Trial Outcomes & Findings for Neo-adjuvant Chemoradiation With Oxaliplatin/5-FU in Rectal Cancer (NCT NCT00831181)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

27 participants

Primary outcome timeframe

Total mesorectal excision (TME) participants were evaluated at the time of surgical resection, an average of 3.5 months

Results posted on

2018-03-20

Participant Flow

Subjects were recruited from 2004-2009 from the oncology practice at Beth Israel and Roosevelt Hospitals.

Participant milestones

Participant milestones
Measure	Oxaliplatin/5-FU Followed by Mesorectal Excision and FOLFOX 6 Preoperative Chemoradiation with oxaliplatin/5-FU followed by mesorectal excision and FOLFOX 6: Preoperative therapy: Oxaliplatin 60 mg/m2 weekly dosing during radiation with continuous infusion 5-FU 225 mg/m2/d Monday through Friday for a total of 96 hours per week each week of radiation (approximately 6-7 weeks). Radiation dose will be 50-54Gy with possible intraoperative (IORT) radiation (10-12Gy). Surgery: Total Mesorectal Excision Postoperative therapy: FOLFOX6 every 2 weeks for 6 cycles (3 months)
Overall Study STARTED	27
Overall Study COMPLETED	15
Overall Study NOT COMPLETED	12

Reasons for withdrawal

Reasons for withdrawal
Measure	Oxaliplatin/5-FU Followed by Mesorectal Excision and FOLFOX 6 Preoperative Chemoradiation with oxaliplatin/5-FU followed by mesorectal excision and FOLFOX 6: Preoperative therapy: Oxaliplatin 60 mg/m2 weekly dosing during radiation with continuous infusion 5-FU 225 mg/m2/d Monday through Friday for a total of 96 hours per week each week of radiation (approximately 6-7 weeks). Radiation dose will be 50-54Gy with possible intraoperative (IORT) radiation (10-12Gy). Surgery: Total Mesorectal Excision Postoperative therapy: FOLFOX6 every 2 weeks for 6 cycles (3 months)
Overall Study Adverse Event	12

Baseline Characteristics

Neo-adjuvant Chemoradiation With Oxaliplatin/5-FU in Rectal Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Chemoradiation,Surgery, Chemotherapy n=27 Participants Preoperative Chemoradiation with oxaliplatin/5-FU followed by mesorectal excision and FOLFOX 6
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	16 Participants n=5 Participants
Age, Categorical >=65 years	11 Participants n=5 Participants
Age, Continuous	60.3 years STANDARD_DEVIATION 10.5 • n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants
Sex: Female, Male Male	17 Participants n=5 Participants
Region of Enrollment United States	27 participants n=5 Participants

PRIMARY outcome

Timeframe: Total mesorectal excision (TME) participants were evaluated at the time of surgical resection, an average of 3.5 months

Population: Number of subjects undergoing TME

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.

Outcome measures

Outcome measures
Measure	Chemoradiation,Surgery, Chemotherapy n=23 Participants Preoperative Chemoradiation with oxaliplatin/5-FU followed by mesorectal excision and FOLFOX 6
Pathologic Response and Complete Response	3 Participants

SECONDARY outcome

Timeframe: Weekly during chemoradiation treatment (3 months). Bi-weekly during adjuvant FOLFOX therapy (3.5 months).

Population: According to the citation J Clin Oncol 28,2010 (suppl; abstract e14128): acute grade 3-4 toxicities occurred in 16 patients, mainly hypersensitivity reactions and OXA associated peripheral neuropathy.

Toxicity was assessed weekly during neoadjuvant chemotherapy and radiation therapy, bi-weekly during adjuvant FOLFOX therapy.

Outcome measures

Outcome measures
Measure	Chemoradiation,Surgery, Chemotherapy n=27 Participants Preoperative Chemoradiation with oxaliplatin/5-FU followed by mesorectal excision and FOLFOX 6
Treatment Toxicity	16 patients

SECONDARY outcome

Timeframe: Total mesorectal excision (TME) participants were evaluated at the time of surgical resection, 3 months after beginning of chemoradiation treatment.

Population: Out of the 27 patients enrolled, a total 23 underwent TME.

Complete resectability rates assessed by circumferential margin.

Outcome measures

Outcome measures
Measure	Chemoradiation,Surgery, Chemotherapy n=23 Participants Preoperative Chemoradiation with oxaliplatin/5-FU followed by mesorectal excision and FOLFOX 6
Complete Resectability Rates	3 patient

SECONDARY outcome

Timeframe: median follow-up 22 months post-TME

Population: Out of the 27 patients enrolled, a total 23 underwent TME and were assessed for local regional control.

subjects were followed for median of 22 months post-surgery

Outcome measures

Outcome measures
Measure	Chemoradiation,Surgery, Chemotherapy n=23 Participants Preoperative Chemoradiation with oxaliplatin/5-FU followed by mesorectal excision and FOLFOX 6
Local Regional Control	21 patient

SECONDARY outcome

Timeframe: median 22 months follow-up

Population: Out of the 27 patients enrolled, a total 23 underwent TME and were assessed for disease-free survival.

Outcome measures

Outcome measures
Measure	Chemoradiation,Surgery, Chemotherapy n=23 Participants Preoperative Chemoradiation with oxaliplatin/5-FU followed by mesorectal excision and FOLFOX 6
Disease-free Survival	16 participants

SECONDARY outcome

Timeframe: median follow-up 22 months

Population: Patients who completed treatment

Outcome measures

Outcome measures
Measure	Chemoradiation,Surgery, Chemotherapy n=23 Participants Preoperative Chemoradiation with oxaliplatin/5-FU followed by mesorectal excision and FOLFOX 6
Overall Survival	21 participants

SECONDARY outcome

Timeframe: median follow-up 22 months

Population: Out of the 27 patients enrolled, a total 23 underwent TME and were assessed for patterns of disease failure.

Outcome measures

Outcome measures
Measure	Chemoradiation,Surgery, Chemotherapy n=23 Participants Preoperative Chemoradiation with oxaliplatin/5-FU followed by mesorectal excision and FOLFOX 6
Patterns of Disease Failure, Including Local Recurrence and Distant Metastasis Assessed by CT Scan	2 patients

SECONDARY outcome

Timeframe: Total mesorectal excision (TME) participants were evaluated at the time of surgical resection, 3 months after beginning of chemoradiation treatment.

Population: Out of the 27 patients enrolled, a total 23 underwent TME. These 23 patients were included for comparison of preoperative stage and post-treatment pathologic stage.

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.

Outcome measures

Outcome measures
Measure	Chemoradiation,Surgery, Chemotherapy n=23 Participants Preoperative Chemoradiation with oxaliplatin/5-FU followed by mesorectal excision and FOLFOX 6
Number of Participants With Comparison of Preoperative Stage With Post-treatment Pathologic Stage	13 patient

Adverse Events

Chemoradiation,Surgery, Chemotherapy

Serious events: 16 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Chemoradiation,Surgery, Chemotherapy n=27 participants at risk Preoperative Chemoradiation with oxaliplatin/5-FU followed by mesorectal excision and FOLFOX 6
Nervous system disorders peripheral neuropathy	37.0% 10/27 • Number of events 10
Immune system disorders oxaliplatin intolerance	22.2% 6/27 • Number of events 6

Other adverse events

Adverse event data not reported

Additional Information

Dr Peter Kozuch

Beth Israel Medical Center

Phone: 212 844-8282

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place