Altered Chemotherapy Sequencing During Neoadjuvant Therapy for Patients With Stage II or III Rectal Adenocarcinoma
The primary objective of the pilot portion of this study is to establish the safety and tolerability of an extended treatment break period in patients who have undergone neoadjuvant chemoradiotherapy as well as use of systemic therapy during this break.
Stage II Rectal Cancer
Stage III Rectal Cancer
Procedure: total mesorectal excision
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Pilot and Phase II Study of Altered Chemotherapy Sequencing During Neoadjuvant Therapy for Patients With Stage II or III Rectal Adenocarcinoma|
- The primary study endpoint for the phase I portion of this study is to assess surgical complications through the Clavien grading system. [ Time Frame: 90 days ] [ Designated as safety issue: Yes ]The adverse events will be followed prospectively from the date of surgery for 90 days. Dose-limiting toxicity (DLT) will be defined as > grade 3 anastomotic stricture or leak, infection (including pelvic abscess or wound infection), small bowel obstruction, or fistualization. Any other post-operative complication thought related directly to the surgical intervention that is a grade 3 or higher Clavien complication will also be considered dose-limiting toxicity.
- The primary endpoint of the phase II portion of the study is complete pathologic response. [ Time Frame: 9 to 11 weeks ] [ Designated as safety issue: No ]9 to 11 weeks after the completion of the initial chemoradiotherapy.
|Study Start Date:||March 2011|
|Estimated Study Completion Date:||March 2016|
|Estimated Primary Completion Date:||March 2016 (Final data collection date for primary outcome measure)|
RT + Chemo + surgery
Capecitabine will be delivered concurrently with the radiation therapy, at a dose of 1650 mg/m2 divided in even BID doses. It will only be taken on the days of radiation treatment (Monday-Friday, except for holidays). The A.M. dose of the capecitabine must be taken at least one hour prior to the radiation treatment.Drug: 5-FU
5-FU 400 mg/m2, iv bolus on day 1 followed by 2400 mg/m2 iv over 46 hours of each cycle. A cycle is delivered every two weeks. Three cycles will be given prior to the surgery. Five additional cycles will be given after surgery.Drug: Leucovorin
Leucovorin 400 mg/m2, IV, over 2 hours before 5-FU on day 1 of each cycle. A cycle is delivered every two weeks. Three cycles will be given prior to the surgery. Five additional cycles will be given after surgery.Drug: Oxaliplatin
Oxaliplatin 85mg/m2 IV on day 1 of each cycle. A cycle is delivered every two weeks. Three cycles will be given prior to the surgery. Five additional cycles will be given after surgery.Radiation: radiation
28-30 fractions of radiation, given once a day, five days per week (Monday-Friday, except for holidays). The prescribed fraction dose is 180 cGy; the total radiation dose is thus 5040-5400 cGy. The primary treatment fields will be treated with 25 fractions of 180 cGy/fraction with a "boost" of 3-5 fractions of 180 cGy subsequently delivered.Procedure: total mesorectal excision
Optimal surgical technique involving use of total mesorectal excision (TME) is mandated. The type of surgery, either low anterior resection with sparing of the sphincter mechanism or sphincter-eliminating abdominoperineal resection (APR), will be at the discretion of the attending surgeon.
The proposed protocol aims to continue tumor-directed therapy during the typical "break period" in an effort to improve on both local tumor response as well as distant disease control. First, the duration from completion of chemoradiotherapy would increase from 6-8 weeks to 9-11 weeks. As noted above, this may allow for further cell death with resultant pathologic downstaging. Secondly, the protocol calls for continued systemic therapy during the 9-11 week period, thus allowing continuation of therapies directed towards both the primary as well as distant sites of disease. The primary aim of this pilot study would be to establish the feasibility of this intensified neoadjuvant approach, especially with respect to tolerability of the subsequent pelvic surgery. A subsequent phase II portion will evaluate the efficacy of this treatment approach.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01302613
|United States, Texas|
|UT Southwestern Medical Center|
|Dallas, Texas, United States, 75390|
|Principal Investigator:||Jeffrey Meyer, MD||UT Southwestern Medical Center Dallas|