Trial Outcomes & Findings for Erlotinib Hydrochloride and Bevacizumab in Treating Patients With Stage IV Breast Cancer (NCT NCT00054132)

NCT ID: NCT00054132

Last Updated: 2017-07-24

Results Overview

Estimated at the end of the trial Immunoreactivity will be evaluated qualitatively with regard to intensity as follows: Measured on a scale, ranging from 0-3+ 0=negative (no immunoreactivity) 1+ - 3+ = positive: * faint immunoreactivity (weak staining) * intense immunoreactivity (strong staining) Immunohistochemical studies will be performed on the tumor specimen to correlate the anti-tumor efficacy of OSI-774 and bevacizumab with pre-treatment molecular characteristics.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 38 participants
• Primary outcome timeframe: Up to 12 years
• Results posted on: 2017-07-24

Participant Flow

Participant milestones

Measure	Treatment (Erlotinib Hydrochloride, Bevacizumab) Patients receive erlotinib hydrochloride PO QD on days 1-21 and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Overall Study STARTED	38
Overall Study COMPLETED	37
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Measure	Treatment (Erlotinib Hydrochloride, Bevacizumab) Patients receive erlotinib hydrochloride PO QD on days 1-21 and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Overall Study Not Treated	1

Baseline Characteristics

Erlotinib Hydrochloride and Bevacizumab in Treating Patients With Stage IV Breast Cancer

Baseline characteristics by cohort

Measure	Treatment (Erlotinib Hydrochloride, Bevacizumab) n=38 Participants Patients receive erlotinib hydrochloride PO QD on days 1-21 and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Age, Categorical <=18 years	0 Participants n=93 Participants
Age, Categorical Between 18 and 65 years	34 Participants n=93 Participants
Age, Categorical >=65 years	4 Participants n=93 Participants
Sex: Female, Male Female	38 Participants n=93 Participants
Sex: Female, Male Male	0 Participants n=93 Participants
Region of Enrollment United States	38 participants n=93 Participants

PRIMARY outcome

Timeframe: Up to 12 years

Estimated at the end of the trial Immunoreactivity will be evaluated qualitatively with regard to intensity as follows: Measured on a scale, ranging from 0-3+ 0=negative (no immunoreactivity)

1+ - 3+ = positive:

• faint immunoreactivity (weak staining)
• intense immunoreactivity (strong staining) Immunohistochemical studies will be performed on the tumor specimen to correlate the anti-tumor efficacy of OSI-774 and bevacizumab with pre-treatment molecular characteristics.

Outcome measures

Measure	Treatment (Erlotinib Hydrochloride, Bevacizumab) n=38 Participants Patients receive erlotinib hydrochloride PO QD on days 1-21 and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Level of EGFR Expression EGFR 0	24 participants
Level of EGFR Expression EGFR 1+	8 participants
Level of EGFR Expression EGFR 2+	4 participants
Level of EGFR Expression EGFR 3+	0 participants
Level of EGFR Expression Insufficient tumor tissue	2 participants

PRIMARY outcome

Timeframe: Up to 12 years

Estimated at the end of the trial. Complete Response (CR):Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD 55 Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started

Outcome measures

Measure	Treatment (Erlotinib Hydrochloride, Bevacizumab) n=37 Participants Patients receive erlotinib hydrochloride PO QD on days 1-21 and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Response Rate, Defined as Complete Response (CR) + Partial Response (PR), Using the Response Evaluation Criteria in Solid Tumors Complete Response	0 participants
Response Rate, Defined as Complete Response (CR) + Partial Response (PR), Using the Response Evaluation Criteria in Solid Tumors Partial Response	1 participants
Response Rate, Defined as Complete Response (CR) + Partial Response (PR), Using the Response Evaluation Criteria in Solid Tumors Stable Disease	17 participants
Response Rate, Defined as Complete Response (CR) + Partial Response (PR), Using the Response Evaluation Criteria in Solid Tumors Progression of Disease	19 participants

SECONDARY outcome

Timeframe: From the time measurement criteria are met for CR and PR until the first date that recurrent or progressive disease is objectively documented, assessed up to 12 years

The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).Evaluation of Target Lesions Complete Response (CR):Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD

Outcome measures

Measure	Treatment (Erlotinib Hydrochloride, Bevacizumab) n=1 Participants Patients receive erlotinib hydrochloride PO QD on days 1-21 and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Duration of Response	52 months

SECONDARY outcome

Timeframe: From the start of treatment until the first date that recurrent or progressive disease is objectively documented, assessed up to 12 years

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

Outcome measures

Measure	Treatment (Erlotinib Hydrochloride, Bevacizumab) n=19 Participants Patients receive erlotinib hydrochloride PO QD on days 1-21 and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Time to Progression	11 weeks Interval 8.0 to 18.0

SECONDARY outcome

Timeframe: up to 12 years

Population: Please see adverse events section.

graded according to the National Cancer Institute Common Toxicity Criteria version 4.0

Outcome measures

Measure	Treatment (Erlotinib Hydrochloride, Bevacizumab) n=38 Participants Patients receive erlotinib hydrochloride PO QD on days 1-21 and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Number of Patients Evaluated for Toxicity	38 Participants

SECONDARY outcome

Timeframe: From the start of treatment until the first date that recurrent or progressive disease is objectively documented, assessed up to 12 years

Duration of stable disease greater than or equal to 6 months

Outcome measures

Measure	Treatment (Erlotinib Hydrochloride, Bevacizumab) n=17 Participants Patients receive erlotinib hydrochloride PO QD on days 1-21 and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Participants With Duration of Stable Disease Greater Than or Equal to 6 Months	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 12 years

Associations between response and HER2 will be assessed by Fisher's exact test.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 12 years

Associations between markers and tumor response will be assessed by logistic regression analysis. For those markers that are statistically significant, a cut-point analysis will be performed by the maximum chi-square with p-value adjustment method to determine positive values.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 12 years

Associations between markers and tumor response will be assessed by logistic regression analysis. For those markers that are statistically significant, a cut-point analysis will be performed by the maximum chi-square with p-value adjustment method to determine positive values.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 12 years

Associations between markers and tumor response will be assessed by logistic regression analysis. For those markers that are statistically significant, a cut-point analysis will be performed by the maximum chi-square with p-value adjustment method to determine positive values.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 12 years

Associations between markers and tumor response will be assessed by logistic regression analysis. For those markers that are statistically significant, a cut-point analysis will be performed by the maximum chi-square with p-value adjustment method to determine positive values.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 12 years

Associations between markers and tumor response will be assessed by logistic regression analysis. For those markers that are statistically significant, a cut-point analysis will be performed by the maximum chi-square with p-value adjustment method to determine positive values.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 12 years

Associations between markers and tumor response will be assessed by logistic regression analysis. For those markers that are statistically significant, a cut-point analysis will be performed by the maximum chi-square with p-value adjustment method to determine positive values.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 12 years

Associations between markers and tumor response will be assessed by logistic regression analysis. For those markers that are statistically significant, a cut-point analysis will be performed by the maximum chi-square with p-value adjustment method to determine positive values.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 12 years

Associations between markers and tumor response will be assessed by logistic regression analysis. For those markers that are statistically significant, a cut-point analysis will be performed by the maximum chi-square with p-value adjustment method to determine positive values.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 12 years

Associations between markers and tumor response will be assessed by logistic regression analysis. For those markers that are statistically significant, a cut-point analysis will be performed by the maximum chi-square with p-value adjustment method to determine positive values.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 12 years

Associations between markers and tumor response will be assessed by logistic regression analysis. For those markers that are statistically significant, a cut-point analysis will be performed by the maximum chi-square with p-value adjustment method to determine positive values.

Outcome measures

Outcome data not reported

Adverse Events

Treatment (Erlotinib Hydrochloride, Bevacizumab)

Serious events: 6 serious events

Other events: 32 other events

Deaths: 0 deaths

Serious adverse events

Measure	Treatment (Erlotinib Hydrochloride, Bevacizumab) n=38 participants at risk Patients receive erlotinib hydrochloride PO QD on days 1-21 and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
General disorders General disorders and administration site conditions-other, specify	5.3% 2/38 • Number of events 2
Metabolism and nutrition disorders Dehydration	2.6% 1/38 • Number of events 1
Gastrointestinal disorders Diarrhea	2.6% 1/38 • Number of events 1
Nervous system disorders Peripheral motor neuropathy	2.6% 1/38 • Number of events 1
Respiratory, thoracic and mediastinal disorders Dyspnea	2.6% 1/38 • Number of events 2
General disorders Pain, other	2.6% 1/38 • Number of events 2
Respiratory, thoracic and mediastinal disorders Pleural effusion	2.6% 1/38 • Number of events 1
Skin and subcutaneous tissue disorders Skin ulceration	2.6% 1/38 • Number of events 1
Vascular disorders Thrombosis	2.6% 1/38 • Number of events 1

Other adverse events

Measure	Treatment (Erlotinib Hydrochloride, Bevacizumab) n=38 participants at risk Patients receive erlotinib hydrochloride PO QD on days 1-21 and bevacizumab IV over 30-90 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Investigations Alanine aminotransferase increased	10.5% 4/38 • Number of events 6
Investigations Alkaline phosphatase increased	13.2% 5/38 • Number of events 6
Blood and lymphatic system disorders Anemia	7.9% 3/38 • Number of events 12
Musculoskeletal and connective tissue disorders Arthralgia	7.9% 3/38 • Number of events 3
Investigations Aspartate aminotransferase increased	10.5% 4/38 • Number of events 4
Investigations Blood bilirubin increased	21.1% 8/38 • Number of events 10
Eye disorders Blurred vision	5.3% 2/38 • Number of events 2
Respiratory, thoracic and mediastinal disorders Cough	5.3% 2/38 • Number of events 2
Metabolism and nutrition disorders Dehydration	5.3% 2/38 • Number of events 2
Gastrointestinal disorders Diarrhea	10.5% 4/38 • Number of events 4
Skin and subcutaneous tissue disorders Dry skin	5.3% 2/38 • Number of events 2
Gastrointestinal disorders Dyspepsia	7.9% 3/38 • Number of events 3
Respiratory, thoracic and mediastinal disorders Dyspnea	23.7% 9/38 • Number of events 10
General disorders Fatigue	10.5% 4/38 • Number of events 4
Metabolism and nutrition disorders Hyperglycemia	5.3% 2/38 • Number of events 3
Vascular disorders Hypertension	13.2% 5/38 • Number of events 5
Metabolism and nutrition disorders Hypocalcemia	7.9% 3/38 • Number of events 5
Infections and infestations Infections and infestations - Other, specify	18.4% 7/38 • Number of events 7
Investigations Lymphocyte count decreased	18.4% 7/38 • Number of events 19
Gastrointestinal disorders Mucositis oral	10.5% 4/38 • Number of events 6
Skin and subcutaneous tissue disorders Nail loss	5.3% 2/38 • Number of events 2
Gastrointestinal disorders Nausea	5.3% 2/38 • Number of events 2
Renal and urinary disorders Proteinuria	7.9% 3/38 • Number of events 5
Skin and subcutaneous tissue disorders Pruritus	5.3% 2/38 • Number of events 2
Skin and subcutaneous tissue disorders Rash maculo-papular	39.5% 15/38 • Number of events 16
Vascular disorders Thromboembolic event	10.5% 4/38 • Number of events 4
Skin and subcutaneous tissue disorders Urticaria	5.3% 2/38 • Number of events 3

Additional Information

Dr. Maura Dickler

Memorial Sloan Kettering Cancer Center

Phone: 646-888-4560

Email: dicklerm@mskcc.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60