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

NCT00054132 | Completed Phase 2 Results DMC

• 8 other identifiers: NCI-2013-02225CDR000026990002-119MSKCC-02119NCI-57615761N01CM17105P30CA008748
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 2

Brief Summary

This phase II trial studies how well erlotinib hydrochloride and bevacizumab work in treating patients with stage IV breast cancer. Erlotinib hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as bevacizumab, may interfere with the ability of tumor cells to grow and spread. Giving erlotinib hydrochloride and bevacizumab may be an effective treatment for breast cancer.

Conditions

Recurrent Breast Carcinoma; Stage IV Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Level of EGFR Expression

  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.

  Up to 12 years

• Response Rate, Defined as Complete Response (CR) + Partial Response (PR), Using the Response Evaluation Criteria in Solid Tumors

  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

  Up to 12 years

Secondary Outcomes (4)

• Duration of Response

  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

• Time to Progression

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

• Number of Patients Evaluated for Toxicity

  up to 12 years

• Participants With Duration of Stable Disease Greater Than or Equal to 6 Months

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

Other Outcomes (11)

• HER2 Status

  Up to 12 years

• Percentage of Cells Staining Positive for EGFR

  Up to 12 years

• Percentage of Cells Staining Positive for Human Epidermal Growth Factor Receptor 3 (HER3)

  Up to 12 years

Study Arms (1)

Treatment (erlotinib hydrochloride, bevacizumab)

EXPERIMENTAL

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.

Biological: Bevacizumab; Drug: Erlotinib Hydrochloride; Other: Laboratory Biomarker Analysis

Interventions

Bevacizumab BIOLOGICAL

Given IV

Also known as: Anti-VEGF, Anti-VEGF Humanized Monoclonal Antibody, Anti-VEGF rhuMAb, Avastin, Bevacizumab Biosimilar BEVZ92, Bevacizumab Biosimilar BI 695502, Immunoglobulin G1 (Human-Mouse Monoclonal rhuMab-VEGF Gamma-Chain Anti-Human Vascular Endothelial Growth Factor), Disulfide With Human-Mouse Monoclonal rhuMab-VEGF Light Chain, Dimer, Recombinant Humanized Anti-VEGF Monoclonal Antibody, rhuMab-VEGF

Treatment (erlotinib hydrochloride, bevacizumab)

Erlotinib Hydrochloride DRUG

Given PO

Also known as: Cp-358,774, OSI-774, Tarceva

Treatment (erlotinib hydrochloride, bevacizumab)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (erlotinib hydrochloride, bevacizumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically or cytologically confirmed carcinoma of the breast with metastatic (stage IV) disease that is currently stable or progressing after therapy
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as \>= 20 mm with conventional techniques or as \>= 10 mm with spiral computed tomography (CT) scan
• Patients must have either stable disease or disease progression on or after therapy with one or two conventional chemotherapy regimens for the treatment of metastatic (stage IV) breast cancer
• Prior treatment with high-dose chemotherapy and autologous stem cell/bone marrow transplantation is allowed, and is considered one prior regimen when administered for metastatic disease
• There is no restriction for the number of prior hormonal therapies or immunotherapies
• If human epidermal growth factor receptor 2 (Her2)/neu-positive (defined as 3+ by immunohistochemistry \[IHC\] or positive by fluorescence in situ hybridization \[FISH\]), prior therapy with trastuzumab required
• Any number of prior regimens of chemotherapy and/or hormonal therapy are allowed in the adjuvant setting, and do not count towards prior therapy when determining eligibility for this trial
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%)
• Life expectancy of greater than 3 months
• Leukocytes \>= 3,000/ul
• Absolute neutrophil count \>= 1,000/ul
• Platelets \>= 75,000/ul
• Total bilirubin within normal institutional limits
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\[) =\< 2.5 X institutional upper limit of normal
• Creatinine within normal institutional limits OR creatinine clearance \>= 60 mL/min for patients with creatinine levels outside institutional normal using the Cockcroft-Gault formula

You may not qualify if:

• Patients who have had chemotherapy, radiotherapy immunotherapy or investigational therapy within 3 weeks prior to starting treatment (6 weeks for nitrosoureas or mitomycin C), or hormonal therapy within 2 weeks prior to starting treatment
• Patients may not be receiving any other investigational agents
• History or evidence upon physical examination of central nervous system (CNS) disease (e.g., primary brain tumor, seizures not controlled with standard medical therapy, any brain metastases, or history of stroke); all subjects must have a baseline CT or magnetic resonance imaging (MRI) of the head
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to OSI-774 or bevacizumab
• Prior treatment with kinase insert domain receptor (KDR) inhibitors (e.g. vascular endothelial growth factor \[VEGF\] Trap, Su5416, Su6668, ZD6474, PTK757, IMC-1CII)
• Prior treatment with EGFR targeting therapies (e.g. ZD1839 or C225)
• Major surgery, open biopsy or significant traumatic injury occurring within 28 days prior to treatment; this does not apply to indwelling catheters, which require an interval of at least 24 hours between placement of the catheter and treatment with bevacizumab
• Current or recent (within 10 days prior to treatment) use of full-dose oral or parenteral anticoagulants or thrombolytic agents (except as required to maintain patency of preexisting, permanent indwelling IV catheters; for subjects receiving warfarin, international normalized ratio \[INR\] should be \< 1.5)
• Chronic daily treatment with aspirin (\> 325 mg/day) or nonsteroidal anti-inflammatory medications known to inhibit the platelet function (e.g. cyclooxygenase \[COX\]-1 inhibitors)
• Presence of bleeding diathesis or coagulopathy
• Cumulative anthracycline and anthracenedione exposure as follows: doxorubicin \> 450 mg/m\^2; epirubicin \> 700 mg/m\^2; liposomal doxorubicin \> 550 mg/m\^2; mitoxantrone \> 140 mg/m\^2
• Proteinuria at baseline; subjects unexpectedly discovered to have \>= 1+ proteinuria should undergo a 24-hour urine collection, which must be an adequate collection and must demonstrate =\< 500 mg protein/ 24 hours to allow participation in the study
• Cardiac ejection fraction (multigated acquisition scan \[MUGA\] or echocardiogram) less than the local institution lower limit of normal
• Abnormalities of the cornea based on history (e.g., dry eye syndrome, Sjögren's syndrome), congenital abnormality (e.g., Fuch's dystrophy), abnormal slit-lamp examination using a vital dye (e.g., fluorescein, Bengal-Rose), and/or an abnormal corneal sensitivity test (Schirmer test or similar tear production test)
• Serious, non-healing wound, ulcer, or bone fracture

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (2)

UCSF Medical Center-Mount Zion

San Francisco, California, 94115, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Bevacizumab; Immunoglobulin G; Disulfides; Erlotinib Hydrochloride

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Immunoglobulin Isotypes; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Maura Dickler
• Organization: Memorial Sloan Kettering Cancer Center

dicklerm@mskcc.org

646-888-4560

Study Officials

• Maura Dickler

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2003
• First Posted: February 6, 2003
• Study Start: December 1, 2002
• Primary Completion: April 1, 2015
• Study Completion: April 1, 2015
• Last Updated: July 24, 2017
• Results First Posted: July 24, 2017

Record last verified: 2017-06

Locations

US (2)