Trial Outcomes & Findings for Vinorelbine With Trastuzumab Emtansine in Pre-Treated HER2-Positive Metastatic Breast Cancer (NCT NCT02658084)
NCT ID: NCT02658084
Last Updated: 2019-04-17
Results Overview
Identifying the Maximum Tolerated Dose (MTD) of Vinorelbine combined with a fixed dose of Trastuzumab Emtansine to be recommended for the phase II portion of the study (RP2D).
Recruitment status
TERMINATED
Study phase
PHASE1/PHASE2
Target enrollment
2 participants
Primary outcome timeframe
2 years
Results posted on
2019-04-17
Participant Flow
Participant milestones
| Measure |
Phase 1: T-DM1 + Vinorelbine
One cycle of Trastuzumab Emtansine (T-DM1)/Vinorelbine combination treatment is defined as 21-days (i.e. 3 weeks). The recommended (starting) dose of trastuzumab emtansine is 3.6 mg/kg given as an intravenous infusion on Day 1 of every 21-day cycle. The starting dose of Vinorelbine is 22.5 mg/m2 given as a direct intravenous push over 6-10 minutes on day 1 and day 8 of every 3-week (i.e. 21-day) cycle. Participants will be treated until documented disease progression or other criteria for discontinuation. Approximately 15 to 21 patients will be needed to establish the recommended phase II dose (RP2D).
Vinorelbine: Administered as an intravenous infusion on Day 1 and Day 8 of every 21-day cycle.
Trastuzumab Emtansine: Administered as an intravenous infusion on Day 1 of every 21-day cycle.
|
Phase 2: T-DM1 + RP2D Vinorelbine
One cycle of trastuzumab emtansine (T-DM1)/vinorelbine combination treatment is defined as 21-days (i.e. 3 weeks). Participants will receive the recommended Phase 2 Dose (RPSD) of Vinorelbine with the fixed dose (3.6 mg/kg) of Trastuzumab Emtansine. Participants will be treated until documented disease progression or other criteria for discontinuation. Up to 35 patients will be treated at the RP2D (MTD) including 6 patients treated at RP2D in phase I.
Vinorelbine: Administered as an intravenous infusion on Day 1 and Day 8 of every 21-day cycle.
Trastuzumab Emtansine: Administered as an intravenous infusion on Day 1 of every 21-day cycle.
|
|---|---|---|
|
Overall Study
STARTED
|
2
|
0
|
|
Overall Study
COMPLETED
|
0
|
0
|
|
Overall Study
NOT COMPLETED
|
2
|
0
|
Reasons for withdrawal
| Measure |
Phase 1: T-DM1 + Vinorelbine
One cycle of Trastuzumab Emtansine (T-DM1)/Vinorelbine combination treatment is defined as 21-days (i.e. 3 weeks). The recommended (starting) dose of trastuzumab emtansine is 3.6 mg/kg given as an intravenous infusion on Day 1 of every 21-day cycle. The starting dose of Vinorelbine is 22.5 mg/m2 given as a direct intravenous push over 6-10 minutes on day 1 and day 8 of every 3-week (i.e. 21-day) cycle. Participants will be treated until documented disease progression or other criteria for discontinuation. Approximately 15 to 21 patients will be needed to establish the recommended phase II dose (RP2D).
Vinorelbine: Administered as an intravenous infusion on Day 1 and Day 8 of every 21-day cycle.
Trastuzumab Emtansine: Administered as an intravenous infusion on Day 1 of every 21-day cycle.
|
Phase 2: T-DM1 + RP2D Vinorelbine
One cycle of trastuzumab emtansine (T-DM1)/vinorelbine combination treatment is defined as 21-days (i.e. 3 weeks). Participants will receive the recommended Phase 2 Dose (RPSD) of Vinorelbine with the fixed dose (3.6 mg/kg) of Trastuzumab Emtansine. Participants will be treated until documented disease progression or other criteria for discontinuation. Up to 35 patients will be treated at the RP2D (MTD) including 6 patients treated at RP2D in phase I.
Vinorelbine: Administered as an intravenous infusion on Day 1 and Day 8 of every 21-day cycle.
Trastuzumab Emtansine: Administered as an intravenous infusion on Day 1 of every 21-day cycle.
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
|
Overall Study
Study Termination
|
1
|
0
|
Baseline Characteristics
Vinorelbine With Trastuzumab Emtansine in Pre-Treated HER2-Positive Metastatic Breast Cancer
Baseline characteristics by cohort
| Measure |
Phase 1: T-DM1 + Vinorelbine
n=2 Participants
One cycle of Trastuzumab Emtansine (T-DM1)/Vinorelbine combination treatment is defined as 21-days (i.e. 3 weeks). The recommended (starting) dose of trastuzumab emtansine is 3.6 mg/kg given as an intravenous infusion on Day 1 of every 21-day cycle. The starting dose of Vinorelbine is 22.5 mg/m2 given as a direct intravenous push over 6-10 minutes on day 1 and day 8 of every 3-week (i.e. 21-day) cycle. Participants will be treated until documented disease progression or other criteria for discontinuation. Approximately 15 to 21 patients will be needed to establish the recommended phase II dose (RP2D).
Vinorelbine: Administered as an intravenous infusion on Day 1 and Day 8 of every 21-day cycle.
Trastuzumab Emtansine: Administered as an intravenous infusion on Day 1 of every 21-day cycle.
|
Phase 2: T-DM1 + RP2D Vinorelbine
One cycle of trastuzumab emtansine (T-DM1)/vinorelbine combination treatment is defined as 21-days (i.e. 3 weeks). Participants will receive the recommended Phase 2 Dose (RPSD) of Vinorelbine with the fixed dose (3.6 mg/kg) of Trastuzumab Emtansine. Participants will be treated until documented disease progression or other criteria for discontinuation. Up to 35 patients will be treated at the RP2D (MTD) including 6 patients treated at RP2D in phase I.
Vinorelbine: Administered as an intravenous infusion on Day 1 and Day 8 of every 21-day cycle.
Trastuzumab Emtansine: Administered as an intravenous infusion on Day 1 of every 21-day cycle.
|
Total
n=2 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
2 participants
n=5 Participants
|
—
|
2 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 2 yearsPopulation: Approximately 15 to 21 participants would be needed to establish the recommended phase II dose (RP2D). Only 2 participants were enrolled therefore the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) were not determined.
Identifying the Maximum Tolerated Dose (MTD) of Vinorelbine combined with a fixed dose of Trastuzumab Emtansine to be recommended for the phase II portion of the study (RP2D).
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Up to 5 yearsPopulation: The Phase 2 arm did not open to accrual. No participants were enrolled to Phase 2.
Rate of Progression-Free Survival (PFS) in participants receiving the RP2D of vinorelbine in combination with Trastuzumab Emtansine therapy. PFS is defined as the time from date from first treatment received on study until documented disease progression or death (by any cause, in the absence of progression). In progression-free patients, PFS will be censored at the last evaluable tumor assessment according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: 18 monthsPopulation: For adverse events, participants who received at least one dose of study therapy. For dose-limiting toxicities, participants who experienced a dose-limiting toxicity during the first two cycles of study therapy.
Rate of participants experiencing adverse events including dose-limiting toxicities (DLTs) and serious adverse events (SAEs).
Outcome measures
| Measure |
Phase 1: T-DM1 + Vinorelbine
n=2 Participants
One cycle of Trastuzumab Emtansine (T-DM1)/Vinorelbine combination treatment is defined as 21-days (i.e. 3 weeks). The recommended (starting) dose of trastuzumab emtansine is 3.6 mg/kg given as an intravenous infusion on Day 1 of every 21-day cycle. The starting dose of Vinorelbine is 22.5 mg/m2 given as a direct intravenous push over 6-10 minutes on day 1 and day 8 of every 3-week (i.e. 21-day) cycle. Participants will be treated until documented disease progression or other criteria for discontinuation. Approximately 15 to 21 patients will be needed to establish the recommended phase II dose (RP2D).
Vinorelbine: Administered as an intravenous infusion on Day 1 and Day 8 of every 21-day cycle.
Trastuzumab Emtansine: Administered as an intravenous infusion on Day 1 of every 21-day cycle.
|
|---|---|
|
Phase 1 - Rate of Participants Experiencing Adverse Events
Dose-limiting toxicities (DLTs)
|
2 participants
|
|
Phase 1 - Rate of Participants Experiencing Adverse Events
Adverse events (AEs)
|
2 participants
|
SECONDARY outcome
Timeframe: Up to 5 yearsPopulation: The Phase 2 arm did not open to accrual. No participants were enrolled to Phase 2.
Rate of participants achieving best overall response of complete response (CR), partial response (PR) or stable disease (SD) for \>/= 6 months on protocol therapy, according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to 5 YearsPopulation: The Phase 2 arm did not open to accrual. No participants were enrolled to Phase 2.
Overall Survival (OS) is defined as the elapsed time from date from first treatment received on study to death or date of censoring. Patients alive or those lost to follow-up will be censored at the last date of contact (or last date known to be alive).
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to 5 YearsPopulation: The Phase 2 arm did not open to accrual. No participants were enrolled to Phase 2.
Rate of participants achieving a best overall response of complete response (CR) or partial response (PR) to protocol therapy according to Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1 criteria.
Outcome measures
Outcome data not reported
Adverse Events
Phase 1: T-DM1 + Vinorelbine
Serious events: 2 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Phase 1: T-DM1 + Vinorelbine
n=2 participants at risk
One cycle of Trastuzumab Emtansine (T-DM1)/Vinorelbine combination treatment is defined as 21-days (i.e. 3 weeks). The recommended (starting) dose of trastuzumab emtansine is 3.6 mg/kg given as an intravenous infusion on Day 1 of every 21-day cycle. The starting dose of Vinorelbine is 22.5 mg/m2 given as a direct intravenous push over 6-10 minutes on day 1 and day 8 of every 3-week (i.e. 21-day) cycle. Participants will be treated until documented disease progression or other criteria for discontinuation. Approximately 15 to 21 patients will be needed to establish the recommended phase II dose (RP2D).
Vinorelbine: Administered as an intravenous infusion on Day 1 and Day 8 of every 21-day cycle.
Trastuzumab Emtansine: Administered as an intravenous infusion on Day 1 of every 21-day cycle.
|
|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
100.0%
2/2 • Number of events 2 • 18 months
|
|
Metabolism and nutrition disorders
Anorexia
|
50.0%
1/2 • Number of events 1 • 18 months
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
50.0%
1/2 • Number of events 1 • 18 months
|
|
Cardiac disorders
Chest pain - cardiac
|
50.0%
1/2 • Number of events 1 • 18 months
|
|
Gastrointestinal disorders
Constipation
|
50.0%
1/2 • Number of events 1 • 18 months
|
|
Gastrointestinal disorders
Dyspepsia
|
50.0%
1/2 • Number of events 1 • 18 months
|
|
General disorders
Fatigue
|
100.0%
2/2 • Number of events 2 • 18 months
|
|
Gastrointestinal disorders
Gastroparesis
|
50.0%
1/2 • Number of events 1 • 18 months
|
|
Metabolism and nutrition disorders
Hypokalemia
|
50.0%
1/2 • Number of events 1 • 18 months
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
50.0%
1/2 • Number of events 1 • 18 months
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
50.0%
1/2 • Number of events 1 • 18 months
|
|
Gastrointestinal disorders
Nausea
|
50.0%
1/2 • Number of events 1 • 18 months
|
|
General disorders
Pain
|
50.0%
1/2 • Number of events 1 • 18 months
|
|
Gastrointestinal disorders
Vomiting
|
50.0%
1/2 • Number of events 1 • 18 months
|
Other adverse events
| Measure |
Phase 1: T-DM1 + Vinorelbine
n=2 participants at risk
One cycle of Trastuzumab Emtansine (T-DM1)/Vinorelbine combination treatment is defined as 21-days (i.e. 3 weeks). The recommended (starting) dose of trastuzumab emtansine is 3.6 mg/kg given as an intravenous infusion on Day 1 of every 21-day cycle. The starting dose of Vinorelbine is 22.5 mg/m2 given as a direct intravenous push over 6-10 minutes on day 1 and day 8 of every 3-week (i.e. 21-day) cycle. Participants will be treated until documented disease progression or other criteria for discontinuation. Approximately 15 to 21 patients will be needed to establish the recommended phase II dose (RP2D).
Vinorelbine: Administered as an intravenous infusion on Day 1 and Day 8 of every 21-day cycle.
Trastuzumab Emtansine: Administered as an intravenous infusion on Day 1 of every 21-day cycle.
|
|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
50.0%
1/2 • Number of events 1 • 18 months
|
|
Investigations
Alanine aminotransferase increased
|
100.0%
2/2 • Number of events 2 • 18 months
|
|
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis
|
50.0%
1/2 • Number of events 1 • 18 months
|
|
Metabolism and nutrition disorders
Anorexia
|
100.0%
2/2 • Number of events 2 • 18 months
|
|
Psychiatric disorders
Anxiety
|
50.0%
1/2 • Number of events 1 • 18 months
|
|
Metabolism and nutrition disorders
Aspartate aminotransferase increased
|
100.0%
2/2 • Number of events 3 • 18 months
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
50.0%
1/2 • Number of events 1 • 18 months
|
|
Blood and lymphatic system disorders
Hypercapnia
|
50.0%
1/2 • Number of events 1 • 18 months
|
|
General disorders
Chills
|
50.0%
1/2 • Number of events 1 • 18 months
|
|
Gastrointestinal disorders
Constipation
|
50.0%
1/2 • Number of events 1 • 18 months
|
|
Metabolism and nutrition disorders
Dehydration
|
50.0%
1/2 • Number of events 1 • 18 months
|
|
Gastrointestinal disorders
Diarrhea
|
50.0%
1/2 • Number of events 1 • 18 months
|
|
Nervous system disorders
Dizziness
|
50.0%
1/2 • Number of events 1 • 18 months
|
|
Gastrointestinal disorders
Dyspepsia
|
50.0%
1/2 • Number of events 1 • 18 months
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
50.0%
1/2 • Number of events 1 • 18 months
|
|
General disorders
Fatigue
|
100.0%
2/2 • Number of events 6 • 18 months
|
|
General disorders
Fever
|
50.0%
1/2 • Number of events 1 • 18 months
|
|
General disorders
Flu like symptoms
|
50.0%
1/2 • Number of events 1 • 18 months
|
|
Vascular disorders
Hypertension
|
50.0%
1/2 • Number of events 1 • 18 months
|
|
Metabolism and nutrition disorders
Hypokalemia
|
50.0%
1/2 • Number of events 1 • 18 months
|
|
Nervous system disorders
Lethargy
|
50.0%
1/2 • Number of events 1 • 18 months
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
50.0%
1/2 • Number of events 1 • 18 months
|
|
Gastrointestinal disorders
Nausea
|
100.0%
2/2 • Number of events 2 • 18 months
|
|
Investigations
Platelet count decreased
|
100.0%
2/2 • Number of events 3 • 18 months
|
|
Nervous system disorders
Somnolence
|
50.0%
1/2 • Number of events 1 • 18 months
|
|
Gastrointestinal disorders
Stomach pain
|
50.0%
1/2 • Number of events 1 • 18 months
|
|
Gastrointestinal disorders
Vomiting
|
50.0%
1/2 • Number of events 1 • 18 months
|
|
Blood and lymphatic system disorders
Hypochloremia
|
50.0%
1/2 • Number of events 1 • 18 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place