy beams to kill cancer cells. Radiation therapy must be completed within 30 days +/- 2 days of initiation. Computed tomography simulation with the patient in a head-first laying on back-supine position is required. MRI-guided treatment planning and image guidance during treatment for motion management will be used.
IMRT will be given once daily Monday-Thursday, four fractions per week. The high-dose-rate (HDR) brachytherapy following institutional protocol. Brachytherapy will be delivered twice per week with a 2-day break in between sessions. A total of four brachytherapy treatments will be delivered.
After active therapy is completed, treatment-related toxicity will be assessed at the 1-month post-treatment completion visit and again at the 3-month post-treatment completion. Patients removed from the study for unacceptable adverse events will be followed until resolution or stabilization of the adverse event(s).
Routine MRI imaging to assess treatment response to radiotherapy is conducted at Day 15. Treatment response to radiotherapy followed by brachytherapy will be assessed at the 1- month and 3-months post-treatment completion.
Following the 3-months post-treatment completion, study participants will be followed for disease progression and survival status until Year 2 post-treatment initiation. NOTE: Cervical cancer patients are routinely followed (clinical surveillance) every 3-months during the first two years post-treatment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cisplatin with concurrent Intensity Modulated Radiotherapy and Brachytherapy | Experimental | Cisplatin two (2) one-time weekly intravenous infusions at 40 mg/m2 (70mg maximum) IMRT once daily, four fractions per week for 2 weeks 4.56 Gy x 8 fractions High dose rate Brachytherapy twice per week with a 2-day break in between sessions for a total of four brachytherapy treatments. The dose is 7 Gy x 4 fractions |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cisplatin | Drug | A total of two IV infusions of cisplatin will be administered on Day 1 and again on Day 8 +/- 1 day. Cisplatin starting dose is 40 mg/m2. Dose reduction is allowed (30 mg/m2) as needed for management of toxicities. |
| Measure | Description | Time Frame |
|---|---|---|
| MRI assessed rate of complete response | MRI-assessed rates of complete response as estimated by the number of CRs (complete response per RECIST v1.1) divided by the total number of evaluable subjects | 1 month post treatment (day 60) |
| Measure | Description | Time Frame |
|---|---|---|
| MRI assessed rate of complete response | The proportion of complete response will be assessed at 3-mos post-treatment completion, i.e., Day 120, as estimated by the number of CRs (complete response per RECIST v1.1) divided by the total number of evaluable subjects. | 3 months post treatment (day 120) |
| progression-free survival (PFS) |
| Measure | Description | Time Frame |
|---|---|---|
| Change in levels of uterine cervix cancer circulating tumor cells | A total of 15mL of peripheral venous blood will be collected for Circulating tumor cells (CTC). Counts will be reported as means with standard deviations in tabular format | pre-treatment; 1-month post-treatment completion (Day 60); and 3-mos post-treatment completion (Day 120) |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Yvonne Taul, RN | Contact | 859-323-2354 | yvonne.taul@uky.edu | |
| Denise Fabian, MD | Contact |
| Name | Affiliation | Role |
|---|---|---|
| Denise Fabian, MD | University of Kentucky | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Markey Cancer Center | Recruiting | Lexington | Kentucky | 40506 | United States |
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| ID | Term |
|---|---|
| D002583 | Uterine Cervical Neoplasms |
| D014594 | Uterine Neoplasms |
| ID | Term |
|---|---|
| D005833 | Genital Neoplasms, Female |
| D014565 | Urogenital Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| D002945 | Cisplatin |
| D050397 | Radiotherapy, Intensity-Modulated |
| D001918 | Brachytherapy |
| ID | Term |
|---|---|
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
| D017672 | Nitrogen Compounds |
| D017671 | Platinum Compounds |
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|
| intensity modulated radiation therapy (IMRT) | Radiation | given once daily Monday-Thursday, four fractions per week for 2 weeks. The radiation dose is 4.56 Gy x 8 fractions. |
|
| high-dose-rate (HDR) brachytherapy | Radiation | administered 2x weekly (allow at least 72-hours window between sessions); weekdays only for 2 weeks. The radiation dose is 7 Gy x 4 fractions. |
|
Progression-free survival (PFS) is calculated from the date of treatment start (week 1, day 1) to the date of initial disease progression or to the date of death or to 2-years post-treatment initiation, whichever occurs first. |
| up to 2 years |
| overall survival (OS) | Overall Survival is calculated from the date of treatment start until date of death or up to 2-years post-treatment initiation, whichever occurs first. | up to 2 years |
| Treatment Completion | reported as a proportion of subjects who complete entire prescribed course of the treatment based on the treatment compliance for Radiotherapy and for Cisplatin | up to 32 days |
| Treatment Tolerability | Assessed by Common Terminology Criteria for Adverse Events (CTCAE v4.0) | up to 2 years |
| 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 |
| D020266 |
| Radiotherapy, Conformal |
| D011881 | Radiotherapy, Computer-Assisted |
| D011878 | Radiotherapy |
| D013812 | Therapeutics |