E-Newsletter - June 2018

Results from Alliance Trial May Influence Future Treatment for Patients with Rectal Cancer

N1048 (PROSPECT) A phase II/III trial of neoadjuvant FOLFOX, with selective use of combined modality chemoradiation versus preoperative combined modality chemoradiation for locally advanced rectal cancer patients undergoing low anterior resection with total mesorectal excision

The Alliance trial, N1048, also referred to as PROSPECT (Preoperative Radiation Or Selective Preoperative radiation and Evaluation before Chemotherapy and TME), is a randomized phase II/III trial of the selective use of radiation therapy in intermediate risk clinical stage II-III rectal cancer. 

In this study, Alliance investigators will learn whether radiation can be used selectively rather than consistently for treatment of locally advanced rectal cancer. All patients will undergo surgery. Investigators hypothesize that if patients respond to neoadjuvant chemotherapy (FOLFOX for six cycles), then it may be safe to omit pelvic radiation without compromising outcomes. It is anticipated that this strategy could minimize toxicity without compromising cure rates. However, this must be empirically tested. If radiation is essential, then adjuvant regimens must continue to build upon this backbone. The study is not designed to eliminate radiation, but rather to see if it can be used strategically for those patients who do not respond to neoadjuvant FOLFOX instead of reflexively for all patients. 

N1048 (PROSPECT) is a two-arm study with one to one randomization. The control arm of the study includes standard chemoradiation for rectal cancer. The choice of capecitabine or 5FU for sensitization is up to the treating physician. The intervention arm includes six cycles of neoadjuvant FOLFOX followed by restaging. Patients with clinical response to induction FOLFOX proceed directly to surgery. Those patients with poor response (estimated at less than 20 percent decrease in the tumor burden) will undergo chemoradiation first. In this manner, the intervention arm is a dynamic strategy that includes radiation for tumors that do not respond to FOLFOX and omission of radiation for those that do. 

The ongoing phase III component evaluates clinical outcomes for the co-primary endpoints of disease-free survival and time to local recurrence. 

This study has the potential to personalize rectal cancer therapy and increase the number of available approaches to treatment. It includes quality of life assessments, patient-reported assessments of treatment toxicity, along with biological, immunologic and pharmacogenomic correlative studies. The study has recruited 1,040 of planned 1,180 patients and the goal is to complete recruitment within the next calendar year.

N1048 (PROSPECT) is currently available on the CTSU menu (www.ctsu.org) to all Alliance members and most other network groups. Study chair is Deborah Schrag, MD MPH, Dana-Farber Cancer Institute, e-mail: deb_schrag@dfci.harvard.edu.

ClinicalTrials.gov Identifier: NCT01515787


For other articles in this issue of the Alliance E-News newsletter, see below.