Trial Outcomes & Findings for Vorinostat in Treating Women Who Are Undergoing Surgery For Newly Diagnosed Stage I -III Breast Cancer (NCT NCT00262834)

Results Overview

Participants were evaluated for adverse events due to vorinostat to assess if it was safe to give the drug prior to surgery. 17 of 25 participants who received vorinostat experienced at least 1 adverse event believed to be related to the study drug; no adverse events were severe, and the treatment was considered safe.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

54 participants

Primary outcome timeframe

After 3 days of vorinostat

Results posted on

2020-02-19

Participant Flow

Women enrolled from two sites, Johns Hopkins Medical Institutes and Anne Arundel Medical Center. Informed consent was obtained from all participants in the vorinostat and control groups.

Women must have adequate performance status and blood counts/organ function; no hormones within 30 days of diagnostic biopsy, prior or concomitant treatment for the current cancer, or uncontrolled intercurrent illness that could limit compliance were allowed.

Participant milestones

Participant milestones
Measure	Vorinostat Women in the vorinostat group were scheduled to receive 6 doses of oral vorinostat at 300 mg twice daily (bid), with the last dose administered by study personnel approximately 2 hours before the scheduled breast surgery (or biopsy).	Tissue Only Women who declined vorinostat but agreed to donate tissues for biomarker assessment, signed a separate informed consent and were enrolled as controls.
Overall Study STARTED	25	29
Overall Study COMPLETED	24	25
Overall Study NOT COMPLETED	1	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Vorinostat Women in the vorinostat group were scheduled to receive 6 doses of oral vorinostat at 300 mg twice daily (bid), with the last dose administered by study personnel approximately 2 hours before the scheduled breast surgery (or biopsy).	Tissue Only Women who declined vorinostat but agreed to donate tissues for biomarker assessment, signed a separate informed consent and were enrolled as controls.
Overall Study Surgery delayed/tissue not collected	1	4

Baseline Characteristics

Vorinostat in Treating Women Who Are Undergoing Surgery For Newly Diagnosed Stage I -III Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Vorinostat n=25 Participants Women in the vorinostat group were scheduled to receive 6 doses of oral vorinostat at 300 mg twice daily (bid), with the last dose administered by study personnel approximately 2 hours before the scheduled breast surgery (or biopsy).	Tissue Only n=29 Participants Women who declined vorinostat but agreed to donate tissues for biomarker assessment, signed a separate informed consent and were enrolled as controls.	Total n=54 Participants Total of all reporting groups
Age, Continuous	55 years n=5 Participants	52 years n=7 Participants	54 years n=5 Participants
Age, Customized <=18 years	0 years n=5 Participants	0 years n=7 Participants	0 years n=5 Participants
Age, Customized >18 years	25 years n=5 Participants	29 years n=7 Participants	54 years n=5 Participants
Sex: Female, Male Female	25 Participants n=5 Participants	29 Participants n=7 Participants	54 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	25 participants n=5 Participants	29 participants n=7 Participants	54 participants n=5 Participants

PRIMARY outcome

Timeframe: After 3 days of vorinostat

Population: Participants who received at least one dose of vorinostat.

Participants were evaluated for adverse events due to vorinostat to assess if it was safe to give the drug prior to surgery. 17 of 25 participants who received vorinostat experienced at least 1 adverse event believed to be related to the study drug; no adverse events were severe, and the treatment was considered safe.

Outcome measures

Outcome measures
Measure	Vorinostat n=25 Participants Women in the vorinostat group were scheduled to receive 6 doses of oral vorinostat at 300 mg twice daily (bid), with the last dose administered by study personnel approximately 2 hours before the scheduled breast surgery (or biopsy).	Tissue Only Women who declined vorinostat but agreed to donate tissues for biomarker assessment, signed a separate informed consent and were enrolled as controls.
Number of Participants With Adverse Events	17 participants	—

PRIMARY outcome

Timeframe: After 3 days of vorinostat

Population: Matched samples (ie, diagnostic biopsy and surgical tissues) for Ki-67 by IHC were available from 22 (92%) treated and from 15 (60%) controls.

Change in Ki-67 (a marker of tissue proliferation) by IHC compared to baseline in the treated (22 evaluable samples) or untreated patients (15 evaluable samples) were analyzed between groups. Ki-67 is a protein in cells that increases as cellsprepare to divide into new cells. A staining process can measure the percentage of tumor cells that are positive for Ki-67. The more positive cells there are, the more quickly they are dividing and forming new cells.

Outcome measures

Outcome measures
Measure	Vorinostat n=22 Evaluable tissue samples Women in the vorinostat group were scheduled to receive 6 doses of oral vorinostat at 300 mg twice daily (bid), with the last dose administered by study personnel approximately 2 hours before the scheduled breast surgery (or biopsy).	Tissue Only n=15 Evaluable tissue samples Women who declined vorinostat but agreed to donate tissues for biomarker assessment, signed a separate informed consent and were enrolled as controls.
Change in Tissue Proliferation After 3 Days of Treatment	-3 percentage of change Interval -62.0 to 38.0	-4 percentage of change Interval -32.0 to 46.0

PRIMARY outcome

Timeframe: Baseline and after 3 day of vorinostat

Population: Matched samples (ie, diagnostic biopsy and surgical tissues) for cleaved caspase-3 by IHC were available from 19 (71%) treated and from 12 (48%) controls.

Change in cleaved caspase-3 (a marker of tissue apoptosis) by IHC compared to baseline in the treated (19 evaluable samples) or untreated patients (12 evaluable samples) were analyzed between groups. Cleaved caspase-3 is a protein in cells involved in apoptosis (cell death).

Outcome measures

Outcome measures
Measure	Vorinostat n=19 Evaluable tissue samples Women in the vorinostat group were scheduled to receive 6 doses of oral vorinostat at 300 mg twice daily (bid), with the last dose administered by study personnel approximately 2 hours before the scheduled breast surgery (or biopsy).	Tissue Only n=12 Evaluable tissue samples Women who declined vorinostat but agreed to donate tissues for biomarker assessment, signed a separate informed consent and were enrolled as controls.
Change in Tissue Apoptosis After 3 Days of Treatment	0 percentage of change Interval -5.0 to 5.0	0 percentage of change Interval -2.0 to 3.0

SECONDARY outcome

Timeframe: Baseline and after 3 day of Vorinostat

Population: 25 matched samples were collected; however, only 19 were available for analysis as there were 6 cases that were not evaluable for Cumulative Methylation Index.

To evaluate change from baseline in tissue histone acetylation in patients with primary breast cancer who received three days of Short Term Oral Suberoylanilide Hydroxamic Acid (SAHA) 300 mg PO bid immediately prior to definitive breast surgery or other primary treatment. This is measured by Cumulative Methylation Index, which is reported as the sum of all %M for all genes. %M= (methylated copies divided by methylated + unmethylated copies) x 100.

Outcome measures

Outcome measures
Measure	Vorinostat n=19 Participants Women in the vorinostat group were scheduled to receive 6 doses of oral vorinostat at 300 mg twice daily (bid), with the last dose administered by study personnel approximately 2 hours before the scheduled breast surgery (or biopsy).	Tissue Only Women who declined vorinostat but agreed to donate tissues for biomarker assessment, signed a separate informed consent and were enrolled as controls.
Change in Tissue Histone Acetylation After 3 Days of Treatment	38.3 Cumulative Methylation Index	—

SECONDARY outcome

Timeframe: Baseline and after 3 day of Vorinostat

Population: No data was collected for this outcome. We were not able to successfully dissolve the pellet in lysis buffer, and the samples were not subjected to histone acetylation analyses.

To evaluate baseline and change in histone acetylation in polymononuclear cells in patients with primary breast cancer who received three days of SAHA 300 mg PO bid immediately prior to definitive breast surgery or other primary treatment.

Outcome measures

Outcome data not reported

Adverse Events

Vorinostat

Serious events: 0 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Vorinostat n=25 participants at risk Women in the vorinostat group were scheduled to receive 6 doses of oral vorinostat at 300 mg twice daily (bid), with the last dose administered by study personnel approximately 2 hours before the scheduled breast surgery (or biopsy). Only vortinostat group adverse events were reported or collected to assess association of events with the agent in question.
Gastrointestinal disorders Diarrhea	28.0% 7/25 • Number of events 7 • Baseline and after 3 day of vorinostat Participants were assessed by study staff a specified time points per CTCAE 3.0.
General disorders Fatigue	16.0% 4/25 • Number of events 4 • Baseline and after 3 day of vorinostat Participants were assessed by study staff a specified time points per CTCAE 3.0.
Gastrointestinal disorders Dysgeusia	16.0% 4/25 • Number of events 4 • Baseline and after 3 day of vorinostat Participants were assessed by study staff a specified time points per CTCAE 3.0.
Gastrointestinal disorders Anorexia	12.0% 3/25 • Number of events 3 • Baseline and after 3 day of vorinostat Participants were assessed by study staff a specified time points per CTCAE 3.0.
Gastrointestinal disorders Nausea	16.0% 4/25 • Number of events 4 • Baseline and after 3 day of vorinostat Participants were assessed by study staff a specified time points per CTCAE 3.0.
Nervous system disorders Headache	4.0% 1/25 • Number of events 1 • Baseline and after 3 day of vorinostat Participants were assessed by study staff a specified time points per CTCAE 3.0.
Investigations White blood cell decreased	24.0% 6/25 • Number of events 6 • Baseline and after 3 day of vorinostat Participants were assessed by study staff a specified time points per CTCAE 3.0.

Additional Information

Vered Stearns

SKCCC

Phone: 4432876489

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60