Trial Outcomes & Findings for Pre-op Rectal ChemoRad +/- Cetuximab (NCT NCT00527111)

Last Updated: 2016-11-03

Results Overview

A pathologic complete response (pCR) is defined as no pathologic evidence of invasive disease at the primary site in the bowel wall or in examined mesorectal tissue and/or lymph nodes.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

139 participants

Primary outcome timeframe

5 years

Results posted on

2016-11-03

Participant Flow

Participant milestones

Participant milestones
Measure	Chemoradiotherapy Plus Cetuximab Pelvic irradiation plus 5-fluorouracil plus cetuximab Cetuximab 5-fluorouracil Pelvic irradiation	Chemoradiotherapy Alone Pelvic irradiation plus 5-fluorouracil 5-fluorouracil Pelvic irradiation
Overall Study STARTED	70	69
Overall Study COMPLETED	50	47
Overall Study NOT COMPLETED	20	22

Reasons for withdrawal

Reasons for withdrawal
Measure	Chemoradiotherapy Plus Cetuximab Pelvic irradiation plus 5-fluorouracil plus cetuximab Cetuximab 5-fluorouracil Pelvic irradiation	Chemoradiotherapy Alone Pelvic irradiation plus 5-fluorouracil 5-fluorouracil Pelvic irradiation
Overall Study Adverse Event	14	13
Overall Study Death	0	1
Overall Study Investigator Request	2	1
Overall Study Patient Request	2	5
Overall Study Other	2	2

Baseline Characteristics

Pre-op Rectal ChemoRad +/- Cetuximab

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Chemoradiotherapy Plus Cetuximab n=70 Participants Pelvic irradiation plus 5-fluorouracil plus cetuximab Cetuximab 5-fluorouracil Pelvic irradiation	Chemoradiotherapy Alone n=69 Participants Pelvic irradiation plus 5-fluorouracil 5-fluorouracil Pelvic irradiation	Total n=139 Participants Total of all reporting groups
Age, Continuous	55.9 years STANDARD_DEVIATION 11.0 • n=5 Participants	61.4 years STANDARD_DEVIATION 11.7 • n=7 Participants	58.6 years STANDARD_DEVIATION 11.3 • n=5 Participants
Sex: Female, Male Female	26 Participants n=5 Participants	21 Participants n=7 Participants	47 Participants n=5 Participants
Sex: Female, Male Male	44 Participants n=5 Participants	48 Participants n=7 Participants	92 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	59 participants n=5 Participants	60 participants n=7 Participants	119 participants n=5 Participants
Race/Ethnicity, Customized Black	8 participants n=5 Participants	4 participants n=7 Participants	12 participants n=5 Participants
Race/Ethnicity, Customized Hispanic	1 participants n=5 Participants	3 participants n=7 Participants	4 participants n=5 Participants
Race/Ethnicity, Customized Asian	2 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants
Race/Ethnicity, Customized Other	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Region of Enrollment United States	70 participants n=5 Participants	69 participants n=7 Participants	139 participants n=5 Participants

PRIMARY outcome

Timeframe: 5 years

Population: Post surgery population

A pathologic complete response (pCR) is defined as no pathologic evidence of invasive disease at the primary site in the bowel wall or in examined mesorectal tissue and/or lymph nodes.

Outcome measures

Outcome measures
Measure	Chemoradiotherapy Plus Cetuximab n=64 Participants Pelvic irradiation plus 5-fluorouracil plus cetuximab Cetuximab 5-fluorouracil Pelvic irradiation	Chemoradiotherapy Alone n=60 Participants Pelvic irradiation plus 5-fluorouracil 5-fluorouracil Pelvic irradiation
Percentage of Pathologic Response Rate (pCR) With 95% Confidence Interval.	26.6 percentage of participants Interval 16.3 to 39.1	26.7 percentage of participants Interval 16.1 to 39.7

SECONDARY outcome

Timeframe: 5 years

Population: Evaluable Population

Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions taking as reference the baseline sum LD.

Outcome measures

Outcome measures
Measure	Chemoradiotherapy Plus Cetuximab n=67 Participants Pelvic irradiation plus 5-fluorouracil plus cetuximab Cetuximab 5-fluorouracil Pelvic irradiation	Chemoradiotherapy Alone n=62 Participants Pelvic irradiation plus 5-fluorouracil 5-fluorouracil Pelvic irradiation
To Determine Objective Response Rate (ORR) Based on RECIST Local Recurrence-free Survival in These Patient Groups; Overall and Recurrence-free Survival in These Cohorts.	52.2 percentage of participants Interval 39.7 to 64.6	43.5 percentage of participants Interval 31.0 to 56.7

SECONDARY outcome

Timeframe: 5 years

Population: ITT population

Overall survival is measured from the date of randomization to the date of death for a dead patient. If a patient is still alive or is lost to follow up, the patient will be censored at the date of last contact.

Outcome measures

Outcome measures
Measure	Chemoradiotherapy Plus Cetuximab n=70 Participants Pelvic irradiation plus 5-fluorouracil plus cetuximab Cetuximab 5-fluorouracil Pelvic irradiation	Chemoradiotherapy Alone n=69 Participants Pelvic irradiation plus 5-fluorouracil 5-fluorouracil Pelvic irradiation
5- Year Overall Survival (OS) Rate	0.81 probability of overall survival Interval 0.69 to 0.89	0.68 probability of overall survival Interval 0.53 to 0.79

SECONDARY outcome

Timeframe: 5 years

Population: ITT population

RFS is measured from the date of randomization to the date of first documented disease recurrence or date of death, whichever comes first. If a patient neither recurrences nor dies, this patient will be censored at the date of last contact.

Outcome measures

Outcome measures
Measure	Chemoradiotherapy Plus Cetuximab n=70 Participants Pelvic irradiation plus 5-fluorouracil plus cetuximab Cetuximab 5-fluorouracil Pelvic irradiation	Chemoradiotherapy Alone n=69 Participants Pelvic irradiation plus 5-fluorouracil 5-fluorouracil Pelvic irradiation
Recurrence-free Survival (RFS) Rate at 5 Years	0.65 probability of recurrence-free survival Interval 0.51 to 0.76	0.585 probability of recurrence-free survival Interval 0.44 to 0.71

SECONDARY outcome

Timeframe: 5 years

Population: ITT population with KRAS test

Percentage of Participants with KRAS mutation.

Outcome measures

Outcome measures
Measure	Chemoradiotherapy Plus Cetuximab n=40 Participants Pelvic irradiation plus 5-fluorouracil plus cetuximab Cetuximab 5-fluorouracil Pelvic irradiation	Chemoradiotherapy Alone n=34 Participants Pelvic irradiation plus 5-fluorouracil 5-fluorouracil Pelvic irradiation
KRAS Mutation Rate	32.5 percentage of participants with mutation	44.0 percentage of participants with mutation

Adverse Events

Chemoradiotherapy Plus Cetuximab

Serious events: 10 serious events

Other events: 61 other events

Deaths: 0 deaths

Chemoradiotherapy Alone

Serious events: 5 serious events

Other events: 47 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Chemoradiotherapy Plus Cetuximab n=67 participants at risk Pelvic irradiation plus 5-fluorouracil plus cetuximab Cetuximab 5-fluorouracil Pelvic irradiation	Chemoradiotherapy Alone n=62 participants at risk Pelvic irradiation plus 5-fluorouracil 5-fluorouracil Pelvic irradiation
Gastrointestinal disorders ABDOMINAL PAIN	1.5% 1/67 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.	1.6% 1/62 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.
Gastrointestinal disorders COLITIS	1.5% 1/67 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.	0.00% 0/62 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.
Gastrointestinal disorders DEHYDRATION	7.5% 5/67 • Number of events 5 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.	3.2% 2/62 • Number of events 2 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.
Gastrointestinal disorders DIARRHEA	7.5% 5/67 • Number of events 5 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.	1.6% 1/62 • Number of events 2 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.
Gastrointestinal disorders ENTERITIS	0.00% 0/67 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.	1.6% 1/62 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.
General disorders FEVER	1.5% 1/67 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.	0.00% 0/62 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.
Infections and infestations MUCOSITIS	1.5% 1/67 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.	3.2% 2/62 • Number of events 2 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.
Gastrointestinal disorders NAUSEA	1.5% 1/67 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.	0.00% 0/62 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.
Infections and infestations SEPSIS	3.0% 2/67 • Number of events 3 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.	0.00% 0/62 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.
Gastrointestinal disorders SWALLOWING PAINFUL	0.00% 0/67 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.	1.6% 1/62 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.
Cardiac disorders TACHYCARDIA ATRIAL	1.5% 1/67 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.	0.00% 0/62 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.
Blood and lymphatic system disorders VOLUME BLOOD DECREASED	1.5% 1/67 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.	0.00% 0/62 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.
General disorders WEAKNESS GENERALIZED	0.00% 0/67 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.	1.6% 1/62 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.

Other adverse events

Additional Information

Dr. David McCollum

US Oncology Network, McKesson Specialty Health

Phone: 214-370-1080

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Chemoradiotherapy Plus Cetuximab n=67 participants at risk Pelvic irradiation plus 5-fluorouracil plus cetuximab Cetuximab 5-fluorouracil Pelvic irradiation	Chemoradiotherapy Alone n=62 participants at risk Pelvic irradiation plus 5-fluorouracil 5-fluorouracil Pelvic irradiation
Gastrointestinal disorders ABDOMINAL PAIN	7.5% 5/67 • Number of events 6 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.	12.9% 8/62 • Number of events 8 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.
Blood and lymphatic system disorders ANEMIA	7.5% 5/67 • Number of events 6 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.	9.7% 6/62 • Number of events 8 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.
Gastrointestinal disorders ANOREXIA	23.9% 16/67 • Number of events 19 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.	21.0% 13/62 • Number of events 15 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.
General disorders CHILLS	10.4% 7/67 • Number of events 7 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.	1.6% 1/62 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.
Gastrointestinal disorders CONSTIPATION	11.9% 8/67 • Number of events 9 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.	8.1% 5/62 • Number of events 5 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.
Gastrointestinal disorders DEHYDRATION	10.4% 7/67 • Number of events 8 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.	12.9% 8/62 • Number of events 13 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.
Gastrointestinal disorders DIARRHEA	53.7% 36/67 • Number of events 67 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.	53.2% 33/62 • Number of events 60 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.
Skin and subcutaneous tissue disorders DRY SKIN	7.5% 5/67 • Number of events 6 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.	0.00% 0/62 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.
General disorders FEVER	9.0% 6/67 • Number of events 6 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.	0.00% 0/62 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.
Skin and subcutaneous tissue disorders HAND-FOOT SYNDROME	3.0% 2/67 • Number of events 4 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.	14.5% 9/62 • Number of events 14 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.
General disorders HEADACHE	19.4% 13/67 • Number of events 14 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.	1.6% 1/62 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.
Metabolism and nutrition disorders HYPOKALEMIA	10.4% 7/67 • Number of events 11 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.	1.6% 1/62 • Number of events 1 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.
Metabolism and nutrition disorders HYPOMAGNESAEMIA	14.9% 10/67 • Number of events 15 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.	6.5% 4/62 • Number of events 4 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.
Blood and lymphatic system disorders LEUCOPENIA	6.0% 4/67 • Number of events 4 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.	8.1% 5/62 • Number of events 10 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.
Infections and infestations MUCOSAL SORES	6.0% 4/67 • Number of events 5 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.	8.1% 5/62 • Number of events 5 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.
Infections and infestations MUCOSITIS	28.4% 19/67 • Number of events 25 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.	19.4% 12/62 • Number of events 21 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.
Musculoskeletal and connective tissue disorders MUSCLE WEAKNESS	3.0% 2/67 • Number of events 3 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.	6.5% 4/62 • Number of events 5 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.
Gastrointestinal disorders NAUSEA	26.9% 18/67 • Number of events 22 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.	21.0% 13/62 • Number of events 22 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.
Blood and lymphatic system disorders NEUTROPENIA	7.5% 5/67 • Number of events 6 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.	6.5% 4/62 • Number of events 7 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.
General disorders PAIN	4.5% 3/67 • Number of events 4 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.	9.7% 6/62 • Number of events 6 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.
Skin and subcutaneous tissue disorders RASH	74.6% 50/67 • Number of events 99 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.	8.1% 5/62 • Number of events 5 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.
Gastrointestinal disorders STOMATITIS	7.5% 5/67 • Number of events 6 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.	8.1% 5/62 • Number of events 6 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.
Gastrointestinal disorders VOMITING	9.0% 6/67 • Number of events 7 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.	8.1% 5/62 • Number of events 7 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.
General disorders WEAKNESS	37.3% 25/67 • Number of events 31 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.	30.6% 19/62 • Number of events 20 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.
General disorders WEIGHT LOSS	10.4% 7/67 • Number of events 8 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.	4.8% 3/62 • Number of events 3 • During the whole treatment period, up to 30 days following last dose. For treatment patients only, assessed at each treatment visit.