Testing Chemotherapy versus Chemotherapy plus Radiotherapy Prior to Limited Surgery for Early Rectal Cancer
Testing Chemotherapy versus Chemotherapy plus Radiotherapy Prior to Limited Surgery for Early Rectal Cancer
This phase III trial compares the effect of the combination of fluorouracil, oxaliplatin, and leucovorin calcium (FOLFOX) or capecitabine and oxaliplatin (CAPOX) followed by limited surgery with transanal endoscopic surgery (TES) versus chemoradiation followed by TES for the treatment of early stage rectal cancer. The usual approach for patients who are not in a study is surgery to remove the rectum or treatment with chemotherapy and radiation therapy, followed by surgery. Fluorouracil stops cells from making deoxyribonucleic acid (DNA) and it may kill tumor cells. Leucovorin is in a class of medications called folic acid analogs. When used with fluorouracil, it enhances the effects of this chemotherapy drug. Oxaliplatin is in a class of medications called platinum-containing antineoplastic agents. It damages the cells DNA and may kill cancer cells. CAPOX is a combination of two drugs (capecitabine and oxaliplatin) and used as standard chemotherapy in treatment of rectal cancer. CAPOX works by damaging the DNA in tumor cells, and may cause the cells to stop growing and die. Radiation therapy uses high energy x-rays, particles, or radioactive seeds to kill tumor cells and shrink tumors. This study will help researchers find out if chemotherapy with FOLFOX or CAPOX prior to surgery works better, the same, or worse than the usual approach and improves the quality of life in patients with early rectal cancer.
Not Available
Phase III
Adults
Chemotherapy - cytotoxic,
Radiotherapy
5-FU (Fluorouracil),
5FU continuous infusion,
Capecitabine,
Leucovorin,
Oxaliplatin
Eng, Cathy
National
Vanderbilt University
04-08-2025
Eligibility
18 Years
BOTH
NO
Inclusion Criteria:
Histologically confirmed invasive, well-moderately differentiated rectal adenocarcinoma, mismatch repair proficient
MRI stage: * cT1 not eligible for transanal surgery alone as per National Comprehensive Cancer Network (NCCN) guidelines, (including but not limited to T1 tumours > 2 cm in size, positive margin, tumour depth SM3 invasion to the lower third of the submucosal level). or * cT2
cN0 stage based on pelvic MRI including absence of radiographic evidence of mesorectal nodal metastasis, tumour deposits or extramural venous invasion (EMVI)
M0 stage based on no evidence of metastatic disease by CT imaging of chest, abdomen and pelvis
Mid to low-lying tumour eligible for transanal excision in the opinion of the treating surgeon
Medically fit to undergo radical TME surgery as per treating surgeons decision
Participant is able (i.e. sufficiently fluent) and willing to complete the quality of life questionnaires in either English or French or Spanish. The baseline assessment must be completed within required timelines, prior to enrollment. Inability (lack of comprehension in English or French or Spanish, or other equivalent reason such as cognitive issues or lack of competency) to complete the questionnaires will not make the participant ineligible for the study. However, ability but unwillingness to complete the questionnaires will make the participant ineligible
Age of at least 18 years
No contraindications to protocol chemotherapy
Absolute neutrophil count (ANC) 1.5 x 10^9/L (must be done within 30 days prior to enrollment)
Platelet count 100 x 10^9/L (must be done within 30 days prior to enrollment)
Bilirubin 1.5 upper limit of normal (ULN), excluding Gilberts syndrome (must be done within 30 days prior to enrollment)
Estimated creatinine clearance of 50 ml/min (must be done within 30 days prior to enrollment)
The patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 2 (or Karnofsky 60%)
Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrollment in the trial to document their willingness to participate
Must be accessible for treatment and follow up. Investigators must assure themselves the patients enrolled on this trial will be available for complete documentation of the treatment, adverse events, follow-up and response assessments
Patients must agree to return to their primary care facility for any adverse events which may occur through the course of the trial
Women/men of childbearing potential must have agreed to use a highly effective contraceptive method during and for 6 months after completion of chemotherapy. A woman is considered to be of "childbearing potential" if she has had menses at any time in the preceding 12 consecutive months. In addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation, or vasectomy/vasectomized partner. However, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures
Women of childbearing potential will have a pregnancy test to determine eligibility as part of the pre-study evaluation; this may include an ultrasound to rule-out pregnancy if a false-positive is suspected
Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
Exclusion Criteria:
Pathologic high-risk factors on diagnostic biopsy: high histologic grade (poorly differentiated), mucinous or signet ring histology, lymphatic/vascular or perineural invasion
Patients with visible pelvic sidewall nodes on MRI
Patients with unequivocal determination of nodal disease that, in the opinion of the investigator, would prohibit protocol therapy administration
Previous pelvic radiation for any reason, including brachytherapy alone
Patients who have had primary lesion excised prior to enrollment
Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
Prior treatment for rectal cancer
Patients with known dihydropyrimidine dehydrogenase deficiency (DYPD)
Potential trial participants should have recovered from clinically significant adverse events of their most recent therapy/intervention prior to enrollment
Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
Any contra-indications to undergo MRI imaging
Presence of anterior lesions above or near peritoneal reflection rendering the patient ineligible for a transanal tumour excision
Histologically confirmed invasive, well-moderately differentiated rectal adenocarcinoma, mismatch repair proficient
MRI stage: * cT1 not eligible for transanal surgery alone as per National Comprehensive Cancer Network (NCCN) guidelines, (including but not limited to T1 tumours > 2 cm in size, positive margin, tumour depth SM3 invasion to the lower third of the submucosal level). or * cT2
cN0 stage based on pelvic MRI including absence of radiographic evidence of mesorectal nodal metastasis, tumour deposits or extramural venous invasion (EMVI)
M0 stage based on no evidence of metastatic disease by CT imaging of chest, abdomen and pelvis
Mid to low-lying tumour eligible for transanal excision in the opinion of the treating surgeon
Medically fit to undergo radical TME surgery as per treating surgeons decision
Participant is able (i.e. sufficiently fluent) and willing to complete the quality of life questionnaires in either English or French or Spanish. The baseline assessment must be completed within required timelines, prior to enrollment. Inability (lack of comprehension in English or French or Spanish, or other equivalent reason such as cognitive issues or lack of competency) to complete the questionnaires will not make the participant ineligible for the study. However, ability but unwillingness to complete the questionnaires will make the participant ineligible
Age of at least 18 years
No contraindications to protocol chemotherapy
Absolute neutrophil count (ANC) 1.5 x 10^9/L (must be done within 30 days prior to enrollment)
Platelet count 100 x 10^9/L (must be done within 30 days prior to enrollment)
Bilirubin 1.5 upper limit of normal (ULN), excluding Gilberts syndrome (must be done within 30 days prior to enrollment)
Estimated creatinine clearance of 50 ml/min (must be done within 30 days prior to enrollment)
The patient must have an Eastern Cooperative Oncology Group (ECOG) performance status of 2 (or Karnofsky 60%)
Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrollment in the trial to document their willingness to participate
Must be accessible for treatment and follow up. Investigators must assure themselves the patients enrolled on this trial will be available for complete documentation of the treatment, adverse events, follow-up and response assessments
Patients must agree to return to their primary care facility for any adverse events which may occur through the course of the trial
Women/men of childbearing potential must have agreed to use a highly effective contraceptive method during and for 6 months after completion of chemotherapy. A woman is considered to be of "childbearing potential" if she has had menses at any time in the preceding 12 consecutive months. In addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation, or vasectomy/vasectomized partner. However, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures
Women of childbearing potential will have a pregnancy test to determine eligibility as part of the pre-study evaluation; this may include an ultrasound to rule-out pregnancy if a false-positive is suspected
Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
Exclusion Criteria:
Pathologic high-risk factors on diagnostic biopsy: high histologic grade (poorly differentiated), mucinous or signet ring histology, lymphatic/vascular or perineural invasion
Patients with visible pelvic sidewall nodes on MRI
Patients with unequivocal determination of nodal disease that, in the opinion of the investigator, would prohibit protocol therapy administration
Previous pelvic radiation for any reason, including brachytherapy alone
Patients who have had primary lesion excised prior to enrollment
Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
Prior treatment for rectal cancer
Patients with known dihydropyrimidine dehydrogenase deficiency (DYPD)
Potential trial participants should have recovered from clinically significant adverse events of their most recent therapy/intervention prior to enrollment
Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better
Any contra-indications to undergo MRI imaging
Presence of anterior lesions above or near peritoneal reflection rendering the patient ineligible for a transanal tumour excision
