Defining the HER2 Positive (+) Breast Cancer Kinome Response to Trastuzumab, Pertuzumab, Combination Trastuzumab +Pertuzumab, or Combination Trastuzumab + Lapatinib

NCT01875666 | Completed Early Phase 1 DMC

• 1 other identifier: LCCC 1214
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 5

Brief Summary

Kinases are a group of proteins that are important in how cancer cells grow. HER2 is a kind of kinase. This study looks at a new approach to identifying kinases, which may help target therapy more precisely. LCCC1214 is a randomized, multiarm, multicenter, open-label window trial designed to explore the kinome response in Stage I-IV HER2 positive (HER2+) breast cancer patients scheduled to undergo definitive surgery (either lumpectomy, mastectomy or surgical resection of oligometastatic disease). Patients will initiate dosing with either a single HER2-directed agent or a combination of two HER2-directed agents, one week prior to surgery. Forty patients will be randomized to one of four study groups: A) single dose trastuzumab; B) single dose pertuzumab; C) combination single dose trastuzumab plus single dose pertuzumab; or D) combination single dose trastuzumab plus lapatinib daily for 7 days. Pre- and post- dosing tissue will be analyzed for kinome response and resistant signatures. The initiation of study drug will be defined by the surgical schedule; there will be no delays in standard treatment for the purposes of this study.

Conditions

Breast Neoplasms

Keywords

breast cancer; Kinome; HER two positive

Outcome Measures

Primary Outcomes (1)

• difference in kinome activation pre and post treatment

  To identify differential kinome activation before and after treatment with a single dose of trastuzumab, pertuzumab, the combination of trastuzumab + pertuzumab, or the combination of single dose trastuzumab+once daily lapatinib for 7 days, in patients with HER2+ breast cancer

  7-10 days prior to surgery and at surgery

Secondary Outcomes (1)

• predictability in kinome activation

  kinoming analysis of tissue will be done after subject participation, which will last from 7-10 days prior to surgery.

Other Outcomes (2)

• number and type of adverse reactions

  subjects will be followed for AEs during the one week to 10 days (mode expected to be 7 days) prior to surgery

• future predictive molecular markers in response to each treatment

  one year

Study Arms (4)

Trastuzumab

ACTIVE COMPARATOR

single dose intravenous infusion administration of trastuzumab (8 mg/kg)

Drug: Trastuzumab

pertuzumab

ACTIVE COMPARATOR

single dose infusion of pertuzumab (840 mg)

Drug: pertuzumab

trastuzumab plus pertuzumab

ACTIVE COMPARATOR

single dose infusion of combination trastuzumab (8 mg/kg) plus pertuzumab (840 mg)

Drug: Trastuzumab; Drug: pertuzumab

trastuzumab plus lapatinib

ACTIVE COMPARATOR

combination of single dose infusion of trastuzumab (8 mg/kg) plus oral lapatinib (1000 mg daily for 7 days)

Drug: Trastuzumab; Drug: lapatinib

Interventions

Trastuzumab DRUG

8 mg/kg IV, single dose

Also known as: Herceptin

Trastuzumab; trastuzumab plus lapatinib; trastuzumab plus pertuzumab

pertuzumab DRUG

840 mg IV single dose

Also known as: Perjeta

pertuzumab; trastuzumab plus pertuzumab

lapatinib DRUG

1000 mg daily for 7 days

Also known as: Tykerb

trastuzumab plus lapatinib

Eligibility Criteria

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

You may qualify if:

• Signed, written informed consent
• Age \>/= 18 years
• Histologically confirmed HER2+ breast cancer: IHC 3+ or fluorescence in situ hybridization \[FISH\] amplified; by clinical assay on either primary or metastatic tumor
• Stage I-IV disease
• For patients with Stage I-IIIc disease:
• Scheduled for lumpectomy or mastectomy
• No prior or current therapy for breast cancer
• Not considered a candidate for therapeutic neoadjuvant treatment
• For patients with Stage IV disease:
• Scheduled for surgical resection of oligometastatic disease
• Previously untreated for breast cancer
• Normal relevant end organ function as defined by the following:
• ANC\>1500 cells/mL
• Platelets \> 100,000 cells/mL
• Hemoglobin \> 10 g/dL

You may not qualify if:

• Pregnant or lactating female
• Prior radiation therapy to the target lesion
• Use of any investigational drug within 28 days or five half-lives, whichever is shorter, prior to the first dose of study medication; a minimum of 10 days between termination of the investigational drug and treatment with study medication is required
• Any major radiotherapy, tumor-directed systemic or immunotherapy within the last 4 weeks for any indication
• Candidate for therapeutic neoadjuvant treatment
• Active infection
• Evidence of severe or uncontrolled systemic diseases (e.g., unstable or uncompensated respiratory, hepatic, renal, or cardiac disease)
• Required administration of concomitant moderate or strong inhibitors or inducers of CYP3A4 for 14 days prior to the first dose of study drug prior amiodarone for up to 6 months prior to day 1 of study treatment
• Inability to take oral medications e.g., impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral medications (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection)
• History or evidence of cardiovascular risk including any of the following:
• Current uncontrolled hypertension (systolic \>150 mm Hg and/or diastolic \>100 mmHg) or unstable angina
• History of serious cardiac arrhythmia requiring treatment (exceptions: atrial fibrillation, paroxysmal supraventricular tachycardia)
• History of myocardial infarction within 6 months of day 1 of dosing
• History of CHF of New York Heart Association (NYHA) criteria
• Known human immunodeficiency virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection (with the exception of chronic or cleared HBV and HCV infection which will be allowed)

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead
• Genentech, Inc.: collaborator
• Susan G. Komen Breast Cancer Foundation: collaborator
• GlaxoSmithKline: collaborator

Study Sites (5)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

IU Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Lineberger Comprehensive Cancer Center, UNC

Chapel Hill, North Carolina, 27599, United States

Location

MD Anderson

Houston, Texas, 77030-4008, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Trastuzumab; pertuzumab; 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; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Lisa A Carey, MD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 4, 2013
• First Posted: June 12, 2013
• Study Start: August 5, 2013
• Primary Completion: December 19, 2016
• Study Completion: December 19, 2016
• Last Updated: September 4, 2020

Record last verified: 2020-07

Locations

US (5)