Ignite Creation Date:
2024-05-06 @ 3:45 PM
Last Modification Date:
2024-10-26 @ 1:56 PM
Study NCT ID:
NCT04743999
Status:
TERMINATED
Last Update Posted:
2024-03-29
First Post:
2021-02-03
Brief Title:
Evaluation of Outcomes in Women Undergoing Multimodality Treatment for Advanced Stage Endometrial Carcinoma
Sponsor:
Henry Ford Health System
Organization:
Henry Ford Health System
Study Overview
Official Title:
Prospective Evaluation of Quality of Life and Treatment-related Side Effects of Women Undergoing Multimodality Treatment for Advanced Stage Endometrial Carcinoma
Status:
TERMINATED
Status Verified Date:
2024-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Low accrual
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Patients with FIGO stage III endometrial carcinoma often require multimodality adjuvant therapy to improve survival and recurrence rates however the optimal adjuvant therapy sequence is yet to be established
Several studies have tried to answer this question including RTOG 9708 PORTEC-3 and GOG 258 Collectively these studies show that concurrent chemotherapy and radiation chemoRT with cisplatin followed by additional chemotherapy CT and CT alone are acceptable regimens However both strategies show that distant recurrence remains a problem when CT is delayed after RT and local control is compromised without RT
We wish to prospectively assess outcomes of women with advanced endometrial carcinoma who receive concurrent chemoRT with a carboplatinpaclitaxel-based regimen
A total of 60 patients with FIGO stage III uterine carcinoma will be prospectively enrolled after undergoing surgical staging currently accruing CT will start approximately 4 weeks after surgery Patients will receive 6 cycles of carboplatin AUC 6 and paclitaxel 175 mgm2
RT will be given during CT cycles 1-3 External beam RT will be given via intensity-modulated RT in once-daily fractions of 18-20 Gy for a total dose of 44-45 Gy to the pelvis vaginal cuff pelvic LN and para-aortic lymph nodes If there is grossly visible nodal disease seen at the time of treatment planning a boost to 54 Gy will be given to those areas If the patient has cervical stromal invasion we will recommend that she receive a brachytherapy boost
Data will be collected on OS and PFS endpoints Data will also be collected on provider- and patient-reported treatment toxicity Patients will receive a series of questionnaires at baseline 3 6 12 and 24 months after surgery These are prospectively-validated questionnaires and include FACT-G FACT-En FACTGOG-NTX and FACT-C
For statistical analyses continuous and categorical variables will be analyzed Kaplan-Meier survival estimates will be calculated for local control and survival end points For each patient disease characteristics and adjuvant treatment will be placed in a simple logistic regression model for predicting survival endpoints A multivariate analysis will be performed for exploratory purposes Hazard ratios and 95 confidence intervals will be reported Tests will be considered significant at p 005
Several studies have tried to answer this question including RTOG 9708 PORTEC-3 and GOG 258 Collectively these studies show that concurrent chemotherapy and radiation chemoRT with cisplatin followed by additional chemotherapy CT and CT alone are acceptable regimens However both strategies show that distant recurrence remains a problem when CT is delayed after RT and local control is compromised without RT
We wish to prospectively assess outcomes of women with advanced endometrial carcinoma who receive concurrent chemoRT with a carboplatinpaclitaxel-based regimen
A total of 60 patients with FIGO stage III uterine carcinoma will be prospectively enrolled after undergoing surgical staging currently accruing CT will start approximately 4 weeks after surgery Patients will receive 6 cycles of carboplatin AUC 6 and paclitaxel 175 mgm2
RT will be given during CT cycles 1-3 External beam RT will be given via intensity-modulated RT in once-daily fractions of 18-20 Gy for a total dose of 44-45 Gy to the pelvis vaginal cuff pelvic LN and para-aortic lymph nodes If there is grossly visible nodal disease seen at the time of treatment planning a boost to 54 Gy will be given to those areas If the patient has cervical stromal invasion we will recommend that she receive a brachytherapy boost
Data will be collected on OS and PFS endpoints Data will also be collected on provider- and patient-reported treatment toxicity Patients will receive a series of questionnaires at baseline 3 6 12 and 24 months after surgery These are prospectively-validated questionnaires and include FACT-G FACT-En FACTGOG-NTX and FACT-C
For statistical analyses continuous and categorical variables will be analyzed Kaplan-Meier survival estimates will be calculated for local control and survival end points For each patient disease characteristics and adjuvant treatment will be placed in a simple logistic regression model for predicting survival endpoints A multivariate analysis will be performed for exploratory purposes Hazard ratios and 95 confidence intervals will be reported Tests will be considered significant at p 005
Detailed Description:
Purpose To prospectively determine patients quality of life QOL and treatment-related toxicity outcomes with adjuvant multimodality treatment chemotherapy and radiation treatment in women with advanced endometrial carcinoma after surgical staging
Specific Aims
1 To prospectively determine QOL after adjuvant treatment using the prospectively-validated FACT questionnaires at baseline 3 6 12 and 24 months after surgical staging
2 To prospectively determine the rate of any grade 2 or higher treatment-related side effects mainly bone marrow suppression lymphedema diarrhea and others Additionally we will collect information about the rate of completion of planned adjuvant treatment number of chemotherapy cycles dose reduction or chemotherapy delay radiation treatment interruption etc
3 To prospectively collect survival outcome endpoints after adjuvant treatment recurrence-free disease-specific and overall survival
Introduction and Rationale Endometrial cancer is the most common gynecologic malignancy in the United States and ranks second in gynecologic cancer mortality following only ovarian cancer More than 84 of patients present with International Federation of Gynecology and Obstetrics FIGO stage I-II disease By definition patients with advanced-stage uterine carcinoma FIGO stages III-IV are those with extrauterine disease and are at significant risk of dying from uterine cancer They constitute a very heterogeneous group of patients with varying risk factors yielding highly variable clinical outcomes Within the same FIGO stage patients with disease involving multiple extrauterine sites fare worse compared to patients with involvement of a single site 1
Postoperatively patients with advanced stage disease often require adjuvant therapys to reduce the chance of tumor recurrence with the potential to improve survival However the optimal adjuvant therapy is yet to be established with several options available for adjuvant treatment
Rationale for multimodality treatment with chemotherapy and radiation treatment CMT
Current treatment recommendations for advanced stage endometrial cancer consist of multiple approaches including chemotherapy alone radiotherapy RT alone or combined modality treatment CMT 2
GOG 122 study which was a phase III trial randomized patient with advanced endometrial carcinoma to adjuvant chemotherapy alone versus whole abdomen RT WART Outcomes of this study showed that the chemotherapy arm had an improved 5-year progression-free survival PFS and overall survival OS compared to RT alone However this trial showed that if chemotherapy is given alone that rate of local recurrence approaches 20 3
The safety of CMT with concurrent chemotherapy and RT chemoRT was explored in RTOG 9708 which was a phase II trial that evaluated outcomes in patients receiving concurrent chemoRT All patients received adjuvant pelvic RT 45 Gy concurrent with cisplatin followed by four additional cycles of cisplatin and paclitaxel The 4-year OS and PFS for patients with stage III disease were 77 and 72 respectively Rates of grade 1 toxicity were found in 16 of patients grade 2 in 41 grade 3 in 16 and grade 4 in 5 This study demonstrated that concurrent chemoRT is safe with excellent local control 4
More recent studies have sought to compare chemoRT to chemotherapy or radiation alone PORTEC-3 was a phase III randomized trial comparing adjuvant RT alone to concurrent chemoRT The RT dose was 486 Gy in 27 fractions and chemotherapy was concurrent cisplatin followed by an additional 4 cycles of carboplatin and paclitaxel For women with stage III disease the addition of chemotherapy to radiation treatment showed benefit in terms of improvement in FFS An analysis of toxicity outcomes found that 60 of patients in the chemoRT arm experienced a grade 3 or greater adverse event compared to 12 in the RT alone arm p00001 5
GOG 258 study was recently published and was similar to PORTEC-3 except that it compared concurrent chemoRT to adjuvant chemotherapy alone Patients were randomized to receive concurrent chemoRT 45 Gy in 25 fractions concurrent with cisplatin followed by 4 cycles of carboplatin and paclitaxel or chemotherapy alone The results of this study showed that chemoRT was associated with a lower 5-year incidence of vaginal and regional lymphatic recurrence However distant recurrence rates were higher in the chemoRT arm compared to chemotherapy alone 6
The above studies helped to establish concurrent chemoRT with cisplatin followed by adjuvant carboplatinpaclitaxel as a valid adjuvant treatment approach for women with advanced endometrial carcinoma
A retrospective review from Washington University included 51 women with stage III-IV endometrial carcinoma who received CMT with carboplatinpaclitaxel-based regimen concurrent with RT and assessed survival and toxicity outcomes The chemotherapy regimen given was carboplatinpaclitaxel for 4-6 cycles and RT was 48-512 Gy Patients also received a vaginal brachytherapy boost They found that 48 patients 94 completed chemotherapy and 16 patients 30 required chemotherapy dose-reduction Thirty-four patients experienced grade 3-4 toxicities most of which were hematologic Over 80 of patients required leukocyte growth factor injections There were seven late grade 3-4 toxicities 4 GI 2 GU and 1 ongoing neuropathy They found a median PFS of 428 months median OS of 449 months and 3-year OS of 80 7 This study suggests that concurrent chemoRT using a carbotaxol-based regimen has favorable outcomes a tolerable side effect profile and the potential to reduce overall treatment duration
Building off of the results of the above retrospective study as well as the aforementioned randomized trials we wish to prospectively assess outcomes of women with advanced endometrial carcinoma who receive the same concurrent chemoRT with a carboplatinpaclitaxel-based regimen
Specific Aims
1 To prospectively determine QOL after adjuvant treatment using the prospectively-validated FACT questionnaires at baseline 3 6 12 and 24 months after surgical staging
2 To prospectively determine the rate of any grade 2 or higher treatment-related side effects mainly bone marrow suppression lymphedema diarrhea and others Additionally we will collect information about the rate of completion of planned adjuvant treatment number of chemotherapy cycles dose reduction or chemotherapy delay radiation treatment interruption etc
3 To prospectively collect survival outcome endpoints after adjuvant treatment recurrence-free disease-specific and overall survival
Introduction and Rationale Endometrial cancer is the most common gynecologic malignancy in the United States and ranks second in gynecologic cancer mortality following only ovarian cancer More than 84 of patients present with International Federation of Gynecology and Obstetrics FIGO stage I-II disease By definition patients with advanced-stage uterine carcinoma FIGO stages III-IV are those with extrauterine disease and are at significant risk of dying from uterine cancer They constitute a very heterogeneous group of patients with varying risk factors yielding highly variable clinical outcomes Within the same FIGO stage patients with disease involving multiple extrauterine sites fare worse compared to patients with involvement of a single site 1
Postoperatively patients with advanced stage disease often require adjuvant therapys to reduce the chance of tumor recurrence with the potential to improve survival However the optimal adjuvant therapy is yet to be established with several options available for adjuvant treatment
Rationale for multimodality treatment with chemotherapy and radiation treatment CMT
Current treatment recommendations for advanced stage endometrial cancer consist of multiple approaches including chemotherapy alone radiotherapy RT alone or combined modality treatment CMT 2
GOG 122 study which was a phase III trial randomized patient with advanced endometrial carcinoma to adjuvant chemotherapy alone versus whole abdomen RT WART Outcomes of this study showed that the chemotherapy arm had an improved 5-year progression-free survival PFS and overall survival OS compared to RT alone However this trial showed that if chemotherapy is given alone that rate of local recurrence approaches 20 3
The safety of CMT with concurrent chemotherapy and RT chemoRT was explored in RTOG 9708 which was a phase II trial that evaluated outcomes in patients receiving concurrent chemoRT All patients received adjuvant pelvic RT 45 Gy concurrent with cisplatin followed by four additional cycles of cisplatin and paclitaxel The 4-year OS and PFS for patients with stage III disease were 77 and 72 respectively Rates of grade 1 toxicity were found in 16 of patients grade 2 in 41 grade 3 in 16 and grade 4 in 5 This study demonstrated that concurrent chemoRT is safe with excellent local control 4
More recent studies have sought to compare chemoRT to chemotherapy or radiation alone PORTEC-3 was a phase III randomized trial comparing adjuvant RT alone to concurrent chemoRT The RT dose was 486 Gy in 27 fractions and chemotherapy was concurrent cisplatin followed by an additional 4 cycles of carboplatin and paclitaxel For women with stage III disease the addition of chemotherapy to radiation treatment showed benefit in terms of improvement in FFS An analysis of toxicity outcomes found that 60 of patients in the chemoRT arm experienced a grade 3 or greater adverse event compared to 12 in the RT alone arm p00001 5
GOG 258 study was recently published and was similar to PORTEC-3 except that it compared concurrent chemoRT to adjuvant chemotherapy alone Patients were randomized to receive concurrent chemoRT 45 Gy in 25 fractions concurrent with cisplatin followed by 4 cycles of carboplatin and paclitaxel or chemotherapy alone The results of this study showed that chemoRT was associated with a lower 5-year incidence of vaginal and regional lymphatic recurrence However distant recurrence rates were higher in the chemoRT arm compared to chemotherapy alone 6
The above studies helped to establish concurrent chemoRT with cisplatin followed by adjuvant carboplatinpaclitaxel as a valid adjuvant treatment approach for women with advanced endometrial carcinoma
A retrospective review from Washington University included 51 women with stage III-IV endometrial carcinoma who received CMT with carboplatinpaclitaxel-based regimen concurrent with RT and assessed survival and toxicity outcomes The chemotherapy regimen given was carboplatinpaclitaxel for 4-6 cycles and RT was 48-512 Gy Patients also received a vaginal brachytherapy boost They found that 48 patients 94 completed chemotherapy and 16 patients 30 required chemotherapy dose-reduction Thirty-four patients experienced grade 3-4 toxicities most of which were hematologic Over 80 of patients required leukocyte growth factor injections There were seven late grade 3-4 toxicities 4 GI 2 GU and 1 ongoing neuropathy They found a median PFS of 428 months median OS of 449 months and 3-year OS of 80 7 This study suggests that concurrent chemoRT using a carbotaxol-based regimen has favorable outcomes a tolerable side effect profile and the potential to reduce overall treatment duration
Building off of the results of the above retrospective study as well as the aforementioned randomized trials we wish to prospectively assess outcomes of women with advanced endometrial carcinoma who receive the same concurrent chemoRT with a carboplatinpaclitaxel-based regimen
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None