Lapatinib +/- Trastuzumab In Addition To Standard Neoadjuvant Breast Cancer Therapy.

NCT00524303 | Completed Phase 2 Results

• 1 other identifier: LPT109096
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 23

Brief Summary

This study will examine safety and efficacy of Lapatinib in combination with a standard neoadjuvant chemotherapy including 5FU, Epirubicin, Cyclophosphamide and Paclitaxel. Tumor tissue will be obtained at 3 timepoints (optional 4th) to evaluate tumor response to treatment.

Conditions

Neoplasms, Breast

Keywords

ErbB2 Overexpressing; ErbB2 Positive; Lapatinib; Invasive Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Overall Pathological Complete Response (pCR) After 26 Weeks of Therapy

  A pCR in the breast was defined as no pathologic evidence of invasive disease (residual ductal carcinoma in situ \[DCIS\] or lobular carcinoma in situ \[LCIS\] was allowed). A pCR in the axillary lymph node(s) was defined as no evidence of breast cancer cells in the lymph node (including subcapsular sinus). Overall pCR was defined as the sum of pCR in the breast and pCR in the lymph nodes. 26 weeks of therapy comprised the 2-week run-in phase, 12 weeks of treatment with FEC, and 12 weeks of treatment with Paclitaxel.

  Week 26

Secondary Outcomes (4)

• Percentage of Participants With Clinical Complete Response (cCR) at 26 Weeks or at End of Treatment (EOT) or Early Withdrawal

  Week 26 or EOT or Early withdrawal

• Percentage of Participants (Par.) With Disease-free Survival (DFS) at the End of 5 Years From Randomization

  From first dose date until disease progression, assessed up to a maximum of 5 years

• Number of Participants With the Indicated Electrocardiogram (ECG) Status at Baseline and at EOT or Early Withdrawal

  Baseline and EOT (up to Week 26) or Early withdrawal

• Cumulative Number of Participants With at Least One Decrease of More Than or Equal to 20% in Left Ventricular Ejection Fraction (LVEF) at the Indicated Time Points Compared to LVEF at Baseline

  Weeks 3, 9, and 15; EOT or early withdrawal; and 3- and 6-month survival follow-up after last chemotherapy course

Other Outcomes (3)

• Mean Intra-tumoral Expression of the Indicated Proteins at Baseline and Day 14

  Tumor core biopsy taken at Baseline and Treatment Day 14

• Cancer Stem Cells and the Correlation to Response/Non-response to Treatment

  Tumor core biopsy taken at Baseline and Treatment Day 14

• Transcriptional Profiling of Total RNA and the Correlation to Response/Non-response to Treatment

  Tumor core biopsy taken at Baseline and Treatment Day 14

Study Arms (3)

Arm 1

ACTIVE COMPARATOR

Trastuzumab alone for 2 weeks then in combination with FEC75 for 4 (21 Day) cycles and Paclitaxel for 4 (21 day) cycles then continued trastuzumab until time of definitive surgery

Drug: Trastuzumab; Drug: Paclitaxel; Drug: FEC75

Arm 2

EXPERIMENTAL

Lapatinib alone for 2 weeks then in combination with FEC75 for 4 (21 Day) cycles followed by Paclitaxel for 4 (21 day) cycles then continued lapatinib until time of definitive surgery

Drug: Paclitaxel; Drug: FEC75; Drug: Lapatinib

Arm 3

EXPERIMENTAL

Trastuzumab + Lapatinib for 2 weeks then added FEC75 for 4 (21 Day) cycles followed by Paclitaxel for 4 (21 day) cycles then continued trastuzumab + lapatinib until time of definitive surgery

Drug: Trastuzumab; Drug: Paclitaxel; Drug: FEC75; Drug: Lapatinib

Interventions

Trastuzumab DRUG

4mg/kg IV loading dose followed by 2mg/kg IV weekly

Arm 1; Arm 3

Paclitaxel DRUG

80mg/m2 IV weekly for 4 (21 day) cycles

Arm 1; Arm 2; Arm 3

FEC75 DRUG

5FU 500mg/m2 + Epirubicin 75 mg/m2 + cyclophosphamide 500 mg/m2 IV on day 1 of 4 (21 day) cycles

Arm 1; Arm 2; Arm 3

Lapatinib DRUG

1250 mg oral daily dose in arm 2, 750 mg oral daily dose for FEC cycles and then 1000 mg oral daily dose during the Paclitaxel cycles in arm 3

Arm 2; Arm 3

Eligibility Criteria

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

You may qualify if:

• Have signed an informed consent form (ICF) and a Patient Authorization Form (HIPAA).
• Have histologically or cytologically confirmed ErbB2- (HER2/neu-) overexpressing invasive breast cancer (T2-4, N0-2).
• ErbB2 overexpressing breast cancer, defined as one of the following definitions:
• + staining by immunohistochemistry (IHC),
• a fluorescent in situ hybridization (FISH) result of more than six HER2 gene copies per nucleus
• a FISH ratio of more than 2.2.
• Have either measurable or evaluable disease.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1 (Refer to Section 11.4).
• Have LVEF within the institutional range of normal as measured by either echocardiogram (ECHO) or MUGA scans. The same modality must be used consistently throughout the study.
• Be deemed able to tolerate 8 cycles of preoperative chemotherapy, including 4 cycles with an anthracycline (epirubicin).
• Must be willing to undergo 2 mandatory core biopsies (4 passes each) after diagnosis to obtain tissue for biologic expression profiling. Any subject with clinically palpable residual disease may undergo an optional third biopsy to allow identification of presumed pathways of resistance to therapy. This information might be useful in providing the subject with options for other targeted therapies if definitive surgery confirms residual disease. Definitive local therapy with surgery and radiation therapy as indicated will be performed after completion of 12 weeks of paclitaxel-based chemotherapy.
• Are able to swallow and retain oral medication (intact pill).
• Are able to complete all screening assessments as outlined in the protocol.
• Have adequate organ function as defined in Table 4:
• Table 1 Baseline Laboratory Values

You may not qualify if:

• Have received any prior chemotherapy.
• Had prior therapy with an ErbB1 and/or ErbB2 inhibitor.
• Are receiving concurrent anti-cancer therapy (chemotherapy, immunotherapy, and biologic therapy) while taking study medication.
• Have malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. Women with ulcerative colitis are also excluded.
• Have a concurrent disease or condition that would make the woman inappropriate for study participation, or any serious medical disorder that would interfere with the woman's safety.
• Have an active or uncontrolled infection.
• Have dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent.
• Have active cardiac disease, defined as one or more of the following:
• History of uncontrolled or symptomatic angina History of arrhythmias requiring medications, or clinically significant Myocardial infarction \<6 months from study entry Uncontrolled or symptomatic congestive heart failure Ejection fraction below the institutional normal limit Any other cardiac condition, which in the opinion of the treating physician, would make this protocol unreasonably hazardous for the patient
• Are pregnant or breastfeeding.
• Have received concurrent treatment with an investigational agent or participate in another clinical trial.
• Have received concurrent treatment with prohibited medications (refer to Section 5.8.2 for details on prohibited medications).
• Have used an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of study medication.
• Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to any of the agents used in this study or their excipients.
• Are receiving therapeutic anti-coagulation therapy (i.e. warfarin, heparin).

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (23)

GSK Investigational Site

Fountain Valley, California, 92708, United States

Location

GSK Investigational Site

Los Angeles, California, 90057, United States

Location

GSK Investigational Site

Denver, Colorado, 80220, United States

Location

GSK Investigational Site

Hudson, Florida, 34667, United States

Location

GSK Investigational Site

Miami, Florida, 33176, United States

Location

GSK Investigational Site

Pembroke Pines, Florida, 33028, United States

Location

GSK Investigational Site

Indianapolis, Indiana, 46219, United States

Location

GSK Investigational Site

Henderson, Nevada, 89052, United States

Location

GSK Investigational Site

Philadelphia, Pennsylvania, 19107, United States

Location

GSK Investigational Site

Austin, Texas, 78731, United States

Location

GSK Investigational Site

Beaumont, Texas, 77702-1449, United States

Location

GSK Investigational Site

Bedford, Texas, 76022, United States

Location

GSK Investigational Site

Dallas, Texas, 75231, United States

Location

GSK Investigational Site

Dallas, Texas, 75246, United States

Location

GSK Investigational Site

Dallas, Texas, 75320-2510, United States

Location

GSK Investigational Site

El Paso, Texas, 79915, United States

Location

GSK Investigational Site

Houston, Texas, 77024, United States

Location

GSK Investigational Site

Lewisville, Texas, 75067, United States

Location

GSK Investigational Site

Sugar Land, Texas, 77479, United States

Location

GSK Investigational Site

Tyler, Texas, 75702, United States

Location

GSK Investigational Site

Norfolk, Virginia, 23502, United States

Location

GSK Investigational Site

Seattle, Washington, 98117, United States

Location

GSK Investigational Site

Yakima, Washington, 98902, United States

Location

Related Publications (2)

• O'Shea J, Cremona M, Morgan C, Milewska M, Holmes F, Espina V, Liotta L, O'Shaughnessy J, Toomey S, Madden SF, Carr A, Elster N, Hennessy BT, Eustace AJ. A preclinical evaluation of the MEK inhibitor refametinib in HER2-positive breast cancer cell lines including those with acquired resistance to trastuzumab or lapatinib. Oncotarget. 2017 Jul 22;8(49):85120-85135. doi: 10.18632/oncotarget.19461. eCollection 2017 Oct 17.

  PMID: 29156708 DERIVED

• Holmes FA, Espina V, Liotta LA, Nagarwala YM, Danso M, McIntyre KJ, Osborne CR, Anderson T, Krekow L, Blum JL, Pippen J, Florance A, Mahoney J, O'Shaughnessy JA. Pathologic complete response after preoperative anti-HER2 therapy correlates with alterations in PTEN, FOXO, phosphorylated Stat5, and autophagy protein signaling. BMC Res Notes. 2013 Dec 5;6:507. doi: 10.1186/1756-0500-6-507.

  PMID: 24304724 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Trastuzumab; Paclitaxel; Lapatinib

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; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 31, 2007
• First Posted: September 3, 2007
• Study Start: August 1, 2007
• Primary Completion: October 1, 2010
• Study Completion: August 1, 2015
• Last Updated: November 11, 2016
• Results First Posted: August 11, 2011

Record last verified: 2016-03

Locations

US (23)