Ignite Creation Date:
2024-05-06 @ 2:49 AM
Last Modification Date:
2024-10-26 @ 11:24 AM
Study NCT ID:
NCT02137356
Status:
UNKNOWN
Last Update Posted:
2015-09-03
First Post:
2014-05-01
Brief Title:
Selinexor Combined With Standard Chemoradiation as Neoadjuvant Treatment in Locally Advanced Rectal Cancer
Sponsor:
Sheba Medical Center
Organization:
Sheba Medical Center
Study Overview
Official Title:
An Investigator Sponsored Phase I Trial of Selinexor Combined With Standard Capecitabine Based Chemoradiation as a Neoadjuvant Treatment in Locally Advanced Rectal Cancer
Status:
UNKNOWN
Status Verified Date:
2015-09
Last Known Status:
RECRUITING
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:
Locally advanced rectal cancer T3 T4 or lymph node positive tumors are conventionally treated with 5FU capecitabine based chemoradiation prior to surgical resection This treatment is associated with only a 15-20 pathological complete response Selinexor KPT-330 is a Selective Inhibitor of Nuclear Export SINE XPO1 antagonist that has demonstrated radiosensitization with in vivo models and has suggested single agent activity against colorectal cancers in a Phase I trial Here we perform a Phase IIb trial of standard chemoradiation combined with Selinexor
We hypothesize that tumors treated with this new combination will demonstrate an increased response rate compared to those treated with capecitabine-radiation alone
We hypothesize that tumors treated with this new combination will demonstrate an increased response rate compared to those treated with capecitabine-radiation alone
Detailed Description:
The American Cancer Society estimated that in 2012 there were 40290 new cases of rectal cancer in the United States In the 1980s the standard of care was surgical resection alone unfortunately this was associated with high rates of local recurrence 30 in node positive or T3-4 disease Randomized studies demonstrated the efficacy of adding post-operative and subsequently pre-operative chemo-radiation Preoperative radiation either on its own or with concomitant chemotherapy decreases local recurrence increases disease-free and overall survival and improves rates of sphincter preservation
The current standard of care in the United States and Israel for patients with node positive or T3 of T4 disease is preoperative chemo-radiation The radiation is delivered to a dose of 45-55 Gy delivered over 5-6 weeks The chemotherapy traditionally employed was infusional 5- fluorouracil 5FU In recent years this has been replaced by an oral 5FU derivative Capecitabine15 Some European centers favor an intense short-course preoperative radiation regimen of 25Gy over 5 days This regimen is rarely used in Israel or the United States for logistical reasons surgery needs to be rigidly scheduled immediately after completion of radiation and concerns about long-term side effects
Pathological complete response is when at the time of operation no cancerous tissue is found in the operative specimen Pathological complete response is indicative of both the sensitivity of the tumor and the effectiveness of the preoperative chemotherapeutic regimen Pathological complete response is associated with an excellent prognosis in terms of local recurrence distal recurrence and overall survival Standard preoperative chemoradiation is associated with a pathological complete response of 15-20 For patients with locally advanced disease receiving standard chemoradiation the 5 year local recurrence rate is expected to be 6 and 5 year survival 68
This open label study is therefore proposed to examine the combination of chemoradiation with Selinexor a SINE XPO1 antagonist that is being evaluated in Phase 1 studies in solid and hematological malignancies and that has shown single agent activity in heavily pretreated patients with CRC The long-term goal of the project Is to establish a new treatment for patients with rectal cancer that will improve their cure rate and lengthen their overall survival
The current standard of care in the United States and Israel for patients with node positive or T3 of T4 disease is preoperative chemo-radiation The radiation is delivered to a dose of 45-55 Gy delivered over 5-6 weeks The chemotherapy traditionally employed was infusional 5- fluorouracil 5FU In recent years this has been replaced by an oral 5FU derivative Capecitabine15 Some European centers favor an intense short-course preoperative radiation regimen of 25Gy over 5 days This regimen is rarely used in Israel or the United States for logistical reasons surgery needs to be rigidly scheduled immediately after completion of radiation and concerns about long-term side effects
Pathological complete response is when at the time of operation no cancerous tissue is found in the operative specimen Pathological complete response is indicative of both the sensitivity of the tumor and the effectiveness of the preoperative chemotherapeutic regimen Pathological complete response is associated with an excellent prognosis in terms of local recurrence distal recurrence and overall survival Standard preoperative chemoradiation is associated with a pathological complete response of 15-20 For patients with locally advanced disease receiving standard chemoradiation the 5 year local recurrence rate is expected to be 6 and 5 year survival 68
This open label study is therefore proposed to examine the combination of chemoradiation with Selinexor a SINE XPO1 antagonist that is being evaluated in Phase 1 studies in solid and hematological malignancies and that has shown single agent activity in heavily pretreated patients with CRC The long-term goal of the project Is to establish a new treatment for patients with rectal cancer that will improve their cure rate and lengthen their overall survival
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