Neo-adjuvant Chemoradiation With Oxaliplatin/5-FU in Rectal Cancer
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT00831181|
Recruitment Status : Completed
First Posted : January 28, 2009
Results First Posted : March 20, 2018
Last Update Posted : March 20, 2018
RATIONALE: 5FU based neoadjuvant chemoradiation (nCRT) is the standard of care for Stage II/III rectal cancer. Pathologic complete response (pCR) and downstaging have been associated with improved outcomes. The addition of oxaliplatin (OXA) to neoadjuvant therapy may reduce distant disease recurrence. Adjuvant treatment with OXA for rectal cancer has been motivated by benefits demonstrated in stage III colon cancer.
Objective: To determine the feasibility, toxicity, and efficacy of preoperative OXA/5FU and RT followed by total mesorectal excision (TME) and adjuvant
PURPOSE: This phase II trial is studying the side effects and how well giving neo-adjuvant combination chemotherapy with radiation works in treating patients undergoing surgery for rectal cancer.
|Condition or disease||Intervention/treatment||Phase|
|Colorectal Cancer||Drug: 5-FU Drug: Oxaliplatin Drug: leucovorin Procedure: mesorectal excision||Phase 2|
- To assess the complete pathologic response rate in patients with rectal cancer treated with radiation, modified neoadjuvant FOLFOX 6 chemotherapy followed by total mesorectal excision and adjuvant modified FOLFOX 6 chemotherapy.
- To observe the overall pathologic response rate in these patients.
- To correlate pathologic staging with preoperative ultrasound and pelvic MRI staging.
- To assess toxic side effects of these regimens in these patients.
- To assess patterns of disease relapse, disease-free survival outcomes, and overall survival outcomes of these patients.
Patients with stage II/III rectal cancer were treated with OXA 60mg/m2 weekly continuous infusion 5FU of 225 mg/m2/d d1-5 with pelvic RT of 1.8Gy/d for 28 doses. Adjuvant therapy consisted of 6 cycles of biweekly FOLFOX6.
Surgery: Patients undergo total mesorectal excision by anterior resection or an abdominal perineal resection within 4 weeks after completion of neoadjuvant therapy.
Adjuvant therapy: Within 4 weeks after surgery, patients receive modified FOLFOX 6 chemotherapy comprising oxaliplatin and leucovorin calcium IV over 2 hours on day 1 and continuous fluorouracil IV over 46 hours on days 1-2. Treatment repeats every 14 days for 6 courses in the absence of disease progression or unacceptable toxicity.
Patients complete quality of life assessment questionnaires at baseline and at each follow-up visit.
After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 3 years, and annually thereafter.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||27 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Open-labeled, Prospective Study to Determine the Efficacy of Preoperative Chemoradiation With Oxaliplatin/5-FU in Locally Advanced Rectal Cancer Followed by Total Mesorectal Excision and FOLFOX6|
|Study Start Date :||July 2004|
|Actual Primary Completion Date :||November 2009|
|Actual Study Completion Date :||November 2009|
Experimental: Preoperative Chemoradiation
Preoperative Chemoradiation with oxaliplatin/5-FU followed by mesorectal excision and 5-FU / leucovorin (FOLFOX 6)
5-FU: continuous infusion via portable pump during all RT (approximately 33 days)
Other Name: fluorouracilDrug: Oxaliplatin
Oxaliplatin: 50mg/m2 weekly dosing during RT (Day 1)
Other Name: EloxatinDrug: leucovorin
Folinic Acid (Leucovorin): 400 mg/m2; 2-hour IV infusion simultaneously with oxaliplatin
Other Name: Folinic AcidProcedure: mesorectal excision
- Pathologic Response and Complete Response [ Time Frame: Total mesorectal excision (TME) participants were evaluated at the time of surgical resection, an average of 3.5 months ]
Pathologic Response and Complete Response to preoperative therapy will be determined at the time of surgical resection. All grossly visible areas of ulceration and/or induration with be measured and submitted for histological evaluation.
The unit of measure is the tumor response rate to preoperative chemoradiation.
Pathologic complete response (pCR) is defined as no evidence of invasive tumor cells on pathologic examination of the primary rectal cancer.
Tumor regression grade (TRG) will be quantitated into five grades:
TRG 1 (complete regression) -absence of residual cancer and fibrosis extending from the site of original tumor through the layers of the rectal wall.
TRG 2 characterized by the presence of rare residual cancer cells scattered through the fibrosis.
TRG 3 characterized by an increase in the number of residual cancer cells, but fibrosis still predominant.
TRG 4 -residual cancer outgrowing fibrosis. TRG 5 characterized by absence of regressive changes.
- Treatment Toxicity [ Time Frame: Weekly during chemoradiation treatment (3 months). Bi-weekly during adjuvant FOLFOX therapy (3.5 months). ]Toxicity was assessed weekly during neoadjuvant chemotherapy and radiation therapy, bi-weekly during adjuvant FOLFOX therapy.
- Complete Resectability Rates [ Time Frame: Total mesorectal excision (TME) participants were evaluated at the time of surgical resection, 3 months after beginning of chemoradiation treatment. ]Complete resectability rates assessed by circumferential margin.
- Local Regional Control [ Time Frame: median follow-up 22 months post-TME ]subjects were followed for median of 22 months post-surgery
- Disease-free Survival [ Time Frame: median 22 months follow-up ]
- Overall Survival [ Time Frame: median follow-up 22 months ]
- Patterns of Disease Failure, Including Local Recurrence and Distant Metastasis Assessed by CT Scan [ Time Frame: median follow-up 22 months ]
- Number of Participants With Comparison of Preoperative Stage With Post-treatment Pathologic Stage [ Time Frame: Total mesorectal excision (TME) participants were evaluated at the time of surgical resection, 3 months after beginning of chemoradiation treatment. ]Thin-section high resolution pelvic MRI was used to image the tumor prior to chemoradiation and repeated prior to surgery, and then compared to post-treatment pathological stage.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00831181
|United States, New York|
|Beth Israel Medical Center - Philipps Ambulatory Care Center|
|New York, New York, United States, 10003|
|St. Luke's-Roosevelt Hospital Center - Roosevelt Division|
|New York, New York, United States, 10019|
|Principal Investigator:||Peter Kozuch, MD||Beth Israel Medical Center|