Trial Outcomes & Findings for A Clinical Trial of COX and EGFR Inhibition in Familial Polyposis Patients (NCT NCT01187901)

NCT ID: NCT01187901

Last Updated: 2016-06-17

Results Overview

A comparison between the Sulindac-erlotinib and Placebo arms of the change in polyp burden from a 10-centimeter segment of the duodenum, measured as the sum of the diameters of the polyps, in millimeters (mm), from the duodenal segment (6-month polyp burden minus baseline polyp burden).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

92 participants

Primary outcome timeframe

Baseline and 6 months

Results posted on

2016-06-17

Participant Flow

Participant milestones

Participant milestones
Measure	Sulindac-erlotinib Sulindac 150 mg twice daily in combination with erlotinib 75 mg per day for 6 months	Placebo Placebo capsules matching erlotinib active comparator (Placebo A) once daily and placebo capsules matching sulindac active comparator (Placebo B) twice daily for 6 months
Overall Study STARTED	46	46
Overall Study COMPLETED	37	36
Overall Study NOT COMPLETED	9	10

Reasons for withdrawal

Reasons for withdrawal
Measure	Sulindac-erlotinib Sulindac 150 mg twice daily in combination with erlotinib 75 mg per day for 6 months	Placebo Placebo capsules matching erlotinib active comparator (Placebo A) once daily and placebo capsules matching sulindac active comparator (Placebo B) twice daily for 6 months
Overall Study Protocol Violation	1	0
Overall Study Lost to Follow-up	1	2
Overall Study Unrelated Health Reasons	1	2
Overall Study Suspected Allergic Reaction	1	1
Overall Study Adverse Event	3	0
Overall Study No Endpoint due to Early Study Halt	2	3
Overall Study Pregnancy	0	2

Baseline Characteristics

A Clinical Trial of COX and EGFR Inhibition in Familial Polyposis Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sulindac-erlotinib n=46 Participants Sulindac 150 mg twice daily in combination with erlotinib 75 mg per day for 6 months	Placebo n=46 Participants Placebo capsules matching erlotinib active comparator (Placebo A) once daily and placebo capsules matching sulindac active comparator (Placebo B) twice daily for 6 months	Total n=92 Participants Total of all reporting groups
Age, Continuous	42 years STANDARD_DEVIATION 14 • n=5 Participants	41 years STANDARD_DEVIATION 14 • n=7 Participants	41 years STANDARD_DEVIATION 14 • n=5 Participants
Sex: Female, Male Female	28 Participants n=5 Participants	28 Participants n=7 Participants	56 Participants n=5 Participants
Sex: Female, Male Male	18 Participants n=5 Participants	18 Participants n=7 Participants	36 Participants n=5 Participants
Familial Adenomatous Polyposis (FAP) Status Classic FAP	32 participants n=5 Participants	32 participants n=7 Participants	64 participants n=5 Participants
Familial Adenomatous Polyposis (FAP) Status Attenuated FAP	14 participants n=5 Participants	14 participants n=7 Participants	28 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 6 months

A comparison between the Sulindac-erlotinib and Placebo arms of the change in polyp burden from a 10-centimeter segment of the duodenum, measured as the sum of the diameters of the polyps, in millimeters (mm), from the duodenal segment (6-month polyp burden minus baseline polyp burden).

Outcome measures

Outcome measures
Measure	Sulindac-erlotinib n=46 Participants Sulindac 150 mg twice daily in combination with erlotinib 75 mg per day for 6 months	Placebo n=46 Participants Placebo capsules matching erlotinib active comparator (Placebo A) once daily and placebo capsules matching sulindac active comparator (Placebo B) twice daily for 6 months
Change in Duodenal Polyp Burden From Baseline to 6 Months	-8.5 mm Interval -9.5 to -7.0	8.0 mm Interval 5.0 to 9.5

SECONDARY outcome

Timeframe: Baseline and 6 months

Population: Classic FAP participants are defined as those presenting with more than 100 colonic adenomas and either (1) multiple family members with a classic FAP phenotype or (2) an adenomatous polyposis coli (APC) mutation in a region of the gene known to correlate with Classic FAP, or (3) both.

A comparison between the Sulindac-erlotinib and Placebo arm Classic FAP subgroups of the change in polyp burden from a 10-centimeter segment of the duodenum, measured as the sum of the diameters of the polyps, in millimeters (mm), from the duodenal segment (6-month polyp burden minus baseline polyp burden).

Outcome measures

Outcome measures
Measure	Sulindac-erlotinib n=32 Participants Sulindac 150 mg twice daily in combination with erlotinib 75 mg per day for 6 months	Placebo n=32 Participants Placebo capsules matching erlotinib active comparator (Placebo A) once daily and placebo capsules matching sulindac active comparator (Placebo B) twice daily for 6 months
Change in Duodenal Polyp Burden From Baseline to 6 Months in Classic Familial Adenomatous Polyposis (FAP) Participants	-8.5 mm Interval -9.5 to -7.3	8.5 mm Interval 4.5 to 11.3

SECONDARY outcome

Timeframe: Baseline and 6 months

Population: Attenuated FAP participants are defined with the presence of a mutation in a portion of the adenomatous polyposis coli (APC) gene known to correlate with attenuated FAP and presentation of a milder phenotype in terms of polyp density in the participant and the family. All participants with attenuated FAP had a confirmed mutation in the APC gene.

A comparison between the Sulindac-erlotinib and Placebo arm Attenuated FAP subgroups of the change in polyp burden from a 10-centimeter segment of the duodenum, measured as the sum of the diameters of the polyps, in millimeters (mm), from the duodenal segment (6-month polyp burden minus baseline polyp burden).

Outcome measures

Outcome measures
Measure	Sulindac-erlotinib n=14 Participants Sulindac 150 mg twice daily in combination with erlotinib 75 mg per day for 6 months	Placebo n=14 Participants Placebo capsules matching erlotinib active comparator (Placebo A) once daily and placebo capsules matching sulindac active comparator (Placebo B) twice daily for 6 months
Change in Duodenal Polyp Burden From Baseline to 6 Months in Attenuated FAP Participants	-8.0 mm Interval -9.5 to -5.5	7.0 mm Interval 5.0 to 9.5

SECONDARY outcome

Timeframe: Baseline and 6 months

A comparison between the Sulindac-erlotinib and Placebo arms of the change in number of polyps in a 10-centimeter segment of the duodenum (6-month polyp count minus baseline polyp count).

Outcome measures

Outcome measures
Measure	Sulindac-erlotinib n=46 Participants Sulindac 150 mg twice daily in combination with erlotinib 75 mg per day for 6 months	Placebo n=46 Participants Placebo capsules matching erlotinib active comparator (Placebo A) once daily and placebo capsules matching sulindac active comparator (Placebo B) twice daily for 6 months
Change in Number of Duodenal Polyps From Baseline to 6 Months	-2.8 polyps Interval -4.0 to -1.5	4.3 polyps Interval 3.1 to 5.5

SECONDARY outcome

Timeframe: Baseline and 6 months

Population: Classic FAP participants are defined as those presenting with more than 100 colonic adenomas and either (1) multiple family members with a classic FAP phenotype or (2) an adenomatous polyposis coli (APC) mutation in a region of the gene known to correlate with Classic FAP, or (3) both

A comparison between the Sulindac-erlotinib and Placebo arm Classic FAP subgroups of the change in number of polyps in a 10-centimeter segment of the duodenum (6-month polyp count minus baseline polyp count)

Outcome measures

Outcome measures
Measure	Sulindac-erlotinib n=32 Participants Sulindac 150 mg twice daily in combination with erlotinib 75 mg per day for 6 months	Placebo n=32 Participants Placebo capsules matching erlotinib active comparator (Placebo A) once daily and placebo capsules matching sulindac active comparator (Placebo B) twice daily for 6 months
Change in Number of Duodenal Polyps From Baseline to 6 Months in Classic FAP Participants	-2.1 polyps Interval -4.0 to -0.5	4.0 polyps Interval 2.5 to 5.6

SECONDARY outcome

Timeframe: Baseline and 6 months

Population: Attenuated FAP participants are defined with the presence of a mutation in a portion of the adenomatous polyposis coli (APC) gene known to correlate with attenuated FAP and presentation of a milder phenotype in terms of polyp density in the participant and the family. All participants with attenuated FAP had a confirmed mutation in the APC gene.

A comparison between the Sulindac-erlotinib and Placebo arm Attenuated FAP subgroups of the change in number of polyps in a 10-centimeter segment of the duodenum (6-month polyp count minus baseline polyp count)

Outcome measures

Outcome measures
Measure	Sulindac-erlotinib n=14 Participants Sulindac 150 mg twice daily in combination with erlotinib 75 mg per day for 6 months	Placebo n=14 Participants Placebo capsules matching erlotinib active comparator (Placebo A) once daily and placebo capsules matching sulindac active comparator (Placebo B) twice daily for 6 months
Change in Number of Duodenal Polyps From Baseline to 6 Months in Attenuated FAP Participants	-4.3 polyps Interval -6.0 to -2.5	4.9 polyps Interval 3.6 to 6.0

Adverse Events

Sulindac-erlotinib

Serious events: 0 serious events

Other events: 43 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 33 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Sulindac-erlotinib n=46 participants at risk Sulindac 150 mg twice daily in combination with erlotinib 75 mg per day for 6 months	Placebo n=46 participants at risk Placebo capsules matching erlotinib active comparator (Placebo A) once daily and placebo capsules matching sulindac active comparator (Placebo B) twice daily for 6 months
Skin and subcutaneous tissue disorders Rash Acneiform	87.0% 40/46 • 6 months	19.6% 9/46 • 6 months
Gastrointestinal disorders Oral Mucositis	39.1% 18/46 • 6 months	10.9% 5/46 • 6 months
Gastrointestinal disorders Diarrhea	26.1% 12/46 • 6 months	13.0% 6/46 • 6 months
Gastrointestinal disorders Nausea	23.9% 11/46 • 6 months	13.0% 6/46 • 6 months
Musculoskeletal and connective tissue disorders Pain in Extremity	8.7% 4/46 • 6 months	21.7% 10/46 • 6 months
Skin and subcutaneous tissue disorders Dry Skin	15.2% 7/46 • 6 months	15.2% 7/46 • 6 months
Gastrointestinal disorders Abdominal Pain	8.7% 4/46 • 6 months	17.4% 8/46 • 6 months
Eye disorders Dry Eye	19.6% 9/46 • 6 months	2.2% 1/46 • 6 months
Nervous system disorders Headache	8.7% 4/46 • 6 months	17.4% 8/46 • 6 months
General disorders Fatigue	10.9% 5/46 • 6 months	10.9% 5/46 • 6 months
Skin and subcutaneous tissue disorders Alopecia	10.9% 5/46 • 6 months	2.2% 1/46 • 6 months
Gastrointestinal disorders Dyspepsia	8.7% 4/46 • 6 months	4.3% 2/46 • 6 months
Investigations Aminotransferase Increase	6.5% 3/46 • 6 months	8.7% 4/46 • 6 months
Vascular disorders Hypertension	6.5% 3/46 • 6 months	0.00% 0/46 • 6 months
Gastrointestinal disorders Lower Gastrointestinal Hemorrhage	6.5% 3/46 • 6 months	0.00% 0/46 • 6 months

Additional Information

N. Jewel Samadder

University of Utah

Phone: 801-213-4211

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place