Ignite Creation Date:
2025-12-24 @ 1:48 PM
Ignite Modification Date:
2025-12-24 @ 1:48 PM
Study NCT ID:
NCT04418895
Status:
WITHDRAWN
Last Update Posted:
2021-11-10
First Post:
2020-06-02
Is Possible Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Neoadjuvant Therapy for Localized Rectal Adenocarcinoma
Sponsor:
UNC Lineberger Comprehensive Cancer Center
Organization:
Study Overview
Official Title:
Biomarkers and Clinical Outcomes in Localized Rectal Adenocarcinoma Treated With Neoadjuvant Therapy
Status:
WITHDRAWN
Status Verified Date:
2021-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
lack of resources
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study is a prospective, single-arm, single-center study of investigator's choice of total neoadjuvant therapy (TNT) or neoadjuvant chemoradiation in locally advanced rectal cancer. The standard of care for rectal adenocarcinomas that are triiodothyronine-thyroxine (T3-T4) or node positive has generally been comprised of neoadjuvant chemoradiation, followed by surgical resection and then adjuvant chemotherapy. More recently, TNT, comprised of neoadjuvant chemotherapy and chemoradiation followed by surgical resection, has been increasingly used as a standard therapy approach. While the use of TNT is increasingly common, prospective study of outcomes following TNT has been limited. Moreover, there are not any biomarkers known at this time that impact clinical decision-making or personalization of therapy in the treatment of rectal cancer. In this study, we will collect pre-treatment rectal adenocarcinoma specimens and determine clinical outcome, including pathologic complete response rate, post-treatment pathologic downstaging rate, recurrence-free survival (RFS), overall survival (OS) and neoadjuvant rectal score, among patients who are treated with standard neoadjuvant chemoradiation or TNT, with an aim to investigate how baseline biomarkers and changes in biomarkers with standard therapies may be associated with, and modulate, clinical outcomes.
Detailed Description:
At enrollment, subjects should be planned to receive either neoadjuvant chemoradiation or total neoadjuvant therapy, with the choice of regimen at the discretion of treating investigators. Subjects will have been staged as deemed consistent with standard of care, including either a pelvic Magnetic resonance imaging (MRI) and/or an endorectal ultrasound, and deemed to have either T3-T4 primary tumor or node-positive tumor.
Neoadjuvant Chemoradiation Subjects will undergo endoscopic tumor biopsy within 6 weeks of the start of standard of care chemoradiation. Subjects will also have a baseline peripheral blood sample collected.
Subjects will receive neoadjuvant chemoradiation per standard of care. This is typically comprised of radiotherapy with concurrent capecitabine 825 mg/m2 by mouth (po) two times daily (bid) (typically rounded to the nearest 500 mg dose) or infusional 5-fluorouracil (5FU). However, dosing and administration are at the discretion of the treating medical and radiation oncologist.
An acceptable alternative approach is short-course radiation therapy per standard of care, which is typically comprised of radiotherapy, with surgery within 1 week of completion of therapy or delayed for 6-8 weeks. Selection of the optimal radiation therapy approach is at the discretion of the treating medical oncologist, radiation oncologist, and surgical oncologist. However, generally, short-course radiation therapy is not recommended for low-lying tumors less than 5 centimeters (cm) from the anal verge.
Occasionally patients with inadequate response after neoadjuvant chemoradiation may be recommended to proceed with subsequent consolidative chemotherapy with 5-Fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or capecitabine and oxaliplatin (CAPOX) for 16-18 weeks before surgical resection. This treatment is at the discretion of the treating medical oncologist, radiation oncologist, and surgical oncologist. These subjects will be allowed to remain on study.
Surgery will occur approximately 4-8 weeks after chemoradiation or consolidative chemotherapy, depending on clinical factors (i.e. resectability, presence or absence of metastatic disease), although it may occur as soon as 1 week after completing short-course radiation therapy. The timing of surgical resection after completion of neoadjuvant therapy is at the discretion of the treating surgical oncologist. At the time of surgery, tumor samples and peripheral blood samples for correlative studies will be collected.
Subjects who do not receive preoperative mFOLFOX6 or CAPOX typically receive postoperative adjuvant chemotherapy with a fluoropyrimidine +/- oxaliplatin for an additional 16-18 weeks of therapy, if permitted based on recovery after surgical resection and post-surgical performance status. This treatment is at the discretion of the treating medical oncologist. Subjects will remain on study regardless of postoperative therapy administration or duration.
Total Neoadjuvant Therapy Subjects will undergo endoscopic tumor biopsy within 6 weeks of the start of standard of care treatment with chemotherapy. Subjects will also have a baseline peripheral blood sample collected.
Subjects who are intended to receive total neoadjuvant therapy will typically receive chemotherapy with mFOLFOX6 or CAPOX for 16-18 weeks, followed by chemoradiation. Dosing and administration are at the discretion of the primary medical and radiation oncologist. Alternative subsequent approaches such as short-course radiotherapy are also acceptable at the discretion of the treating medical and radiation oncologist.
Surgery will occur approximately 4-8 weeks after chemoradiation depending on clinical factors (i.e. resectability, presence or absence of metastatic disease), although it may occur as soon as 1 week after completing short-course radiation therapy. The timing of surgical resection after completion of neoadjuvant therapy is at the discretion of the treating surgical oncologist. At the time of surgery, tumor samples and peripheral blood samples for correlative studies will be collected.
Duration of Therapy
The duration of therapy should be defined per the subject's standard of care. Reasons to discontinue treatment may include:
* Disease progression
* Inter-current illness that prevents further administration of treatment
* Unacceptable adverse event(s)
* Pregnancy
* Subject decides to withdraw from study treatment, or
* General or specific changes in the subject's condition render the subject unacceptable for further treatment in the judgment of the investigator.
* Subject has completed the treatment regimen
* Subject is lost to follow up
Duration of Follow Up After surgery, subjects will be followed with routine surveillance at the discretion of treating investigators. Subjects will be followed for survival and disease status for at least 3 years after surgery or until death, whichever occurs first.
Neoadjuvant Chemoradiation Subjects will undergo endoscopic tumor biopsy within 6 weeks of the start of standard of care chemoradiation. Subjects will also have a baseline peripheral blood sample collected.
Subjects will receive neoadjuvant chemoradiation per standard of care. This is typically comprised of radiotherapy with concurrent capecitabine 825 mg/m2 by mouth (po) two times daily (bid) (typically rounded to the nearest 500 mg dose) or infusional 5-fluorouracil (5FU). However, dosing and administration are at the discretion of the treating medical and radiation oncologist.
An acceptable alternative approach is short-course radiation therapy per standard of care, which is typically comprised of radiotherapy, with surgery within 1 week of completion of therapy or delayed for 6-8 weeks. Selection of the optimal radiation therapy approach is at the discretion of the treating medical oncologist, radiation oncologist, and surgical oncologist. However, generally, short-course radiation therapy is not recommended for low-lying tumors less than 5 centimeters (cm) from the anal verge.
Occasionally patients with inadequate response after neoadjuvant chemoradiation may be recommended to proceed with subsequent consolidative chemotherapy with 5-Fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or capecitabine and oxaliplatin (CAPOX) for 16-18 weeks before surgical resection. This treatment is at the discretion of the treating medical oncologist, radiation oncologist, and surgical oncologist. These subjects will be allowed to remain on study.
Surgery will occur approximately 4-8 weeks after chemoradiation or consolidative chemotherapy, depending on clinical factors (i.e. resectability, presence or absence of metastatic disease), although it may occur as soon as 1 week after completing short-course radiation therapy. The timing of surgical resection after completion of neoadjuvant therapy is at the discretion of the treating surgical oncologist. At the time of surgery, tumor samples and peripheral blood samples for correlative studies will be collected.
Subjects who do not receive preoperative mFOLFOX6 or CAPOX typically receive postoperative adjuvant chemotherapy with a fluoropyrimidine +/- oxaliplatin for an additional 16-18 weeks of therapy, if permitted based on recovery after surgical resection and post-surgical performance status. This treatment is at the discretion of the treating medical oncologist. Subjects will remain on study regardless of postoperative therapy administration or duration.
Total Neoadjuvant Therapy Subjects will undergo endoscopic tumor biopsy within 6 weeks of the start of standard of care treatment with chemotherapy. Subjects will also have a baseline peripheral blood sample collected.
Subjects who are intended to receive total neoadjuvant therapy will typically receive chemotherapy with mFOLFOX6 or CAPOX for 16-18 weeks, followed by chemoradiation. Dosing and administration are at the discretion of the primary medical and radiation oncologist. Alternative subsequent approaches such as short-course radiotherapy are also acceptable at the discretion of the treating medical and radiation oncologist.
Surgery will occur approximately 4-8 weeks after chemoradiation depending on clinical factors (i.e. resectability, presence or absence of metastatic disease), although it may occur as soon as 1 week after completing short-course radiation therapy. The timing of surgical resection after completion of neoadjuvant therapy is at the discretion of the treating surgical oncologist. At the time of surgery, tumor samples and peripheral blood samples for correlative studies will be collected.
Duration of Therapy
The duration of therapy should be defined per the subject's standard of care. Reasons to discontinue treatment may include:
* Disease progression
* Inter-current illness that prevents further administration of treatment
* Unacceptable adverse event(s)
* Pregnancy
* Subject decides to withdraw from study treatment, or
* General or specific changes in the subject's condition render the subject unacceptable for further treatment in the judgment of the investigator.
* Subject has completed the treatment regimen
* Subject is lost to follow up
Duration of Follow Up After surgery, subjects will be followed with routine surveillance at the discretion of treating investigators. Subjects will be followed for survival and disease status for at least 3 years after surgery or until death, whichever occurs first.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
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?: