Trial Outcomes & Findings for DNA in Predicting Response After Systemic Therapy in Women With Metastatic Breast Cancer (NCT NCT00899548)

Results Overview

Recruitment status

COMPLETED

Target enrollment

182 participants

Primary outcome timeframe

from week 4 to up to 87 months

Results posted on

2019-07-26

Participant Flow

Participants were recruited at each of the participating institutions at Johns Hopkins and within the Translational Breast Cancer Research Consortium.

Participant milestones

Participant milestones
Measure	Metastatic Breast Cancer Patients Adult women with metastatic breast cancer.
Overall Study STARTED	182
Overall Study COMPLETED	179
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Metastatic Breast Cancer Patients Adult women with metastatic breast cancer.
Overall Study Physician Decision	3

Baseline Characteristics

DNA in Predicting Response After Systemic Therapy in Women With Metastatic Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Metastatic Breast Cancer Patients n=182 Participants Adult women with metastatic breast cancer.
Age, Continuous	56 years n=93 Participants
Sex: Female, Male Female	182 Participants n=93 Participants
Sex: Female, Male Male	0 Participants n=93 Participants
Region of Enrollment United States	182 Participants n=93 Participants

PRIMARY outcome

Timeframe: from week 4 to up to 87 months

Population: 141/179 participants who completed the study were evaluable for this outcome measure. Of these, 8 participants were excluded from analysis for events experienced before week 4, 2 participants had inadequate samples for analysis and data was not collected from 3 participants.

Outcome measures

Outcome measures
Measure	Metastatic Breast Cancer Patients -- CMI High n=71 Participants All subjects enrolled to the study with samples analyzed for the primary objective of DNA methylation in metastatic breast cancer patients who had a high CMI.	Metastatic Breast Cancer Patients -- CMI Low n=57 Participants All subjects enrolled to the study with samples analyzed for the primary objective of DNA methylation in metastatic breast cancer patients who had a low CMI.
Progression-free Survival in Patients With a High vs. Low Cumulative Methylation Index (CMI) Value	2.1 months Interval 1.7 to 3.2	5.8 months Interval 4.7 to 7.4

PRIMARY outcome

Timeframe: baseline, week 4

Population: Data to assess this outcome measure was only collected from 129/182 participants with metastatic breast cancer.

log change in cumulative methylation index (CMI) from baseline to week 4. Individual gene methylation (M) is calculated as a methylation index (MI) where MI = (methylated copies)/(number of methylated genes + gene standard copies) \* 100. The MI of each sample was averaged across duplicates. The cumulative methylation index (CMI) is the sum of the MI for all genes. The log change from based line to week 4 could increase or decrease. CMI was evaluated as a continuous marker for change from baseline.

Outcome measures

Outcome measures
Measure	Metastatic Breast Cancer Patients -- CMI High n=129 Participants All subjects enrolled to the study with samples analyzed for the primary objective of DNA methylation in metastatic breast cancer patients who had a high CMI.	Metastatic Breast Cancer Patients -- CMI Low All subjects enrolled to the study with samples analyzed for the primary objective of DNA methylation in metastatic breast cancer patients who had a low CMI.
Changes in Methylated Gene Markers as Measured by Cumulative Methylation Index	-1.20 log CMI change Standard Deviation 1.84	—

PRIMARY outcome

Timeframe: 9-12 weeks

Population: Data was not collected to assess this outcome measure

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: 9-12 weeks

Population: Data was not collected to assess this outcome measure

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: from week 4 to up to 3 years

Population: 141/179 participants who completed the study were evaluable for this outcome measure. Of these, 7 participants were excluded from analysis for events experienced before week 4, 2 participants had inadequate samples for analysis and data was not collected from 3 participants.

Outcome measures

Outcome measures
Measure	Metastatic Breast Cancer Patients -- CMI High n=62 Participants All subjects enrolled to the study with samples analyzed for the primary objective of DNA methylation in metastatic breast cancer patients who had a high CMI.	Metastatic Breast Cancer Patients -- CMI Low n=67 Participants All subjects enrolled to the study with samples analyzed for the primary objective of DNA methylation in metastatic breast cancer patients who had a low CMI.
Overall Survival in Patients With a High vs. Low CMI Value	12.3 months Interval 8.4 to 16.5	21.7 months Interval 19.3 to 28.3

SECONDARY outcome

Timeframe: 3-4 weeks

Population: Data was not collected for this outcome measure

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: 3-4 weeks

Outcome measures

Outcome data not reported

POST_HOC outcome

Timeframe: 4 weeks

Population: Data for this outcome measure was collected from only 96 participants.

overall survival in participants with high or low cumulative tumor cells (CTC). "high CTC" refers to \>5 cells/7.5mL and "low CTC" refers to \<5 cells/7.5mL.

Outcome measures

Outcome measures
Measure	Metastatic Breast Cancer Patients -- CMI High n=96 Participants All subjects enrolled to the study with samples analyzed for the primary objective of DNA methylation in metastatic breast cancer patients who had a high CMI.	Metastatic Breast Cancer Patients -- CMI Low All subjects enrolled to the study with samples analyzed for the primary objective of DNA methylation in metastatic breast cancer patients who had a low CMI.
Overall Survival in Participants With High CTC vs. Low CTC High CTC (>5 cells/7.5 mL)	8.1 months Interval 4.9 to 18.8	—
Overall Survival in Participants With High CTC vs. Low CTC Low CTC (<5 cells/7.5 mL)	20.8 months Interval 17.5 to 26.6	—

Adverse Events

Metastatic Breast Cancer Patients

Serious events: 3 serious events

Other events: 0 other events

Deaths: 3 deaths

Serious adverse events

Serious adverse events
Measure	Metastatic Breast Cancer Patients n=182 participants at risk Adult women with metastatic breast cancer.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Death	1.6% 3/182 • Number of events 3 • up to 12 weeks from time of consenting to study

Other adverse events

Adverse event data not reported

Additional Information

Antonio C. Wolff, M.D.

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Phone: 410-614-4192

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place