Ignite Creation Date:
2024-05-05 @ 12:05 PM
Last Modification Date:
2024-10-26 @ 9:19 AM
Study NCT ID:
NCT00231868
Status:
COMPLETED
Last Update Posted:
2020-08-12
First Post:
2005-10-03
Brief Title:
A Study of Radiation Therapy and Paclitaxel and Carboplatin in Patients With Uterine Papillary Serous Carcinoma
Sponsor:
Montefiore Medical Center
Organization:
Montefiore Medical Center
Study Overview
Official Title:
A Pilot Phase II Trial of Radiation Therapy Sandwiched Between Paclitaxel and Carboplatin in Patients With Uterine Papillary Serous Carcinoma
Status:
COMPLETED
Status Verified Date:
2020-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Combination chemoradiotherapy trials in advancedrecurrent endometrial cancer are ongoing The optimal radiation modality chemotherapeutic agents and sequence of these regimens for the treatment of UPSC are yet to be established A retrospective review of 16 patients treated at our institution with the sequential use of radiation sandwiched between paclitaxelplatinum chemotherapy found only one patient to have recurred at 16 months with a median follow-up of 15 months range 6-33 months The regimen was well tolerated Eight of the sixteen patients 50 developed grade 3 neutropenia following cycle 4 of chemotherapy two of which required a 1 week treatment delay There were no cases of grade 3 or 4 thrombocytopenia noted There was no febrile neutropenia and no hospital admissions for toxicity There were no observed grade 3 or 4 non-hematologic toxicities With the median follow up of 15 months we have not observed late toxicities
Given these favorable preliminary findings supported by recently published data documenting efficacy of the sandwich multimodality technique in other difficult uterine malignancies malignant mixed mullerian tumors we propose to study this combination of chemotherapy and radiation prospectively Our aim is to better evaluate patterns of recurrence and possible benefits in progression-free and overall survival
Given these favorable preliminary findings supported by recently published data documenting efficacy of the sandwich multimodality technique in other difficult uterine malignancies malignant mixed mullerian tumors we propose to study this combination of chemotherapy and radiation prospectively Our aim is to better evaluate patterns of recurrence and possible benefits in progression-free and overall survival
Detailed Description:
Uterine papillary serous carcinoma UPSC is an uncommon but aggressive variant of endometrial carcinoma that has a high recurrence rate and poor response to therapy It has a propensity to metastasize throughout the abdomen similar to serous carcinoma of the ovary In fact many patients with disease apparently confined to the uterus have microscopic intra-abdominal spread at the time of diagnosis Recurrences are common both in the pelvis as well as in the upper abdomen
After staging and debulking of gross disease adjuvant radiation therapy is recommended to treat patients with endometrial carcinoma at high risk for recurrent disease High-risk features include histologic cell type grade depth of myometrial invasion cervical extension lymph-vascular invasion adnexal involvement intraperitoneal spread positive peritoneal cytology and positive lymph nodes Pelvic radiation can limit local recurrences to less than 65 However approximately 25-30 of patients with high-risk features who receive radiation recur with distant metastases Even patients treated with whole abdominal irradiation are at risk for extra-abdominal recurrences with progression-free intervals of 7 to 8 months
Adjuvant chemotherapeutic regimens have been studied in high-risk endometrial cancers but none have demonstrated a survival advantage Doxorubicin in combination with platinum has a reported 42 response rate but a high toxicity profile Paclitaxel has an overall response rate of 36 in patients with advanced and recurrent endometrial cancer Platinum-based chemotherapies have a 28-42 response rate
Retrospective studies in patients with UPSC have demonstrated response rates of up to 35 in patients with multiagent chemotherapy In one study a median progression-free interval of 30 months was observed in patients treated with paclitaxel and platinum in the adjuvant and recurrent settings Based on these findings and the similarities and clinical success of paclitaxelplatinum therapy in patients with ovarian serous carcinoma this combination warrants further investigation in a prospective manner in patients with UPSC
Combination chemoradiotherapy trials in advancedrecurrent endometrial cancer are ongoing The optimal radiation modality chemotherapeutic agents and sequence of these regimens for the treatment of UPSC are yet to be established A retrospective review of 16 patients treated at our institution with the sequential use of radiation sandwiched between paclitaxelplatinum chemotherapy found only one patient to have recurred at 16 months with a median follow-up of 15 months range 6-33 months The regimen was well tolerated Eight of the sixteen patients 50 developed grade 3 neutropenia following cycle 4 of chemotherapy two of which required a 1 week treatment delay There were no cases of grade 3 or 4 thrombocytopenia noted There was no febrile neutropenia and no hospital admissions for toxicity There were no observed grade 3 or 4 non-hematologic toxicities With the median follow up of 15 months we have not observed late toxicities
Given these favorable preliminary findings supported by recently published data documenting efficacy of the sandwich multimodality technique in other difficult uterine malignancies malignant mixed mullerian tumors we propose to study this combination of chemotherapy and radiation prospectively Our aim is to better evaluate patterns of recurrence and possible benefits in progression-free and overall survival
Surrogate endpoint biomarkers such as ERPR HER2Neu and p53 will be correlated with prognosis In addition fresh frozen tissue will be banked for future cDNA microarray analyses of UPSC tumors
After staging and debulking of gross disease adjuvant radiation therapy is recommended to treat patients with endometrial carcinoma at high risk for recurrent disease High-risk features include histologic cell type grade depth of myometrial invasion cervical extension lymph-vascular invasion adnexal involvement intraperitoneal spread positive peritoneal cytology and positive lymph nodes Pelvic radiation can limit local recurrences to less than 65 However approximately 25-30 of patients with high-risk features who receive radiation recur with distant metastases Even patients treated with whole abdominal irradiation are at risk for extra-abdominal recurrences with progression-free intervals of 7 to 8 months
Adjuvant chemotherapeutic regimens have been studied in high-risk endometrial cancers but none have demonstrated a survival advantage Doxorubicin in combination with platinum has a reported 42 response rate but a high toxicity profile Paclitaxel has an overall response rate of 36 in patients with advanced and recurrent endometrial cancer Platinum-based chemotherapies have a 28-42 response rate
Retrospective studies in patients with UPSC have demonstrated response rates of up to 35 in patients with multiagent chemotherapy In one study a median progression-free interval of 30 months was observed in patients treated with paclitaxel and platinum in the adjuvant and recurrent settings Based on these findings and the similarities and clinical success of paclitaxelplatinum therapy in patients with ovarian serous carcinoma this combination warrants further investigation in a prospective manner in patients with UPSC
Combination chemoradiotherapy trials in advancedrecurrent endometrial cancer are ongoing The optimal radiation modality chemotherapeutic agents and sequence of these regimens for the treatment of UPSC are yet to be established A retrospective review of 16 patients treated at our institution with the sequential use of radiation sandwiched between paclitaxelplatinum chemotherapy found only one patient to have recurred at 16 months with a median follow-up of 15 months range 6-33 months The regimen was well tolerated Eight of the sixteen patients 50 developed grade 3 neutropenia following cycle 4 of chemotherapy two of which required a 1 week treatment delay There were no cases of grade 3 or 4 thrombocytopenia noted There was no febrile neutropenia and no hospital admissions for toxicity There were no observed grade 3 or 4 non-hematologic toxicities With the median follow up of 15 months we have not observed late toxicities
Given these favorable preliminary findings supported by recently published data documenting efficacy of the sandwich multimodality technique in other difficult uterine malignancies malignant mixed mullerian tumors we propose to study this combination of chemotherapy and radiation prospectively Our aim is to better evaluate patterns of recurrence and possible benefits in progression-free and overall survival
Surrogate endpoint biomarkers such as ERPR HER2Neu and p53 will be correlated with prognosis In addition fresh frozen tissue will be banked for future cDNA microarray analyses of UPSC tumors
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None