ErbB2 Over-expressing Metastatic Breast Cancer Study Using Paclitaxel, Trastuzumab, and Lapatinib

NCT ID: NCT00272987

Last Updated: 2023-04-28

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 63 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-12-13
• Study Completion Date: 2019-10-21

Brief Summary

This study was originally designed as a Phase III randomized, double blind, placebo controlled study to assess the safety and tolerability, and efficacy of paclitaxel plus trastuzumab plus lapatinib compared with paclitaxel plus trastuzumab plus placebo in women with ErbB2 overexpressing metastatic breast cancer. The planned study was a two stage design with an initial open-label safety stage to be conducted in approximately 65 subjects followed by a randomized phase conducted in a further 700 subjects. The open-label part of the study sequentially enrolled three cohorts with patients receiving a different dose combination of paclitaxel, trastuzumab and lapatinib. Following poor recruitment rate in the open label stage, the randomized stage of the study was terminated, thus no subjects were enrolled into the randomization stage.

Detailed Description

The primary objective of this study was to evaluate and compare time to progression (TTP). The Primary objective for open label phase was to determine the safety and tolerability of lapatinib when administered in combination with both paclitaxel and trastuzumab. The study first enrolled an open label safety cohort of 20 patients to assess the tolerability of the triplet combination. This was a 1 arm, 3 cohort study stage.

Open-label Phase: Patients were sequentially enrolled into three cohorts and received an open-label combination of paclitaxel, trastuzumab and lapatinib: Cohort 1 received paclitaxel 80mg/m2 IV weekly for 3 weeks of a 4 week cycle, trastuzumab 4 mg/kg IV loading dose and 2 mg/kg IV weekly, and lapatinib 1000 mg PO daily. Cohort 2 received paclitaxel 70mg/m2 IV weekly for 3 weeks of a 4 week cycle, trastuzumab 4 mg/kg IV loading dose and 2 mg/kg IV weekly, and lapatinib 1000 mg PO daily. Cohort 3 paclitaxel 80mg/m2 IV weekly for 3 weeks of a 4 week cycle, trastuzumab 4 mg/kg IV loading dose and 2 mg/kg IV weekly, and lapatinib 750 mg PO daily.

Randomized Phase: was terminated following the poor recruitment rate in the open-label safety stage. No subjects were enrolled into the randomization stage.

In summary, at approximately 3.5 years the primary analysis which included demographics, efficacy and safety were conducted; at approximately 7 years protocol amendment 7 cancelled collection of efficacy endpoints, and only key safety endpoints were to be collected; the final analysis was performed at approximately 14 years.

Conditions

Neoplasms, Breast

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1

Participants received: paclitaxel 80mg/m2 IV weekly for 3 weeks of a 4 week cycle plus trastuzumab 4 mg/kg IV loading dose and 2 mg/kg IV weekly plus lapatinib 1000 mg PO daily

Group Type: EXPERIMENTAL

lapatinib

Intervention Type: DRUG

(GW572016) 1000 mg QD

paclitaxel

Intervention Type: DRUG

80 mg/m2 IV weekly for three weeks

trastuzumab

Intervention Type: DRUG

4 mg/kg loading dose and 2 mg/kg weekly IV

Cohort 2

Participants received paclitaxel 70mg/m2 IV weekly for 3 weeks of a 4 week cycle plus trastuzumab 4 mg/kg IV loading dose and 2 mg/kg IV weekly plus lapatinib 1000 mg PO daily.

Group Type: EXPERIMENTAL

lapatinib

Intervention Type: DRUG

(GW572016) 1000 mg QD

paclitaxel

Intervention Type: DRUG

80 mg/m2 IV weekly for three weeks

trastuzumab

Intervention Type: DRUG

4 mg/kg loading dose and 2 mg/kg weekly IV

Cohort 3

Participants in this arm received 80mg/m2 IV weekly for 3 weeks of a 4 week cycle plus trastuzumab 4 mg/kg IV loading dose and 2 mg/kg IV weekly plus lapatinib 750 mg PO

Group Type: EXPERIMENTAL

lapatinib

Intervention Type: DRUG

(GW572016) 1000 mg QD

paclitaxel

Intervention Type: DRUG

80 mg/m2 IV weekly for three weeks

trastuzumab

Intervention Type: DRUG

4 mg/kg loading dose and 2 mg/kg weekly IV

Interventions

lapatinib

(GW572016) 1000 mg QD

Intervention Type: DRUG

paclitaxel

80 mg/m2 IV weekly for three weeks

Intervention Type: DRUG

trastuzumab

4 mg/kg loading dose and 2 mg/kg weekly IV

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Histologically confirmed invasive breast cancer with stage IV disease
• If trastuzumab was administered in the adjuvant setting, >12 months must have elapsed since discontinuation of trastuzumab therapy
• If a taxane was administered in the neoadjuvant or adjuvant setting, progression must have occurred ≥12 months after completion of this treatment
• Had tumors that overexpress ErbB2 defined as either: 3+ by IHC OR c-erbB2 gene amplification by FISH OR 0, 1+, 2+ by IHC and c-erbB2 gene amplification by FISH.
• Patients must have tumor tissue available for central testing, and must have Measurable lesion(s) according to RECIST
• Subjects must be females of at least 18 years Non-childbearing potential or Childbearing potential but using adequate contraception
• Radiotherapy to a limited area other than the sole site of measurable and assessable disease is allowed; however, patients must have completed treatment and recovered from all acute treatment-related toxicities prior to administration of the first dose of study medication
• Bisphosphonate therapy for bone metastases is allowed; however, treatment must be initiated prior to the first dose of randomized therapy. Prophylactic use of bisphosphonates in patients without bone disease is not permitted, except for the treatment of osteoporosis
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 1
• For those patients whose disease is estrogen receptor positive+ and/or progesterone receptor + one the following criteria should be met: Patients with visceral disease that requires chemotherapy (eg., patients with liver or lung metastases) or Rapidly progressing/life threatening disease, as determined by the investigator or Patients who received hormonal therapy and are no longer benefiting from this therapy;
• Able to swallow and retain oral medication
• Cardiac ejection fraction within institutional range of normal
• Patient must have adequate organ function

Exclusion Criteria

• Pregnant or lactating females;
• Received prior chemotherapy, immunotherapy, biologic therapy, or anti-ErbB1/ErbB2 therapy for metastatic disease, prior hormonal therapy is permitted but must be discontinued a minimum of 7 days prior to randomization;
• Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel. Patients with ulcerative colitis are also excluded;
• History of other malignancy; however, patients who have been disease-free for five years, or patients with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible;
• Concurrent disease or condition that would make the patient inappropriate for study participation, or any serious medical disorder that would interfere with the patient's safety;
• Unresolved or unstable, serious toxicity from prior administration of another investigational drug and/or of prior cancer treatment;
• Peripheral neuropathy of Grade 2 or greater;
• Active or uncontrolled infection;
• Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent;
• Known history of uncontrolled or symptomatic angina, arrhythmias, conduction abnormalities or congestive heart failure;
• Known history or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis;
• Concurrent cancer therapy (chemotherapy, radiation therapy, immunotherapy, biologic therapy, hormonal therapy);
• Concurrent treatment with an investigational agent or participation in another clinical trial;
• Concurrent treatment with any medication on the prohibited medications list.
• Used an investigational drug within 30 days or 5 half-lives, whichever is longer, preceding the first dose of treatment. Hormonal therapy needs to be discontinued at least 7 days before the first dose of treatment.
• Prior therapy with an ErbB2 inhibitor, other than trastuzumab in the adjuvant setting;
• A known immediate or delayed hypersensitivity reaction to drugs chemically related to lapatinib or excipients;
• A known immediate or delayed hypersensitivity reaction to drugs chemically related to paclitaxel or excipients;
• A known immediate or delayed hypersensitivity reaction to drugs chemically related to trastuzumab or excipients;
• Non compliance with any of the screening procedures

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Novartis Investigative Site

Roswell, Georgia, United States

Novartis Investigative Site

Joliet, Illinois, United States

Novartis Investigative Site

Detroit, Michigan, United States

Novartis Investigative Site

Jackson, Mississippi, United States

Novartis Investigative Site

Voorhees Township, New Jersey, United States

Novartis Investigative Site

Winston-Salem, North Carolina, United States

Novartis Investigative Site

Canton, Ohio, United States

Novartis Investigative Site

Columbus, Ohio, United States

Novartis Investigative Site

Middletown, Ohio, United States

Novartis Investigative Site

Charleston, South Carolina, United States

Novartis Investigative Site

Amarillo, Texas, United States

Novartis Investigative Site

Houston, Texas, United States

Novartis Investigative Site

Houston, Texas, United States

Novartis Investigative Site

Richmond, Virginia, United States

Novartis Investigative Site

Arlon, , Belgium

Novartis Investigative Site

Liège, , Belgium

Countries

United States; Belgium

References

Esteva FJ, Franco SX, Hagan MK, Brewster AM, Somer RA, Williams W, Florance AM, Turner S, Stein S, Perez A. An open-label safety study of lapatinib plus trastuzumab plus paclitaxel in first-line HER2-positive metastatic breast cancer. Oncologist. 2013 Jun;18(6):661-6. doi: 10.1634/theoncologist.2012-0129. Epub 2013 May 22.

Reference Type: BACKGROUND

PMID: 23697602 (View on PubMed)

Other Identifiers

2005-003432-22

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CLAP016A2301

Identifier Type: OTHER

Identifier Source: secondary_id

EGF104383

Identifier Type: -

Identifier Source: org_study_id