Phase 2 Neoadjuvant Doxorubicin and Cyclophosphamide -> Docetaxel With Lapatinib in Stage II/III Her2Neu+ Breast Cancer

NCT00404066 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: IRB-03518BRSADJ0002
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 2

Brief Summary

This trial combines dose dense chemotherapy with doxorubicin and cyclophosphamide (AC) followed by standard, every 3 week docetaxel and GW572016 (lapatinib) for neoadjuvant treatment of Her2neu positive stage II/III breast cancer. The purpose of the study was to determine whether lapatinib combined with chemotherapy was safe and resulted in an increase in pathologic complete response rates.

Conditions

Breast Cancer; Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Pathologic Complete Response (pCR)

  Pathologic Complete Response (pCR) rate, assessed as no evidence of invasive disease in excised surgical specimens of breast and/or axilla, in participants who received at least 1 cycle of docetaxel and lapatinib and at least one follow-up evaluation.

  12 weeks

Secondary Outcomes (1)

• Disease-free Survival (DFS)

  42 months (median follow-up)

Study Arms (1)

Neoadjuvant Chemotherapy

EXPERIMENTAL

Doxorubicin (Adriamycin) + cyclophosphamide (Cytoxan) with pegfilgrastim or filgrastim growth factor support every 2 weeks for 4 cycles, followed by docetaxel + lapatinib for four 21-day cycles, followed by surgery. Dexamethasone was administered twice-a-day for 3 days, starting 24 hours before the docetaxel infusions. After surgery +/- radiation, participants may receive trastuzumab (Herceptin) for a year.

Drug: Lapatinib; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Docetaxel; Drug: Pegfilgrastim; Drug: Filgrastim; Drug: Dexamethasone; Drug: Trastuzumab

Interventions

Lapatinib DRUG

1250 mg, tablets, oral daily during treatment with docetaxel (3-week cycles x 4 cycles)

Also known as: GW572016

Neoadjuvant Chemotherapy

Doxorubicin DRUG

60 mg/m2, intravenously every 2 weeks for 4 cycles. Given as first treatment with cyclophosphamide.

Also known as: Adriamycin, Adriablastin

Neoadjuvant Chemotherapy

Cyclophosphamide DRUG

600 mg/m2, intravenously every 2 weeks for 4 cycles. Given as first treatment with doxorubicin.

Also known as: Cytoxan, ASTA

Neoadjuvant Chemotherapy

Docetaxel DRUG

100 mg/m2, intravenously every 3 weeks for 4 cycles (after treatment cycles of doxorubicin and cyclophosphamide

Also known as: Taxotere

Neoadjuvant Chemotherapy

Pegfilgrastim DRUG

6 mg, subcutaneously on day 2 of all cytotoxic chemotherapy treatments.

Also known as: Neulasta

Neoadjuvant Chemotherapy

Filgrastim DRUG

300 or 480 mcg, subcutaneously on days 3 to 10 after cytotoxic chemotherapies.

Also known as: Neupogen, Granulocyte Colony-Stimulating Factor (G-CSF)

Neoadjuvant Chemotherapy

Dexamethasone DRUG

8 mg, oral taken twice a day for 3 days starting 24 hours before docetaxel

Also known as: Adexone

Neoadjuvant Chemotherapy

Trastuzumab DRUG

Loading dose 8 mg/kg, then 6 mg/kg, intravenously every 3 weeks for 1 year

Also known as: Herceptin

Neoadjuvant Chemotherapy

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female
• Histologically-confirmed Her2neu positive breast cancer, by either Immunohistochemistry (IHC) 3+ or Fluorescence In Situ Hybridization (FISH)+
• Stage II/III breast cancer including any large primary tumor (\> 2 cm), tumors of any size associated with skin or chest wall involvement, tumors of any size with axillary lymph node involvement, (T2-T4, N0-N2) and those with ipsilateral subclavicular or supraclavicular lymph nodes).
• At least one bi-dimensional, measurable indicator lesion.
• Between 18 and 70 years of age
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 / Karnofsky ≥ 60% at screening and on the first day of treatment.
• Informed consent must be obtained prior to registration.
• Cardiac ejection fraction within the institutional range of normal as measured by multigated acquisition (MUGA) or echocardiography (ECHO) scan.
• Absolute neutrophil count \> 1,500/mm³
• Hemoglobin \> 8.0 g/dL
• Platelet count \> 100,000/mm³
• Creatinine within normal institutional limits
• Total Bilirubin equal to or less than institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST); alanine aminotransferase (ALT); and alkaline phosphatase must be within the range allowing for eligibility. In determining eligibility the more abnormal of the two values (AST or ALT) should be used.
• Eligibility of patients receiving medications or substances known to affect, or with the potential to affect the activity or pharmacokinetics of GW572016 will be determined following review of their use by the Principal Investigator

You may not qualify if:

• Evidence of disease outside the breast or chest wall, except for ipsilateral axillary , supraclavicular, or infraclavicular lymph nodes.
• Prior chemotherapy, immunotherapy, or hormonal therapy for breast cancer.
• More than 3 months between histologic diagnosis and registration on this study.
• History of other malignancy within the last 5years, except curatively treated basal cell carcinoma of the skin or carcinoma in situ of the cervix.
• Psychological, familial, sociological or geographical conditions which do not permit weekly medical follow-up and compliance with the study protocol. Those who are medically-unstable, including but not limited to active infection, acute hepatitis, deep vein thrombosis requiring anticoagulant therapy, gastrointestinal bleeding, uncontrolled hypercalcemia, uncontrolled diabetes, dementia, seizures, superior vena cava syndrome, and those whose circumstances do not permit completion of the study or the required follow-up.
• Congestive heart failure, abnormal left ventricular ejection fraction (LVEF), angina pectoris, uncontrolled cardiac arrhythmias, or other significant heart disease, or who have had a myocardial infarction within the past year.
• Pregnant or lactating
• Of childbearing potential and not employing adequate contraception
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to GW572016.
• HIV-positive and receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with lapatinib. Appropriate studies will be undertaken in patients receiving combination anti-retroviral therapy when indicated.
• GI tract disease resulting in an inability to take oral medication, malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease (e.g., Crohn's, ulcerative colitis).
• History of severe hypersensitivity reaction to taxotere or other drugs formulated with polysorbate 80.
• Current active hepatic or biliary disease (with exception of patients with Gilberts syndrome, asymptomatic gallstones, or stable chronic liver disease per investigator assessment ).

Sponsors & Collaborators

• George Albert Fisher: lead
• GlaxoSmithKline: collaborator
• Sanofi: collaborator

Study Sites (2)

Santa Clara Valley Medical Center

San Jose, California, 95128, United States

Location

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Lapatinib; Doxorubicin; Cyclophosphamide; Docetaxel; pegfilgrastim; Filgrastim; Granulocyte Colony-Stimulating Factor; Dexamethasone; Calcium Dobesilate; Trastuzumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: George Albert Fisher, MD, PhD
• Organization: Stanford University Medical Center

georgeaf@stanford.edu

650-725-9057

Study Officials

• George A Fisher, MD, PhD

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: November 22, 2006
• First Posted: November 27, 2006
• Study Start: October 1, 2006
• Primary Completion: December 1, 2010
• Study Completion: March 1, 2011
• Last Updated: December 22, 2017
• Results First Posted: December 22, 2017

Record last verified: 2017-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)