Trial Outcomes & Findings for 2nd Line Treatment With Pemetrexed and Sorafenib for Recurrent or Metastatic Triple Negative Breast Cancer (NCT NCT02624700)

Last Updated: 2020-07-14

Results Overview

The primary endpoint is the percentage of patients with HER2-negative metastatic breast cancer achieving an objective response (either PR or CR). Overall Response = CR+PR, based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1).

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

13 participants

Primary outcome timeframe

2 years 3 months

Results posted on

2020-07-14

Participant Flow

Participant milestones

Participant milestones
Measure	A: Pemetrexed + Sorafenib Pemetrexed 500 mg/m2 IV Day 1 + Sorafenib 400mg PO twice each day on Days 1-5 of each 14-day cycle Experimental Arm A: Pemetrexed: Treatment schedule is administered on day 1 of each 14-day cycle by Intravenous infusion over 10 minutes with a dose of 500 mg/m2. If necessary, the duration of the pemetrexed infusion may be extended to a maximum of 20 minutes. Experimental Arm A: Sorafenib: Treatment schedule is administered twice daily by mouth on an empty stomach on days 1-5 of each 14-day cycle with a dose of 400 mg.	B: Pemetrexed + Sorafenib Pemetrexed 375mg/m2 intravenously (IV) Day 1 + Sorafenib 200mg by mouth twice daily on days 1-5, every 21-days of each cycle. Experimental Arm B: Pemetrexed: Treatment schedule is administered on day 1 of each 21-day cycle by Intravenous infusion over 10 minutes with a dose of 375 mg/m2. If necessary, the duration of the pemetrexed infusion may be extended to a maximum of 20 minutes. Experimental Arm B: Sorafenib: Treatment schedule is administered twice daily by mouth on an empty stomach on days 1-5 of each 21-day cycle with a dose of 200 mg.
Overall Study STARTED	9	4
Overall Study COMPLETED	9	4
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

2nd Line Treatment With Pemetrexed and Sorafenib for Recurrent or Metastatic Triple Negative Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	A: Pemetrexed + Sorafenib n=9 Participants Pemetrexed 500 mg/m2 IV Day 1 + Sorafenib 400mg PO twice each day on Days 1-5 of each 14-day cycle Experimental Arm A: Pemetrexed: Treatment schedule is administered on day 1 of each 14-day cycle by Intravenous infusion over 10 minutes with a dose of 500 mg/m2. If necessary, the duration of the pemetrexed infusion may be extended to a maximum of 20 minutes. Experimental Arm A: Sorafenib: Treatment schedule is administered twice daily by mouth on an empty stomach on days 1-5 of each 14-day cycle with a dose of 400 mg.	B: Pemetrexed + Sorafenib n=4 Participants Pemetrexed 375mg/m2 intravenously (IV) Day 1 + Sorafenib 200mg by mouth twice daily on days 1-5, every 21 days of each cycle. Experimental Arm B: Pemetrexed: Treatment schedule is administered on day 1 of each 21-day cycle by Intravenous infusion over 10 minutes with a dose of 375 mg/m2. If necessary, the duration of the pemetrexed infusion may be extended to a maximum of 20 minutes. Experimental Arm B: Sorafenib: Treatment schedule is administered twice daily by mouth on an empty stomach on days 1-5 of each 21-day cycle with a dose of 200 mg.	Total n=13 Participants Total of all reporting groups
Age, Continuous	54.89 Years n=93 Participants	56.75 Years n=4 Participants	55.46 Years n=27 Participants
Sex: Female, Male Female	9 Participants n=93 Participants	4 Participants n=4 Participants	13 Participants n=27 Participants
Sex: Female, Male Male	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	9 Participants n=93 Participants	4 Participants n=4 Participants	13 Participants n=27 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Black or African American	3 Participants n=93 Participants	1 Participants n=4 Participants	4 Participants n=27 Participants
Race (NIH/OMB) White	6 Participants n=93 Participants	3 Participants n=4 Participants	9 Participants n=27 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants
Region of Enrollment United States	9 participants n=93 Participants	4 participants n=4 Participants	13 participants n=27 Participants

PRIMARY outcome

Timeframe: 2 years 3 months

Outcome measures

Outcome measures
Measure	A: Pemetrexed + Sorafenib n=9 Participants Pemetrexed 500 mg/m2 IV Day 1 + Sorafenib 400mg PO twice each day on Days 1-5 of each 14-day cycle Experimental Arm A: Pemetrexed: Treatment schedule is administered on day 1 of each 14-day cycle by Intravenous infusion over 10 minutes with a dose of 500 mg/m2. If necessary, the duration of the pemetrexed infusion may be extended to a maximum of 20 minutes. Experimental Arm A: Sorafenib: Treatment schedule is administered twice daily by mouth on an empty stomach on days 1-5 of each 14-day cycle with a dose of 400 mg.	B: Pemetrexed + Sorafenib n=4 Participants Pemetrexed 375mg/m2 intravenously (IV) Day 1 + Sorafenib 200mg by mouth twice daily on days 1-5, every 21 days of each cycle. Experimental Arm B: Pemetrexed: Treatment schedule is administered on day 1 of each 21-day cycle by Intravenous infusion over 10 minutes with a dose of 375 mg/m2. If necessary, the duration of the pemetrexed infusion may be extended to a maximum of 20 minutes. Experimental Arm B: Sorafenib: Treatment schedule is administered twice daily by mouth on an empty stomach on days 1-5 of each 21-day cycle with a dose of 200 mg.
The Percentage of Patients With Objective Response Either Partial Response (PR) or Complete Response(CR). Partial Response	2 Participants	1 Participants
The Percentage of Patients With Objective Response Either Partial Response (PR) or Complete Response(CR). Stable Disease	1 Participants	1 Participants
The Percentage of Patients With Objective Response Either Partial Response (PR) or Complete Response(CR). Progressive Disease	5 Participants	0 Participants
The Percentage of Patients With Objective Response Either Partial Response (PR) or Complete Response(CR). Not Evaluable for Response	1 Participants	2 Participants

SECONDARY outcome

Timeframe: 2 years 3 months

Progression-free survival (PFS) defined as the time (in days) from initiation of study treatment until documented disease progression or death, whichever occurs first.

Outcome measures

Outcome measures
Measure	A: Pemetrexed + Sorafenib n=9 Participants Pemetrexed 500 mg/m2 IV Day 1 + Sorafenib 400mg PO twice each day on Days 1-5 of each 14-day cycle Experimental Arm A: Pemetrexed: Treatment schedule is administered on day 1 of each 14-day cycle by Intravenous infusion over 10 minutes with a dose of 500 mg/m2. If necessary, the duration of the pemetrexed infusion may be extended to a maximum of 20 minutes. Experimental Arm A: Sorafenib: Treatment schedule is administered twice daily by mouth on an empty stomach on days 1-5 of each 14-day cycle with a dose of 400 mg.	B: Pemetrexed + Sorafenib n=4 Participants Pemetrexed 375mg/m2 intravenously (IV) Day 1 + Sorafenib 200mg by mouth twice daily on days 1-5, every 21 days of each cycle. Experimental Arm B: Pemetrexed: Treatment schedule is administered on day 1 of each 21-day cycle by Intravenous infusion over 10 minutes with a dose of 375 mg/m2. If necessary, the duration of the pemetrexed infusion may be extended to a maximum of 20 minutes. Experimental Arm B: Sorafenib: Treatment schedule is administered twice daily by mouth on an empty stomach on days 1-5 of each 21-day cycle with a dose of 200 mg.
The Duration of Progression-free Survival (PFS). Participant A	141 Days	NA Days Participant A participated in Arm A only.
The Duration of Progression-free Survival (PFS). Participant B	60 Days	NA Days Participant B participated in Arm A only.
The Duration of Progression-free Survival (PFS). Participant C	28 Days	NA Days Participant C participated in Arm A only.
The Duration of Progression-free Survival (PFS). Participant D	120 Days	NA Days Participant D participated in Arm A only.
The Duration of Progression-free Survival (PFS). Participant E	259 Days	NA Days Participant E participated in Arm A only.
The Duration of Progression-free Survival (PFS). Participant F	59 Days	NA Days Participant F participated in Arm A only.
The Duration of Progression-free Survival (PFS). Participant G	64 Days	NA Days Participant G participated in Arm A only.
The Duration of Progression-free Survival (PFS). Participant H	49 Days	NA Days Participant H participated in Arm A only.
The Duration of Progression-free Survival (PFS). Participant I	56 Days	NA Days Participant I participated in Arm A only.
The Duration of Progression-free Survival (PFS). Participant J	NA Days Participant J participated in Arm B only.	22 Days
The Duration of Progression-free Survival (PFS). Participant K	NA Days Participant K participated in Arm B only.	100 Days
The Duration of Progression-free Survival (PFS). Participant L	NA Days Participant L participated in Arm B only.	160 Days
The Duration of Progression-free Survival (PFS). Participant M	NA Days Participant M participated in Arm B only.	19 Days

SECONDARY outcome

Timeframe: 2 years 3 months

The proportion of patients who are alive at 2 years following initiation of study treatment.

Outcome measures

Outcome measures
Measure	A: Pemetrexed + Sorafenib n=9 Participants Pemetrexed 500 mg/m2 IV Day 1 + Sorafenib 400mg PO twice each day on Days 1-5 of each 14-day cycle Experimental Arm A: Pemetrexed: Treatment schedule is administered on day 1 of each 14-day cycle by Intravenous infusion over 10 minutes with a dose of 500 mg/m2. If necessary, the duration of the pemetrexed infusion may be extended to a maximum of 20 minutes. Experimental Arm A: Sorafenib: Treatment schedule is administered twice daily by mouth on an empty stomach on days 1-5 of each 14-day cycle with a dose of 400 mg.	B: Pemetrexed + Sorafenib n=4 Participants Pemetrexed 375mg/m2 intravenously (IV) Day 1 + Sorafenib 200mg by mouth twice daily on days 1-5, every 21 days of each cycle. Experimental Arm B: Pemetrexed: Treatment schedule is administered on day 1 of each 21-day cycle by Intravenous infusion over 10 minutes with a dose of 375 mg/m2. If necessary, the duration of the pemetrexed infusion may be extended to a maximum of 20 minutes. Experimental Arm B: Sorafenib: Treatment schedule is administered twice daily by mouth on an empty stomach on days 1-5 of each 21-day cycle with a dose of 200 mg.
The 2-year Survival Rate After Initial Study Treatment.	1 Participants	0 Participants

SECONDARY outcome

Timeframe: 2 years 3 months

To further characterize the safety and side effect profile of the combination. All participants' AEs will be listed and summary descriptive statistics will be calculated.The Adverse events (AEs) are reported using criteria in the National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0).

Outcome measures

Outcome measures
Measure	A: Pemetrexed + Sorafenib n=9 Participants Pemetrexed 500 mg/m2 IV Day 1 + Sorafenib 400mg PO twice each day on Days 1-5 of each 14-day cycle Experimental Arm A: Pemetrexed: Treatment schedule is administered on day 1 of each 14-day cycle by Intravenous infusion over 10 minutes with a dose of 500 mg/m2. If necessary, the duration of the pemetrexed infusion may be extended to a maximum of 20 minutes. Experimental Arm A: Sorafenib: Treatment schedule is administered twice daily by mouth on an empty stomach on days 1-5 of each 14-day cycle with a dose of 400 mg.	B: Pemetrexed + Sorafenib n=4 Participants Pemetrexed 375mg/m2 intravenously (IV) Day 1 + Sorafenib 200mg by mouth twice daily on days 1-5, every 21 days of each cycle. Experimental Arm B: Pemetrexed: Treatment schedule is administered on day 1 of each 21-day cycle by Intravenous infusion over 10 minutes with a dose of 375 mg/m2. If necessary, the duration of the pemetrexed infusion may be extended to a maximum of 20 minutes. Experimental Arm B: Sorafenib: Treatment schedule is administered twice daily by mouth on an empty stomach on days 1-5 of each 21-day cycle with a dose of 200 mg.
Number of Participants at Risk and Affected by Adverse Events (AEs) At Risk	9 Participants	4 Participants
Number of Participants at Risk and Affected by Adverse Events (AEs) Affected	9 Participants	4 Participants

Adverse Events

A: Pemetrexed + Sorafenib

Serious events: 5 serious events

Other events: 9 other events

Deaths: 1 deaths

B: Pemetrexed + Sorafenib

Serious events: 3 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Andrew Poklepovic, MD

Virginia Commonwealth University Massey Cancer Center

Phone: (804) 828-0450

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	A: Pemetrexed + Sorafenib n=9 participants at risk Pemetrexed 500 mg/m2 IV Day 1 + Sorafenib 400mg PO twice each day on Days 1-5 of each 14-day cycle Experimental Arm A: Pemetrexed: Treatment schedule is administered on day 1 of each 14-day cycle by Intravenous infusion over 10 minutes with a dose of 500 mg/m2. If necessary, the duration of the pemetrexed infusion may be extended to a maximum of 20 minutes. Experimental Arm A: Sorafenib: Treatment schedule is administered twice daily by mouth on an empty stomach on days 1-5 of each 14-day cycle with a dose of 400 mg.	B: Pemetrexed + Sorafenib n=4 participants at risk Pemetrexed 375mg/m2 intravenously (IV) Day 1 + Sorafenib 200mg by mouth twice daily on days 1-5, every 21 days of each cycle. Experimental Arm B: Pemetrexed: Treatment schedule is administered on day 1 of each 21-day cycle by Intravenous infusion over 10 minutes with a dose of 375 mg/m2. If necessary, the duration of the pemetrexed infusion may be extended to a maximum of 20 minutes. Experimental Arm B: Sorafenib: Treatment schedule is administered twice daily by mouth on an empty stomach on days 1-5 of each 21-day cycle with a dose of 200 mg.
Blood and lymphatic system disorders Anemia	11.1% 1/9 • Number of events 2 • Adverse event data were collected over three years, four months.	0.00% 0/4 • Adverse event data were collected over three years, four months.
Cardiac disorders Sinus Tachycardia	11.1% 1/9 • Number of events 1 • Adverse event data were collected over three years, four months.	0.00% 0/4 • Adverse event data were collected over three years, four months.
Gastrointestinal disorders Abdominal Pain	11.1% 1/9 • Number of events 1 • Adverse event data were collected over three years, four months.	50.0% 2/4 • Number of events 2 • Adverse event data were collected over three years, four months.
Gastrointestinal disorders Constipation	11.1% 1/9 • Number of events 1 • Adverse event data were collected over three years, four months.	0.00% 0/4 • Adverse event data were collected over three years, four months.
Gastrointestinal disorders Diarrhea	11.1% 1/9 • Number of events 1 • Adverse event data were collected over three years, four months.	0.00% 0/4 • Adverse event data were collected over three years, four months.
Gastrointestinal disorders Gastrointestinal Disorders- Other, Specify	11.1% 1/9 • Number of events 1 • Adverse event data were collected over three years, four months.	0.00% 0/4 • Adverse event data were collected over three years, four months.
Gastrointestinal disorders Nausea	11.1% 1/9 • Number of events 2 • Adverse event data were collected over three years, four months.	25.0% 1/4 • Number of events 1 • Adverse event data were collected over three years, four months.
Gastrointestinal disorders Vomiting	11.1% 1/9 • Number of events 1 • Adverse event data were collected over three years, four months.	25.0% 1/4 • Number of events 1 • Adverse event data were collected over three years, four months.
General disorders Fatigue	22.2% 2/9 • Number of events 2 • Adverse event data were collected over three years, four months.	0.00% 0/4 • Adverse event data were collected over three years, four months.
General disorders Fever	22.2% 2/9 • Number of events 2 • Adverse event data were collected over three years, four months.	0.00% 0/4 • Adverse event data were collected over three years, four months.
General disorders Malaise	11.1% 1/9 • Number of events 1 • Adverse event data were collected over three years, four months.	0.00% 0/4 • Adverse event data were collected over three years, four months.
Hepatobiliary disorders Gallbladder Obstruction	0.00% 0/9 • Adverse event data were collected over three years, four months.	25.0% 1/4 • Number of events 1 • Adverse event data were collected over three years, four months.
Infections and infestations Kidney Infection	11.1% 1/9 • Number of events 1 • Adverse event data were collected over three years, four months.	0.00% 0/4 • Adverse event data were collected over three years, four months.
Infections and infestations Urinary Tract infection	11.1% 1/9 • Number of events 1 • Adverse event data were collected over three years, four months.	0.00% 0/4 • Adverse event data were collected over three years, four months.
Investigations Alanine aminotransferase increased	0.00% 0/9 • Adverse event data were collected over three years, four months.	50.0% 2/4 • Number of events 2 • Adverse event data were collected over three years, four months.
Investigations Aspartate aminotransferase increased	0.00% 0/9 • Adverse event data were collected over three years, four months.	50.0% 2/4 • Number of events 2 • Adverse event data were collected over three years, four months.
Investigations Blood bilirubin increased	11.1% 1/9 • Number of events 1 • Adverse event data were collected over three years, four months.	50.0% 2/4 • Number of events 3 • Adverse event data were collected over three years, four months.
Investigations Investigations - Other, specify	0.00% 0/9 • Adverse event data were collected over three years, four months.	25.0% 1/4 • Number of events 1 • Adverse event data were collected over three years, four months.
Investigations Lymphocyte count decreased	11.1% 1/9 • Number of events 1 • Adverse event data were collected over three years, four months.	0.00% 0/4 • Adverse event data were collected over three years, four months.
Investigations Platelet count decreased	11.1% 1/9 • Number of events 2 • Adverse event data were collected over three years, four months.	0.00% 0/4 • Adverse event data were collected over three years, four months.
Metabolism and nutrition disorders Acidosis	11.1% 1/9 • Number of events 1 • Adverse event data were collected over three years, four months.	0.00% 0/4 • Adverse event data were collected over three years, four months.
Metabolism and nutrition disorders Dehydration	22.2% 2/9 • Number of events 3 • Adverse event data were collected over three years, four months.	0.00% 0/4 • Adverse event data were collected over three years, four months.
Metabolism and nutrition disorders Hypoalbuminemia	11.1% 1/9 • Number of events 1 • Adverse event data were collected over three years, four months.	0.00% 0/4 • Adverse event data were collected over three years, four months.
Musculoskeletal and connective tissue disorders Flank Pain	11.1% 1/9 • Number of events 1 • Adverse event data were collected over three years, four months.	0.00% 0/4 • Adverse event data were collected over three years, four months.
Musculoskeletal and connective tissue disorders Generalized muscle weakness	11.1% 1/9 • Number of events 1 • Adverse event data were collected over three years, four months.	0.00% 0/4 • Adverse event data were collected over three years, four months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	11.1% 1/9 • Number of events 1 • Adverse event data were collected over three years, four months.	0.00% 0/4 • Adverse event data were collected over three years, four months.
Nervous system disorders Depressed level of consciousness	11.1% 1/9 • Number of events 1 • Adverse event data were collected over three years, four months.	0.00% 0/4 • Adverse event data were collected over three years, four months.
Psychiatric disorders Confusion	11.1% 1/9 • Number of events 1 • Adverse event data were collected over three years, four months.	0.00% 0/4 • Adverse event data were collected over three years, four months.
Psychiatric disorders Delirium	0.00% 0/9 • Adverse event data were collected over three years, four months.	25.0% 1/4 • Number of events 2 • Adverse event data were collected over three years, four months.
Respiratory, thoracic and mediastinal disorders Dyspnea	22.2% 2/9 • Number of events 2 • Adverse event data were collected over three years, four months.	0.00% 0/4 • Adverse event data were collected over three years, four months.
Respiratory, thoracic and mediastinal disorders Hypoxia	11.1% 1/9 • Number of events 1 • Adverse event data were collected over three years, four months.	0.00% 0/4 • Adverse event data were collected over three years, four months.
Respiratory, thoracic and mediastinal disorders Respiratory failure	22.2% 2/9 • Number of events 2 • Adverse event data were collected over three years, four months.	0.00% 0/4 • Adverse event data were collected over three years, four months.
Vascular disorders Hypotension	11.1% 1/9 • Number of events 1 • Adverse event data were collected over three years, four months.	0.00% 0/4 • Adverse event data were collected over three years, four months.
Vascular disorders Thromboembolic event	11.1% 1/9 • Number of events 1 • Adverse event data were collected over three years, four months.	0.00% 0/4 • Adverse event data were collected over three years, four months.