Paclitaxel With Trastuzumab and Lapatinib in HER2-Positiv... | NCT01827163

NCT01827163

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

Status Module

Name	Class
GlaxoSmithKline	INDUSTRY

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Paclitaxel With Trastuzumab and Lapatinib	Experimental	Paclitaxel (T) at 175 mg/m2 q 2 weeks x 4 with filgrastim/pegfilgrastim + trastuzumab (H) + daily oral lapatinib (L), followed by trastuzumab q 3 weeks x 15 doses + daily oral lapatinib (HL). Pegfilgrastim 6mg will be given subcutaneously (SQ) on day # 2 of each paclitaxel administration. Filgrastim may be used in lieu of pegfilgrastim at physician's discretion. Trastuzumab will be administered weekly (4 mg/kg bolus followed by 2 mg/kg weekly) starting with paclitaxel treatment cycle # 1. After 4 cycles of paclitaxel, pts will receive trastuzumab on a q 3 weeks x 15 doses (to complete about one year). The q 3 week trastuzumab may be started from 1-3 weeks after the last dose of paclitaxel. A total of 15 infusions of trastuzumab will be given q 3 weeks after the completion of paclitaxel during the HL phase. Lapatinib will be given orally at 1000 mg daily, starting with paclitaxel during the THL phase & continued for the remaining year during the HL phase for about a year.	Drug: Paclitaxel Drug: Trastuzumab Drug: Lapatinib Drug: Pegfilgrastim

Name	Type	Description	Arm Group Labels	Other Names
Paclitaxel	Drug		Paclitaxel With Trastuzumab and Lapatinib
Trastuzumab

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number of Participants Who Are Able to Complete THL (Paclitaxel, Trastuzumab, and Lapatinib) Without a Dose Delay or Reduction, Grade 3 or Greater QTc Prolongation	The primary objective of this trial is to determine the feasibility of this regimen in patients with node-negative HER-2/neu overexpressed /amplified breast cancer with a tumor size of < 3 cm. The regimen is considered feasible if patients are able to complete the paclitaxel, trastuzumab, and lapatinib (THL) portion of the regimen without a dose delay or reduction or grade 3 or greater QTc prolongation.	1 year

Secondary Outcomes

Measure	Description	Time Frame
Participants Toxicity Evaluated While on Study Treatment	All toxicities following chemotherapy will be graded using the National Cancer Institute - Common Toxicity Criteria version 4.0.	1 year

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Patients must have histologically confirmed adenocarcinoma with HER2/neu immunohistochemistry 3+ or FISH-amplified breast cancer with a ratio of ≥ 2.0
Tumor size of ≤ 3 cm and node-negative disease. Nodes with single cells or tumor clusters < 0.2 mm by H&E or IHC are considered node-negative. Patients with micrometastasis (nodes with tumor clusters between 0.02 and 0.2 cm) are allowed. Further axillary dissection will be determined by the patient's surgeon as per standard of care.
Patients must be ≥18 years of age.
Patients must have an ECOG performance status of 0 or 1.
Treatment should be started within 90 days of the final surgical procedure for breast cancer.
Patients may have bilateral synchronous breast tumors. Patients may have received hormonal therapy for the purpose of chemoprevention but must be willing to discontinue prior to enrollment and while participating in this trial.
If patients have peripheral neuropathy, it must be ≤ grade 1.
Patients must be willing to discontinue sex hormonal therapy e.g., birth control pills, ovarian hormonal replacement therapy, etc., prior to enrollment. Women of childbearing potential must be willing to consent to using effective contraception while on treatment and for a reasonable period thereafter.
Hematologic parameters: absolute neutrophil count (ANC) ≥1500/μL and platelet count ≥100,000/μL.
Non-hematologic parameters: total bilirubin must be ≤ 1.5 X institutional upper limit of normal (ULN), transaminases (SGOT or SGPT) ≤ 3.0 x ULN.
Negative HCG pregnancy test for premenopausal women of reproductive capacity and for women less than 12 months after the menopause. LVEF by ECHO (with strain if possible) with LVEF of ≥ 50%. If an ECHO cannot be done, a MUGA may be performed.
Patients must give written, informed consent indicating their understanding of and willingness to participate in the study.

Exclusion Criteria:

Patients with stage IV breast cancer or undergoing chemotherapy, radiation therapy, immunotherapy, or biotherapy for current breast cancer.
Pregnant or breastfeeding patients.
Patients with a concurrently active second malignancy, other than adequately treated non-melanoma skin cancers or in situ cervical cancer.
Patients with unstable angina, congestive heart failure, or with a history of a myocardial infarction within 12 months. Patients with high-risk uncontrolled arrhythmias (ventricular tachycardia, high-grade AV block, supraventricular arrhythmias which are not adequately rate-controlled). Patients are excluded if they have grade 3 QT prolongation (Appendix F) (>500 ms) or require drugs that may prolong the QT.
Subjects who have current active hepatic (including hepatitis B or C) or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones).
Patients with active, unresolved infections.
Patients with a sensitivity to E. coli derived proteins.

Name	Affiliation	Role
Chau Dang, MD	Memorial Sloan Kettering Cancer Center	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Memorial Sloan Kettering Basking Ridge		Basking Ridge	New Jersey	07920	United States
Memorial Sloan-Kettering Cancer Commack

PubMed Identifier	Type	Citation	Retractions
26454612	Derived	Iyengar NM, Fornier MN, Sugarman SM, Theodoulou M, Troso-Sandoval TA, D'Andrea GM, Drullinsky PR, Gajria D, Goldfarb SB, Comen EA, Lake DE, Modi S, Traina TA, Lacouture ME, Chen MF, Patil S, Baselga J, Norton L, Hudis CA, Dang CT. A Pilot Study of Dose-Dense Paclitaxel With Trastuzumab and Lapatinib for Node-negative HER2-Overexpressed Breast Cancer. Clin Breast Cancer. 2016 Apr;16(2):87-94. doi: 10.1016/j.clbc.2015.09.009. Epub 2015 Sep 25.

Label	URL
Memorial Sloan-Kettering Cancer Center	View source

Arm/Group Information

ID	Title	Description
FG000	Paclitaxel With Trastuzumab and Lapatinib	Paclitaxel (T) at 175 mg/m2 q 2 weeks x 4 with filgrastim/pegfilgrastim + trastuzumab (H) + daily oral lapatinib (L), followed by trastuzumab q 3 weeks x 15 doses + daily oral lapatinib (HL). Pegfilgrastim 6mg will be given subcutaneously (SQ) on day # 2 of each paclitaxel administration. Filgrastim may be used in lieu of pegfilgrastim at physician's discretion. Trastuzumab will be administered weekly (4 mg/kg bolus followed by 2 mg/kg weekly) starting with paclitaxel treatment cycle # 1. After 4 cycles of paclitaxel, pts will receive trastuzumab on a q 3 weeks x 15 doses (to complete about one year). The q 3 week trastuzumab may be started from 1-3 weeks after the last dose of paclitaxel. A total of 15 infusions of trastuzumab will be given q 3 weeks after the completion of paclitaxel during the HL phase. Lapatinib will be given orally at 1000 mg daily, starting with paclitaxel during the THL phase & continued for the remaining year during the HL phase for about a year. Paclitaxel

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Paclitaxel With Trastuzumab and Lapatinib	Paclitaxel (T) at 175 mg/m2 q 2 weeks x 4 with filgrastim/pegfilgrastim + trastuzumab (H) + daily oral lapatinib (L), followed by trastuzumab q 3 weeks x 15 doses + daily oral lapatinib (HL). Pegfilgrastim 6mg will be given subcutaneously (SQ) on day # 2 of each paclitaxel administration. Filgrastim may be used in lieu of pegfilgrastim at physician's discretion. Trastuzumab will be administered weekly (4 mg/kg bolus followed by 2 mg/kg weekly) starting with paclitaxel treatment cycle # 1. After 4 cycles of paclitaxel, pts will receive trastuzumab on a q 3 weeks x 15 doses (to complete about one year). The q 3 week trastuzumab may be started from 1-3 weeks after the last dose of paclitaxel. A total of 15 infusions of trastuzumab will be given q 3 weeks after the completion of paclitaxel during the HL phase. Lapatinib will be given orally at 1000 mg daily, starting with paclitaxel during the THL phase & continued for the remaining year during the HL phase for about a year. Paclitaxel

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Median

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number of Participants Who Are Able to Complete THL (Paclitaxel, Trastuzumab, and Lapatinib) Without a Dose Delay or Reduction, Grade 3 or Greater QTc Prolongation

The primary objective of this trial is to determine the feasibility of this regimen in patients with node-negative HER-2/neu overexpressed /amplified breast cancer with a tumor size of < 3 cm. The regimen is considered feasible if patients are able to complete the paclitaxel, trastuzumab, and lapatinib (THL) portion of the regimen without a dose delay or reduction or grade 3 or greater QTc prolongation.

Posted

Count of Participants

Participants

1 year

ID	Title	Description
OG000	Paclitaxel With Trastuzumab and Lapatinib	Paclitaxel (T) at 175 mg/m2 q 2 weeks x 4 with filgrastim/pegfilgrastim + trastuzumab (H) + daily oral lapatinib (L), followed by trastuzumab q 3 weeks x 15 doses + daily oral lapatinib (HL). Pegfilgrastim 6mg will be given subcutaneously (SQ) on day # 2 of each paclitaxel administration. Filgrastim may be used in lieu of pegfilgrastim at physician's discretion. Trastuzumab will be administered weekly (4 mg/kg bolus followed by 2 mg/kg weekly) starting with paclitaxel treatment cycle # 1. After 4 cycles of paclitaxel, pts will receive trastuzumab on a q 3 weeks x 15 doses (to complete about one year). The q 3 week trastuzumab may be started from 1-3 weeks after the last dose of paclitaxel. A total of 15 infusions of trastuzumab will be given q 3 weeks after the completion of paclitaxel during the HL phase. Lapatinib will be given orally at 1000 mg daily, starting with paclitaxel during the THL phase & continued for the remaining year during the HL phase for about a year. Paclitaxel

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Paclitaxel With Trastuzumab and Lapatinib	Paclitaxel (T) at 175 mg/m2 q 2 weeks x 4 with filgrastim/pegfilgrastim + trastuzumab (H) + daily oral lapatinib (L), followed by trastuzumab q 3 weeks x 15 doses + daily oral lapatinib (HL). Pegfilgrastim 6mg will be given subcutaneously (SQ) on day # 2 of each paclitaxel administration. Filgrastim may be used in lieu of pegfilgrastim at physician's discretion. Trastuzumab will be administered weekly (4 mg/kg bolus followed by 2 mg/kg weekly) starting with paclitaxel treatment cycle # 1. After 4 cycles of paclitaxel, pts will receive trastuzumab on a q 3 weeks x 15 doses (to complete about one year). The q 3 week trastuzumab may be started from 1-3 weeks after the last dose of paclitaxel. A total of 15 infusions of trastuzumab will be given q 3 weeks after the completion of paclitaxel during the HL phase. Lapatinib will be given orally at 1000 mg daily, starting with paclitaxel during the THL phase & continued for the remaining year during the HL phase for about a year. Paclitaxel

ID	Term
D043823	Taxoids
D043822	Cyclodecanes
D003516	Cycloparaffins
D006840	Hydrocarbons, Alicyclic

ID	Term
D017239	Paclitaxel
D000068878	Trastuzumab
D000077341	Lapatinib
C455861	pegfilgrastim