Vaginal Cuff Brachytherapy Followed by Chemotherapy in Endometrial Cancer

• Sponsor: University of Oklahoma (Other)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT03189446
• Collaborator: (none)
• Enrollment: 39
• Location: 1
• Arm: 1
• Anticipated Duration (Months): 62.4
• Patients Per Site Per Month: 0.6

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Endometrial Cancer; Papillary Serous; Clear Cell Endometrial Cancer	Radiation: Vaginal Cuff Brachytherapy; Drug: Carboplatin; Drug: Paclitaxel	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 39 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Trial of Vaginal Cuff Brachytherapy Followed by Adjuvant Chemotherapy With Carboplatin and Dose Dense Paclitaxel in Patients With High-Risk Endometrial Cancer
• Actual Study Start Date: Oct 2, 2017
• Actual Primary Completion Date: Dec 13, 2019
• Anticipated Study Completion Date: Dec 13, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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	Radiation: Vaginal Cuff Brachytherapy; Within 12 weeks of surgery. Either LDR or HDR brachytherapy will be permitted; Drug: Carboplatin; Carboplatin IV on day 1 of a 21 day cycle for 3 cycles; Drug: Paclitaxel; Paclitaxel IV on days 1,8 and 15 of a 21 day cycle for 3 cycles

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. Frequency of Adverse Events Related to Acute Toxicity During Treatment [4 months]

   Frequency and severity of adverse events as assessed by the CTCAE v4

2. Sites of Failure [up to 2 years]

   Proportion of participants who recur in regional versus distant recurrence

3. Recurrence-free Survival [up to 2 years]

   time from study entry to the first tumor recurrence

4. Contributing Cause of Death [up to 2 years]

   The contributing cause of death for patients with high risk endometrial cancer

5. Overall Survival [up to 2 years]

   time from study entry to death

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 99 Years
• Sexes Eligible for Study: Female
• Accepts 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).

4. Patients must have GOG performance status 0, 1, or 2.

5. Patients must have adequate bone marrow, renal, hepatic and neurologic function per protocol.

6. Patients who have met the pre-entry requirements specified in protocol; testing values/results must meet eligibility criteria specified in protocol.

7. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stephenson Cancer Center	Oklahoma City	Oklahoma	United States	73104

Sponsors and Collaborators

• University of Oklahoma

Investigators

• Principal Investigator: Kathleen Moore, MD, Stephenson Cancer Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Nov 4, 2020
• Informed Consent Form - Jan 27, 2017

More Information

Publications

None provided.

• Responsible Party: University of Oklahoma
• ClinicalTrials.gov Identifier: NCT03189446
• Other Study ID Numbers: 7964
• First Posted: Jun 16, 2017
• Last Update Posted: Aug 17, 2021
• Last Verified: Aug 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by University of Oklahoma: Endometrial Cancer; Gynecologic Cancer; radiation therapy
• Additional relevant MeSH terms: Endometrial Neoplasms; Paclitaxel; Carboplatin

Study Results

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 Detail	Of 39 enrolled participants, 32 met inclusion criteria and evaluable then assign to the single arm treatment.

Arm/Group Title	Vaginal Cuff Brachytherapy + Chemotherapy
Arm/Group Description	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
Period Title: Overall Study
STARTED	32
COMPLETED	27
NOT COMPLETED	5

Baseline Characteristics

Arm/Group Title	Vaginal Cuff Brachytherapy + Chemotherapy
Arm/Group Description	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
Overall Participants	32
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	64.5
Sex: Female, Male (Count of Participants)
Female	32 100%
Male	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 6.3%
Not Hispanic or Latino	30 93.8%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 3.1%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 3.1%
White	28 87.5%
More than one race	0 0%
Unknown or Not Reported	2 6.3%
Region of Enrollment (participants) [Number]
United States	32 100%
Body Mass Index (kg/m^2) [Median (Full Range) ]
Median (Full Range) [kg/m^2]	35.1

Outcome Measures

1. Primary Outcome

Title	Number of Patients Completing the Protocol
Description	Defined as completion of vaginal cuff brachytherapy followed by 3 cycles of dose dense paclitaxel and carboplatin chemotherapy
Time Frame	4 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vaginal Cuff Brachytherapy + Chemotherapy
Arm/Group Description	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
Measure Participants	32
Count of Participants [Participants]	27 84.4%

2. Secondary Outcome

Title	Frequency of Adverse Events Related to Acute Toxicity During Treatment
Description	Frequency and severity of adverse events as assessed by the CTCAE v4
Time Frame	4 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vaginal Cuff Brachytherapy + Chemotherapy
Arm/Group Description	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
Measure Participants	32
Count of Participants [Participants]	9 28.1%

3. Secondary Outcome

Title	Sites of Failure
Description	Proportion of participants who recur in regional versus distant recurrence
Time Frame	up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Recurrence-free Survival
Description	time from study entry to the first tumor recurrence
Time Frame	up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Contributing Cause of Death
Description	The contributing cause of death for patients with high risk endometrial cancer
Time Frame	up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Secondary Outcome

Title	Overall Survival
Description	time from study entry to death
Time Frame	up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	4 months
Arm/Group Title	Vaginal Cuff Brachytherapy + Chemotherapy
Arm/Group Description	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
All Cause Mortality
	Vaginal Cuff Brachytherapy + Chemotherapy
	Affected / at Risk (%)	# Events
Total	0/32 (0%)
Serious Adverse Events
	Vaginal Cuff Brachytherapy + Chemotherapy
	Affected / at Risk (%)	# Events
Total	0/32 (0%)
Other (Not Including Serious) Adverse Events
	Vaginal Cuff Brachytherapy + Chemotherapy
	Affected / at Risk (%)	# Events
Total	10/32 (31.3%)
Blood and lymphatic system disorders
Anemia	2/32 (6.3%)
Gastrointestinal disorders
Diarrhea	2/32 (6.3%)
General disorders
Fatigue	2/32 (6.3%)
Immune system disorders
Taxol Reaction	3/32 (9.4%)
Nervous system disorders
Peripheral Neuropathy	2/32 (6.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.