Trial Outcomes & Findings for Randomized Phase II Study of Preoperative Letrozole (Femara) in Combination With Avastin in Hormone Receptor Positive Breast Cancer (NCT NCT00461773)

Last Updated: 2021-03-16

Results Overview

Clinical objective tumor response with 14 weeks of Neoadjuvant Letrozole combined with Bevacizumab was assessed using the following categories: Complete Response (CR): tumor is no longer visible. Partial response (PR): ≥ 50% decrease from baseline in the product of two perpendicular diameters, no new lesions. Progressive disease (PD): ≥ 25% increase of the product of two perpendicular diameters or new lesions. Stable Disease (SD): Neither CR, PR, or PD criteria met. Clinical tumor assessment was performed at baseline and every 2 weeks until week 18 prior to definitive surgery.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

5 participants

Primary outcome timeframe

Up to 18 weeks

Results posted on

2021-03-16

Participant Flow

Participant milestones

Participant milestones
Measure	Bevacizumab brief exposure bevacizumab Bevacizumab: bevacizumab 10 mg/kg IV	Bevacizumab and Letrozole brief exposure bevacizumab and letrozole Letrozole: Letrozole 2.5 mg once orally daily Bevacizumab: bevacizumab 10 mg/kg IV
Overall Study STARTED	3	2
Overall Study COMPLETED	3	2
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Randomized Phase II Study of Preoperative Letrozole (Femara) in Combination With Avastin in Hormone Receptor Positive Breast Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Bevacizumab n=3 Participants brief exposure bevacizumab	Bevacizumab and Letrozole n=2 Participants brief exposure bevacizumab and letrozole	Total n=5 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	2 Participants n=7 Participants	4 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 18 weeks

Population: All patients.

Outcome measures

Outcome measures
Measure	Bevacizumab n=3 Participants brief exposure bevacizumab	Bevacizumab and Letrozole n=2 Participants brief exposure bevacizumab and letrozole
Number of Patients With Objective Tumor Response Complete Response	1 Participants	0 Participants
Number of Patients With Objective Tumor Response Partial Response	2 Participants	1 Participants
Number of Patients With Objective Tumor Response Progressive Disease	0 Participants	0 Participants
Number of Patients With Objective Tumor Response Stable Disease	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Up to 14 weeks

Population: All patients.

To assess breast conservation (actual surgery performed and baseline feasible surgery) of 14 weeks of neoadjuvant letrozole combined with bevacizumab. At baseline and immediately prior to surgery, the investigator will record the extent of the least invasive feasible surgery option at that time point, according to the following categories: 1. Breast conserving surgery is feasible; 2. A mastectomy is needed; 3. Tumor is inoperable, but potentially operable after neoadjuvant treatment. Following surgery, the investigator will record the extent of the actual surgery performed according to the following categories: 1\. Breast conserving surgery performed; 2. Mastectomy performed 3. No surgery performed (reason should be specified).

Outcome measures

Outcome measures
Measure	Bevacizumab n=3 Participants brief exposure bevacizumab	Bevacizumab and Letrozole n=2 Participants brief exposure bevacizumab and letrozole
Breast Conservation Mastectomy Needed at Baseline · Performed at 14 weeks	1 Participants	1 Participants
Breast Conservation Mastectomy Needed at Baseline · Not Performed at 14 weeks	0 Participants	0 Participants
Breast Conservation Breast Conservation Feasible Baseline · Performed at 14 weeks	2 Participants	1 Participants
Breast Conservation Breast Conservation Feasible Baseline · Not Performed at 14 weeks	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 18 weeks

Population: All patients.

To assess radiographic tumor response after 14 weeks of Neoadjuvant Letrozole combined with Bevacizumab, mammogram were performed at baseline and at week 18 prior to definitive surgery. Tumors response was assessed using RECIST criteria RECIST: CR: Tumor is no longer visible PR: ≥ 30% decrease from baseline in the longest diameter, no new lesions PD: ≥ 20% increase in longest diameter recorded or new lesions SD: Neither CR, PR, or PD criteria met

Outcome measures

Outcome measures
Measure	Bevacizumab n=3 Participants brief exposure bevacizumab	Bevacizumab and Letrozole n=2 Participants brief exposure bevacizumab and letrozole
Radiographic Tumor Response CR	0 Participants	0 Participants
Radiographic Tumor Response PR	2 Participants	2 Participants
Radiographic Tumor Response PD	0 Participants	0 Participants
Radiographic Tumor Response SD	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 18 weeks

Population: All patients.

To assess pathologic complete response after 14 Weeks of Neoadjuvant Letrozole combined with Bevacizumab, the pathologic response was determined on the surgically excised specimen at the time of definitive surgery. The size of the residual tumor would be measured grossly if possible and confirmed microscopically. The excised residual tumor was be assessed using RECIST criteria. RECIST: CR: Tumor is no longer visible PR: ≥ 30% decrease from baseline in the longest diameter, no new lesions PD: ≥ 20% increase in longest diameter recorded or new lesions SD: Neither CR, PR, or PD criteria met

Outcome measures

Outcome measures
Measure	Bevacizumab n=3 Participants brief exposure bevacizumab	Bevacizumab and Letrozole n=2 Participants brief exposure bevacizumab and letrozole
Pathologic Complete Response PR	1 Participants	1 Participants
Pathologic Complete Response PD	1 Participants	1 Participants
Pathologic Complete Response SD	1 Participants	0 Participants
Pathologic Complete Response CR	0 Participants	0 Participants

SECONDARY outcome

Timeframe: 2 weeks

Population: These labs were never conducted as the study was terminated after 5 patients.

To correlate response with biological correlates detected at baseline and after 1 cycle of treatment with either Bevacizumab alone or Bevacizumab combined with Letrozole.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 18 weeks

Population: All adverse events are presented in the adverse event module.

To assess the tolerability of 14 weeks of Neoadjuvant Letrozole combined with Bevacizumab, individual toxicities were graded according to the National Cancer Institute (NCI) Common Toxicity Criteria (CTC) Version 3.0. Information about all adverse events, whether volunteered by the subject, discovered by investigator questioning, or detected through physical examination, laboratory test or other means, were collected and recorded on the Adverse Event Case Report Form and followed as appropriate. An adverse event (AE) is any undesirable sign, symptom or medical condition occurring after starting study drug (or therapy) even if the event is not considered to be related to study drug (or therapy). Study drug (or therapy) includes the drug (or therapy) under evaluation, and any reference or placebo drug (or therapy) given during any phase of the trial. AE's graded 3 or 4 would be considered serious and be reported as measures of tolerability.

Outcome measures

Outcome measures
Measure	Bevacizumab n=3 Participants brief exposure bevacizumab	Bevacizumab and Letrozole n=2 Participants brief exposure bevacizumab and letrozole
Drug Tolerability Any Grade 3 Adverse Events	0 Participants	0 Participants
Drug Tolerability Any Grade 4 Adverse Events	0 Participants	0 Participants

Adverse Events

Bevacizumab

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Bevacizumab and Letrozole

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Bevacizumab n=3 participants at risk brief exposure bevacizumab	Bevacizumab and Letrozole n=2 participants at risk brief exposure bevacizumab and letrozole
Immune system disorders ALLERGY/IMMUNOLOGY	66.7% 2/3 • Number of events 4 • Up to 18 weeks	0.00% 0/2 • Up to 18 weeks
Ear and labyrinth disorders AUDITORY/EAR	0.00% 0/3 • Up to 18 weeks	50.0% 1/2 • Number of events 1 • Up to 18 weeks
Blood and lymphatic system disorders BLOOD/BONE MARROW	0.00% 0/3 • Up to 18 weeks	50.0% 1/2 • Number of events 3 • Up to 18 weeks
Cardiac disorders CARDIAC GENERAL	66.7% 2/3 • Number of events 2 • Up to 18 weeks	100.0% 2/2 • Number of events 4 • Up to 18 weeks
General disorders CONSTITUTIONAL SYMPTOMS	66.7% 2/3 • Number of events 10 • Up to 18 weeks	100.0% 2/2 • Number of events 8 • Up to 18 weeks
Skin and subcutaneous tissue disorders DERMATOLOGY/SKIN	66.7% 2/3 • Number of events 9 • Up to 18 weeks	100.0% 2/2 • Number of events 3 • Up to 18 weeks
Endocrine disorders ENDOCRINE	33.3% 1/3 • Number of events 1 • Up to 18 weeks	50.0% 1/2 • Number of events 4 • Up to 18 weeks
Gastrointestinal disorders GASTROINTESTINAL	66.7% 2/3 • Number of events 9 • Up to 18 weeks	100.0% 2/2 • Number of events 8 • Up to 18 weeks
Blood and lymphatic system disorders HEMORRHAGE/BLEEDING	33.3% 1/3 • Number of events 1 • Up to 18 weeks	0.00% 0/2 • Up to 18 weeks
Immune system disorders LYMPHATICS	33.3% 1/3 • Number of events 1 • Up to 18 weeks	0.00% 0/2 • Up to 18 weeks
Metabolism and nutrition disorders METABOLIC/LABORATORY	100.0% 3/3 • Number of events 29 • Up to 18 weeks	100.0% 2/2 • Number of events 20 • Up to 18 weeks
Musculoskeletal and connective tissue disorders MUSCULOSKELETAL/SOFT TISSUE	33.3% 1/3 • Number of events 2 • Up to 18 weeks	50.0% 1/2 • Number of events 1 • Up to 18 weeks
Nervous system disorders NEUROLOGY	33.3% 1/3 • Number of events 1 • Up to 18 weeks	50.0% 1/2 • Number of events 9 • Up to 18 weeks
Eye disorders OCULAR/VISUAL	33.3% 1/3 • Number of events 1 • Up to 18 weeks	100.0% 2/2 • Number of events 2 • Up to 18 weeks
General disorders PAIN	100.0% 3/3 • Number of events 17 • Up to 18 weeks	100.0% 2/2 • Number of events 16 • Up to 18 weeks
Respiratory, thoracic and mediastinal disorders PULMONARY/UPPER RESPIRATORY	33.3% 1/3 • Number of events 2 • Up to 18 weeks	100.0% 2/2 • Number of events 5 • Up to 18 weeks
Renal and urinary disorders RENAL/GENITOURINARY	33.3% 1/3 • Number of events 1 • Up to 18 weeks	0.00% 0/2 • Up to 18 weeks
General disorders SYNDROMES	33.3% 1/3 • Number of events 1 • Up to 18 weeks	0.00% 0/2 • Up to 18 weeks
Vascular disorders VASCULAR	33.3% 1/3 • Number of events 1 • Up to 18 weeks	0.00% 0/2 • Up to 18 weeks

Additional Information

Gina G. Chung, MD

The Christ Hospital

Phone: (513) 564-7771

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place