Clear Cell Endometrial Cancer, Endometrial Cancer, Papillary Serous
Conditions
Keywords
Endometrial Cancer, Gynecologic Cancer, radiation therapy
Brief summary
The purpose of this study is to determine the feasibility of treatment in patients with high risk endometrial cancer treated by vaginal cuff brachytherapy followed by 3 cycles of dose dense paclitaxel and carboplatin chemotherapy.
Detailed description
Before the patient begins the study: Endometrial cancer is commonly treated with surgery. The patient must have already had surgery including hysterectomy (removal of the uterus) prior to being considered eligible for this study. The surgery may also include removal of pelvic and para-aortic lymph nodes. Following the surgery, the doctor will identify if the patient has factors related to the cancer which places the patient at a greater risk for the cancer returning. Prior to participating in this study there are exams, tests or procedures to find out if the patient can be treated in the study. Most are part of regular cancer care. Treatment: All patients will receive radiation therapy followed by three cycles of dose dense paclitaxel and carboplatin chemotherapy. Radiation therapy will be delivered either by LDR or HDR brachytherapy and must be specified at the time of enrollment. The vaginal brachytherapy should be started within 12 weeks of surgery (within 2 weeks of enrollment). Chemotherapy should start within 3 weeks of initiating brachytherapy. Study participation will be up to two years.
Interventions
RADIATIONVaginal Cuff Brachytherapy
Within 12 weeks of surgery. Either LDR or HDR brachytherapy will be permitted
DRUGCarboplatin
Carboplatin IV on day 1 of a 21 day cycle for 3 cycles
DRUGPaclitaxel
Paclitaxel IV on days 1,8 and 15 of a 21 day cycle for 3 cycles
Sponsors
University of Oklahoma
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
1. All patients must have undergone hysterectomy. Bilateral salpingooophorectomy is strongly encouraged but not mandatory. 2. Pelvic and para-aortic lymphadenectomy are optional, but strongly encouraged. Peritoneal washing are optional. 3. If either a bilateral salpingo-oophorectomy or nodal dissection was not performed, post-operative pre-treatment CT/MRI is required and must not demonstrate evidence suggestive of metastatic disease (adnexa, nodes, intraperitoneal disease). Post-operative, pre-treatment CT/MRI must be performed if a pelvic and para-aortic nodal dissection was not performed. 4. All patients will be staged according to the FIGO 2009 staging system and with endometrial carcinoma (endometrioid types) confined to the corpus uteri or with endocervical glandular involvement fitting one of the following high-intermediate risk factor categories: * age ≥18 years with 3 risk factors * Risk factors: 1. Grade 2 or 3 tumor, (+) lymphovascular space invasion, outer ½ myometrial invasion. Patients with these risk criteria may be enrolled with either positive or negative cytology. 2. Patients with Stage II endometrial carcinoma (any histology) with cervical stromal invasion. (occult or gross involvement), with or without high-intermediate risk factors. 3. Patients with serous or clear cell histology (with or without other high-intermediate risk factors) are eligible provided the disease is uterine-confined (with or without cervical stromal invasion or endocervical glandular involvement). 5. Patients must have GOG performance status 0, 1, or 2. 6. Patients must have adequate bone marrow, renal, hepatic and neurologic function per protocol. 7. Patients who have met the pre-entry requirements specified in protocol; testing values/results must meet eligibility criteria specified in protocol. 8. Patients must have signed an approved informed consent and authorization permitting release of personal health information.
Exclusion criteria
1. Patients with recurrent disease. 2. Patients with GOG performance status of 3 or 4. 3. Greater than 12 weeks elapsed from surgery to enrollment. 4. Patients have prior pelvic or abdominal radiation therapy. 5. Known hypersensitivity to any component of study treatment that resulted in drug discontinuation. 6. Significant intercurrent illness including, but not limited to, unstable angina pectoris, and cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements 7. Active pregnancy or lactation. 8. Prior malignancy requiring treatment within the last 3 years.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients Completing the Protocol | 4 months | Defined as completion of vaginal cuff brachytherapy followed by 3 cycles of dose dense paclitaxel and carboplatin chemotherapy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of Adverse Events Related to Acute Toxicity During Treatment | 4 months | Frequency and severity of adverse events as assessed by the CTCAE v4 |
| Sites of Failure | up to 2 years | Proportion of participants who experienced failure in regional or distant sites |
| Recurrence-free Survival | up to 2 years | time from study entry to the first tumor recurrence |
| Contributing Cause of Death | up to 2 years | The contributing cause of death for patients with high risk endometrial cancer |
| Overall Survival | up to 2 years | time from study entry to death |
Countries
United States
Participant flow
Recruitment details
Participants were recruited at a single institution from October 2017 to July 2019. The first patient was enrolled on October 2, 2017 and the last patient was enrolled on July 23, 2019
Pre-assignment details
Of 39 enrolled participants, 32 met inclusion criteria and evaluable then assign to the single arm treatment.
Participants by arm
| Arm | Count |
|---|---|
| Vaginal Cuff Brachytherapy + Chemotherapy Vaginal cuff brachytherapy followed by Carboplatin (AUC 6) on day 1and Paclitaxel 80 mg/m2 IV over 1 hour days 1, 8, and 15 X 3 total cycles
Vaginal Cuff Brachytherapy: Within 12 weeks of surgery. Either LDR or HDR brachytherapy will be permitted
Carboplatin: Carboplatin IV on day 1 of a 21 day cycle for 3 cycles
Paclitaxel: Paclitaxel IV on days 1,8 and 15 of a 21 day cycle for 3 cycles | 32 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Vaginal Cuff Brachytherapy + Chemotherapy |
|---|---|
| Age, Continuous | 64.5 years |
| Body Mass Index | 35.1 kg/m^2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 30 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 28 Participants |
| Region of Enrollment United States | 32 participants |
| Sex: Female, Male Female | 32 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 32 |
| other Total, other adverse events | 10 / 32 |
| serious Total, serious adverse events | 0 / 32 |
Outcome results
Primary
Number of Patients Completing the Protocol
Defined as completion of vaginal cuff brachytherapy followed by 3 cycles of dose dense paclitaxel and carboplatin chemotherapy
Time frame: 4 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vaginal Cuff Brachytherapy + Chemotherapy | Number of Patients Completing the Protocol | 27 Participants |
Secondary
Contributing Cause of Death
The contributing cause of death for patients with high risk endometrial cancer
Time frame: up to 2 years
Population: Number of patients who died following protocol treatment
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Vaginal Cuff Brachytherapy + Chemotherapy | Contributing Cause of Death | Unknown cause of death | 1 Participants |
| Vaginal Cuff Brachytherapy + Chemotherapy | Contributing Cause of Death | Alive | 31 Participants |
Secondary
Frequency of Adverse Events Related to Acute Toxicity During Treatment
Frequency and severity of adverse events as assessed by the CTCAE v4
Time frame: 4 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vaginal Cuff Brachytherapy + Chemotherapy | Frequency of Adverse Events Related to Acute Toxicity During Treatment | 9 Participants |
Secondary
Overall Survival
time from study entry to death
Time frame: up to 2 years
Population: Patients who received protocol treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Vaginal Cuff Brachytherapy + Chemotherapy | Overall Survival | NA months |
Secondary
Recurrence-free Survival
time from study entry to the first tumor recurrence
Time frame: up to 2 years
Population: patients who received protocol therapy
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Vaginal Cuff Brachytherapy + Chemotherapy | Recurrence-free Survival | NA months |
Secondary
Sites of Failure
Proportion of participants who experienced failure in regional or distant sites
Time frame: up to 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vaginal Cuff Brachytherapy + Chemotherapy | Sites of Failure | 0 Participants |