Trial Outcomes & Findings for Nab-Paclitaxel and Bevacizumab Followed By Bevacizumab and Erlotinib in Metastatic Breast Cancer (NCT NCT00733408)

Last Updated: 2018-12-04

Results Overview

Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions. Kaplan-Meier survival curves will be used. A 95% confidence interval for the median PFS will be calculated. A lower bound greater than 8 months would be strong evidence that Nab-Paclitaxel- bevacizumab induction therapy followed by bevacizumab-erlotinib hydrochloride maintenance therapy is superior to paclitaxel and bevacizumab. However, a median PFS of 13 months or greater (regardless of whether the 95% confidence interval for the median extends below 8 months) could also indicate promising results.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

59 participants

Primary outcome timeframe

Time from date of registration to date of first documentation of progression or symptomatic deterioration or death due to any cause, assessed up to 8 years

Results posted on

2018-12-04

Participant Flow

Participant milestones

Participant milestones
Measure	Tx (Chemo, MoAb, and Enzyme Inhibitor) INDUCTION THERAPY: Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV on days 1, 8, and 15 and bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients achieving complete response, partial response, or stable disease after completion of induction therapy will receive bevacizumab IV over 30-90 minutes once every 14 or 21 days and erlotinib hydrochloride PO QD in the absence of disease progression or unacceptable toxicity. paclitaxel albumin-stabilized nanoparticle formulation: Given IV bevacizumab: Given IV erlotinib hydrochloride: Given PO
Overall Study STARTED	59
Overall Study COMPLETED	55
Overall Study NOT COMPLETED	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Tx (Chemo, MoAb, and Enzyme Inhibitor) INDUCTION THERAPY: Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV on days 1, 8, and 15 and bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients achieving complete response, partial response, or stable disease after completion of induction therapy will receive bevacizumab IV over 30-90 minutes once every 14 or 21 days and erlotinib hydrochloride PO QD in the absence of disease progression or unacceptable toxicity. paclitaxel albumin-stabilized nanoparticle formulation: Given IV bevacizumab: Given IV erlotinib hydrochloride: Given PO
Overall Study Adverse Event	4

Baseline Characteristics

Nab-Paclitaxel and Bevacizumab Followed By Bevacizumab and Erlotinib in Metastatic Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tx (Chemo, MoAb, and Enzyme Inhibitor) n=55 Participants INDUCTION THERAPY: Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV on days 1, 8, and 15 and bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients achieving complete response, partial response, or stable disease after completion of induction therapy will receive bevacizumab IV over 30-90 minutes once every 14 or 21 days and erlotinib hydrochloride PO QD in the absence of disease progression or unacceptable toxicity. paclitaxel albumin-stabilized nanoparticle formulation: Given IV bevacizumab: Given IV erlotinib hydrochloride: Given PO
Age, Continuous	55.3 years STANDARD_DEVIATION 12.5 • n=5 Participants
Sex: Female, Male Female	55 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	47 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants
Race (NIH/OMB) White	47 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: Time from date of registration to date of first documentation of progression or symptomatic deterioration or death due to any cause, assessed up to 8 years

Outcome measures

Outcome measures
Measure	Tx (Chemo, MoAb, and Enzyme Inhibitor) n=55 Participants INDUCTION THERAPY: Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV on days 1, 8, and 15 and bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients achieving complete response, partial response, or stable disease after completion of induction therapy will receive bevacizumab IV over 30-90 minutes once every 14 or 21 days and erlotinib hydrochloride PO QD in the absence of disease progression or unacceptable toxicity. paclitaxel albumin-stabilized nanoparticle formulation: Given IV bevacizumab: Given IV erlotinib hydrochloride: Given PO
Progression-free Survival (PFS)	9.1 Months Interval 7.2 to 11.1

SECONDARY outcome

Timeframe: Time from date of registration to date of death due to any cause, assessed up to 8 years

Kaplan-Meier survival curves will be used.

Outcome measures

Outcome measures
Measure	Tx (Chemo, MoAb, and Enzyme Inhibitor) n=55 Participants INDUCTION THERAPY: Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV on days 1, 8, and 15 and bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients achieving complete response, partial response, or stable disease after completion of induction therapy will receive bevacizumab IV over 30-90 minutes once every 14 or 21 days and erlotinib hydrochloride PO QD in the absence of disease progression or unacceptable toxicity. paclitaxel albumin-stabilized nanoparticle formulation: Given IV bevacizumab: Given IV erlotinib hydrochloride: Given PO
Overall Survival	18.1 Months Interval 15.6 to 21.7

SECONDARY outcome

Timeframe: Up to 8 years

Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.

Outcome measures

Outcome measures
Measure	Tx (Chemo, MoAb, and Enzyme Inhibitor) n=53 Participants INDUCTION THERAPY: Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV on days 1, 8, and 15 and bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients achieving complete response, partial response, or stable disease after completion of induction therapy will receive bevacizumab IV over 30-90 minutes once every 14 or 21 days and erlotinib hydrochloride PO QD in the absence of disease progression or unacceptable toxicity. paclitaxel albumin-stabilized nanoparticle formulation: Given IV bevacizumab: Given IV erlotinib hydrochloride: Given PO
Percentage of Participants With Response Stable Disease	19 percentage of participants Interval 11.0 to 30.0
Percentage of Participants With Response Partial Response	74 percentage of participants Interval 62.0 to 83.0

SECONDARY outcome

Timeframe: Up to 30 days after treatment discontinuation

Population: Of the 59 patients enrolled, 4 patients failed to complete a single cycle of induction and considered invaluable and therefore were removed from efficacy analysis. Safety analysis included all 59 patients.

Adverse events that meet severity grade 2 or greater will be collected and reported. The number and percent of subjects reporting adverse events (all, severe or worse, serious and related) will be summarized for all patients, and stratified by center and other subgroups of interest.

Outcome measures

Outcome measures
Measure	Tx (Chemo, MoAb, and Enzyme Inhibitor) n=59 Participants INDUCTION THERAPY: Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV on days 1, 8, and 15 and bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients achieving complete response, partial response, or stable disease after completion of induction therapy will receive bevacizumab IV over 30-90 minutes once every 14 or 21 days and erlotinib hydrochloride PO QD in the absence of disease progression or unacceptable toxicity. paclitaxel albumin-stabilized nanoparticle formulation: Given IV bevacizumab: Given IV erlotinib hydrochloride: Given PO
Incidence of Adverse Events as Assessed by National Cancer Institute CTCAE Version 3.0 Grade 3, 4 Toxicities for Induction	34 Participants
Incidence of Adverse Events as Assessed by National Cancer Institute CTCAE Version 3.0 Grade 3, 4 Toxicities for Maintenance	14 Participants

SECONDARY outcome

Timeframe: Up to 8 years

Population: Data published that shows that running assay does not provide useful results

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to up to 8 years

Descriptive statistics, such as mean, standard deviation, and range, will be summarized for circulating tumor cells at baseline and last visit.

Outcome measures

Outcome measures
Measure	Tx (Chemo, MoAb, and Enzyme Inhibitor) n=55 Participants INDUCTION THERAPY: Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV on days 1, 8, and 15 and bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients achieving complete response, partial response, or stable disease after completion of induction therapy will receive bevacizumab IV over 30-90 minutes once every 14 or 21 days and erlotinib hydrochloride PO QD in the absence of disease progression or unacceptable toxicity. paclitaxel albumin-stabilized nanoparticle formulation: Given IV bevacizumab: Given IV erlotinib hydrochloride: Given PO
Changes in Levels of Circulating Tumor Cells log10(CTC) at baseline	0.857 log10 of CTC per mL Standard Deviation 0.854
Changes in Levels of Circulating Tumor Cells log10(CTC) at last visit	0.531 log10 of CTC per mL Standard Deviation 0.756

SECONDARY outcome

Timeframe: Baseline to up to 8 years

Descriptive statistics, such as mean and standard deviation, will be summarized for circulating endothelial cells at baseline and last visit.

Outcome measures

Outcome measures
Measure	Tx (Chemo, MoAb, and Enzyme Inhibitor) n=55 Participants INDUCTION THERAPY: Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV on days 1, 8, and 15 and bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients achieving complete response, partial response, or stable disease after completion of induction therapy will receive bevacizumab IV over 30-90 minutes once every 14 or 21 days and erlotinib hydrochloride PO QD in the absence of disease progression or unacceptable toxicity. paclitaxel albumin-stabilized nanoparticle formulation: Given IV bevacizumab: Given IV erlotinib hydrochloride: Given PO
Changes in Levels of Circulating Endothelial Cells log10(CEC) at baseline	1.458 log10 of CEC per mL Standard Deviation 0.491
Changes in Levels of Circulating Endothelial Cells log10(CEC) at last visit	1.332 log10 of CEC per mL Standard Deviation 0.574

Adverse Events

Tx (Chemo, MoAb, and Enzyme Inhibitor)

Serious events: 5 serious events

Other events: 52 other events

Deaths: 3 deaths

Serious adverse events

Serious adverse events
Measure	Tx (Chemo, MoAb, and Enzyme Inhibitor) n=55 participants at risk INDUCTION THERAPY: Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV on days 1, 8, and 15 and bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients achieving complete response, partial response, or stable disease after completion of induction therapy will receive bevacizumab IV over 30-90 minutes once every 14 or 21 days and erlotinib hydrochloride PO QD in the absence of disease progression or unacceptable toxicity. paclitaxel albumin-stabilized nanoparticle formulation: Given IV bevacizumab: Given IV erlotinib hydrochloride: Given PO
Infections and infestations Infection	3.6% 2/55 • Number of events 2 • Patients were evaluated for adverse events at each study visit for the duration of their participation in the study and for 30 days after the discontinuation.
Musculoskeletal and connective tissue disorders Pain	1.8% 1/55 • Number of events 1 • Patients were evaluated for adverse events at each study visit for the duration of their participation in the study and for 30 days after the discontinuation.
Respiratory, thoracic and mediastinal disorders Dyspnea	1.8% 1/55 • Number of events 1 • Patients were evaluated for adverse events at each study visit for the duration of their participation in the study and for 30 days after the discontinuation.
Musculoskeletal and connective tissue disorders Muscle Weakness	1.8% 1/55 • Number of events 1 • Patients were evaluated for adverse events at each study visit for the duration of their participation in the study and for 30 days after the discontinuation.

Other adverse events

Other adverse events
Measure	Tx (Chemo, MoAb, and Enzyme Inhibitor) n=55 participants at risk INDUCTION THERAPY: Patients receive paclitaxel albumin-stabilized nanoparticle formulation IV on days 1, 8, and 15 and bevacizumab IV over 30-90 minutes on days 1 and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients achieving complete response, partial response, or stable disease after completion of induction therapy will receive bevacizumab IV over 30-90 minutes once every 14 or 21 days and erlotinib hydrochloride PO QD in the absence of disease progression or unacceptable toxicity. paclitaxel albumin-stabilized nanoparticle formulation: Given IV bevacizumab: Given IV erlotinib hydrochloride: Given PO
Blood and lymphatic system disorders Neutropenia	29.1% 16/55 • Number of events 19 • Patients were evaluated for adverse events at each study visit for the duration of their participation in the study and for 30 days after the discontinuation.
General disorders Fatigue	25.5% 14/55 • Number of events 15 • Patients were evaluated for adverse events at each study visit for the duration of their participation in the study and for 30 days after the discontinuation.
Nervous system disorders Neuropathy	14.5% 8/55 • Number of events 8 • Patients were evaluated for adverse events at each study visit for the duration of their participation in the study and for 30 days after the discontinuation.
Musculoskeletal and connective tissue disorders Pain	12.7% 7/55 • Number of events 7 • Patients were evaluated for adverse events at each study visit for the duration of their participation in the study and for 30 days after the discontinuation.
Blood and lymphatic system disorders Lymphopenia	14.5% 8/55 • Number of events 10 • Patients were evaluated for adverse events at each study visit for the duration of their participation in the study and for 30 days after the discontinuation.
Skin and subcutaneous tissue disorders Rash	7.3% 4/55 • Number of events 6 • Patients were evaluated for adverse events at each study visit for the duration of their participation in the study and for 30 days after the discontinuation.
Metabolism and nutrition disorders Anorexia	5.5% 3/55 • Number of events 3 • Patients were evaluated for adverse events at each study visit for the duration of their participation in the study and for 30 days after the discontinuation.
Metabolism and nutrition disorders Dehydration	5.5% 3/55 • Number of events 3 • Patients were evaluated for adverse events at each study visit for the duration of their participation in the study and for 30 days after the discontinuation.
Metabolism and nutrition disorders Hyponatremia	5.5% 3/55 • Number of events 3 • Patients were evaluated for adverse events at each study visit for the duration of their participation in the study and for 30 days after the discontinuation.
Infections and infestations Infection	5.5% 3/55 • Number of events 4 • Patients were evaluated for adverse events at each study visit for the duration of their participation in the study and for 30 days after the discontinuation.
Skin and subcutaneous tissue disorders Nail changes	5.5% 3/55 • Number of events 3 • Patients were evaluated for adverse events at each study visit for the duration of their participation in the study and for 30 days after the discontinuation.
Hepatobiliary disorders LFT Abnormality	3.6% 2/55 • Number of events 2 • Patients were evaluated for adverse events at each study visit for the duration of their participation in the study and for 30 days after the discontinuation.
Skin and subcutaneous tissue disorders Dermatology other	3.6% 2/55 • Number of events 2 • Patients were evaluated for adverse events at each study visit for the duration of their participation in the study and for 30 days after the discontinuation.
Gastrointestinal disorders Diarrhea	3.6% 2/55 • Number of events 2 • Patients were evaluated for adverse events at each study visit for the duration of their participation in the study and for 30 days after the discontinuation.
Blood and lymphatic system disorders Anemia	3.6% 2/55 • Number of events 3 • Patients were evaluated for adverse events at each study visit for the duration of their participation in the study and for 30 days after the discontinuation.
Vascular disorders Hypertension	3.6% 2/55 • Number of events 2 • Patients were evaluated for adverse events at each study visit for the duration of their participation in the study and for 30 days after the discontinuation.
Metabolism and nutrition disorders Hypokalemia	3.6% 2/55 • Number of events 2 • Patients were evaluated for adverse events at each study visit for the duration of their participation in the study and for 30 days after the discontinuation.
Musculoskeletal and connective tissue disorders Muscle Weakness	3.6% 2/55 • Number of events 2 • Patients were evaluated for adverse events at each study visit for the duration of their participation in the study and for 30 days after the discontinuation.
Gastrointestinal disorders Nausea	3.6% 2/55 • Number of events 2 • Patients were evaluated for adverse events at each study visit for the duration of their participation in the study and for 30 days after the discontinuation.
General disorders Weight loss	3.6% 2/55 • Number of events 2 • Patients were evaluated for adverse events at each study visit for the duration of their participation in the study and for 30 days after the discontinuation.

Additional Information

Jennifer Specht, MD, Associate Professor

University of Washington

Phone: (206) 606-1000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60