- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00367471
Combination Of Lapatinib With Carboplatin, Paclitaxel, and With or Without Trastuzumab In Metastatic Breast Cancer.
September 8, 2020 updated by: Novartis Pharmaceuticals
A Phase I, Dose Escalation Study to Assess the Safety and Tolerability of Lapatinib in Combination With Carboplatin, Paclitaxel, With and Without Trastuzumab in Subjects With Metastatic Breast Cancer
The purpose of this study is to determine the optimally-tolerated regimens (OTR) for lapatinib in combination with paclitaxel, carboplatin with and without trastuzumab in patients with metastatic breast cancer.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
31
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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California
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La Jolla, California, United States, 92093-0987
- Novartis Investigative Site
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Indiana
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Indianapolis, Indiana, United States, 46202
- Novartis Investigative Site
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North Carolina
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Greensboro, North Carolina, United States, 27403
- Novartis Investigative Site
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion criteria:
- Subjects must have histologically- or cytologically-confirmed invasive breast cancer with Stage IV disease.
- Treatment Group A: Documentation of ErbB2 status (IHC 3+ or FISH+) in breast tumor specimens must be demonstrated before study enrollment. It is requested that archived breast tumor tissue be sent to a central laboratory for independent confirmation of ErbB2 status by FISH analysis.
- Treatment Group B: Documentation of ErbB2 status (IHC or FISH) in breast tumor specimen must be demonstrated before study enrollment. It is requested that archived breast tumor tissue be sent to a central laboratory for independent confirmation of ErbB2 status (FISH analysis).
- Subjects must be ≥18 years of age.
- Male or female
Criteria for female subjects:
- Non-child-bearing potential (i.e., women with functioning ovaries who have a current documented tubal ligation or hysterectomy, or women who are post-menopausal defined as no menstruation for more than 12 months);
- Child-bearing potential (i.e., women with functioning ovaries and no documented impairment of oviductal or uterine function that would cause sterility.) This category includes women with oligomenorrhoea (severe), women who are perimenopausal, and young women who have begun to menstruate. These subjects must have a negative serum pregnancy test at screening and agree to one of the following:
- Complete abstinence from intercourse from two weeks prior to administration of the first dose of study medication until 28 days after the final dose of study medication; or
- Consistent and correct use of one of the following acceptable methods of birth control:
- male partner who is sterile prior to the female subject's entry into the study and is the sole sexual partner for that female subject;
- implants of levonorgestrel;
- injectable progestogen;
- any intrauterine device (IUD) with a documented failure rate of less than 1% per year;
- oral contraceptives (either combined or progestogen only); or
- barrier methods, including diaphragm or condom with a spermicide.
- Able to swallow and retain oral medication.
- Subjects must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 1.
- Subjects may have measurable lesion(s) according to RECIST criteria as per protocol. Patients with metastases only to bone are also eligible for study enrollment.
- Subjects with stable CNS metastases or leptomeningeal involvement are eligible only if they are not taking oral steroids or enzyme-inducing anticonvulsants.
- Subjects that received prior radiotherapy must have completed radiotherapy treatment at least four weeks before enrollment and recovered from all treatment-related toxicities.
- Subjects must have a left ventricular ejection fraction (LVEF) ≥ 50% or ≥ lower limit of normal for the institution based on Multiple-gated Acquisition (MUGA) scan or echocardiogram (ECHO).
- Subjects must have adequate hematological, hepatic, and renal function.
- Hemoglobin of at least 9 gm/dL
- Absolute granulocyte count of at least 1,500/mm3 (1.5 x 109/L)
- Platelets of at least 100,000/mm3 (100 x 109/L)
- Total bilirubin not more than 2.5mg/dL
- ALT and/or AST not more than 1.5 times the upper limit of the normal range (ULN) and alkaline phosphatase not more than 2.5 times the ULN. For subjects with liver metastases, AST or ALT not more than 5 times the ULN may be enrolled if the total bilirubin is less than 1.5 times the ULN and if the ALT and AST is checked twice with an interval of at least 2 weeks prior to treatment to determine that liver function is stable.
- Calculated creatinine clearance (ClCr) of at least 50mL/min according to the formula of Cockcroft and Gault as per protocol.
- Subjects who received a taxane as part of adjuvant or neoadjuvant therapy are eligible if they had recurrence of their disease more than six months after completion of treatment. Subjects that received trastuzumab as part of adjuvant therapy are eligible if they had recurrence of their disease more than six months after completion of treatment.
- Subjects must provide signed written informed consent.
Exclusion criteria:
- Subject has peripheral neuropathy of Grade 2 or higher;
- Subject has had prior systemic cytotoxic chemotherapy for metastatic or locally recurrent disease. Also, any subjects with prior chemotherapy in the adjuvant or neoadjuvant setting with anthracycline or anthracenedione-containing regimens with cumulative doses of ≥ 360mg/m2 of doxorubicin, ≥ 720mg/m2 of epirubicin, or ≥ 72 mg/m2 of mitoxantrone. Patients with prior hormonal therapy(ies) are eligible.
- Subjects with prior systemic investigational drugs within the past 30 days or topical investigational drugs within the past seven days;
- Subjects with uncontrolled or symptomatic angina, arrhythmias.
- Subjects with Class II to IV heart failure as defined by the New York Heart Association (NYHA) functional classification system.
- Subjects with a known immediate or delayed hypersensitivity or untoward reaction to paclitaxel, trastuzumab, carboplatin, or other related compounds, or to drugs chemically related to lapatinib. These include other aminoquinazolines , such as gefitinib (Iressa), erlotinib (Tarceva), or other chemically-related compounds.
- Has malabsorption syndrome, a disease affecting gastrointestinal function, or resection of the stomach or small bowel.
- Subjects taking any prohibited medications as per protocol.
- Have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment).
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Group A
Subjects in Treatment Group A (in cohorts of three) will receive oral lapatinib QD (Days 1 to 28).
Following lapatinib administration on Day 1, paclitaxel will be administered intravenously over one hour followed immediately by an IV infusion of carboplatin over not less than 15 minutes.
Carboplatin will be followed by an initial loading dose of trastuzumab by 90 minute IV infusion (first dose only) with subsequent IV doses of trastuzumab to be given weekly over 30 minute infusion.
Doses of paclitaxel and carboplatin will be administered weekly (Day 1, 8, and 15).
Trastuzumab is administered on Day 1, 8, 15, and 22. Treatment cycles are repeated every four weeks.
|
Lapatinib (GW572016) is a potent small molecule, reversible inhibitor of both EGFR and ErbB2 tyrosine kinases
An alkylating agent used in the treatment of some cancers
A monoclonal antibody that interferes with the HER2/neu receptor
A mitotic inhibitor used in cancer treatment
|
Active Comparator: Group B
Subjects in Treatment Group B (in cohorts of three) will receive oral lapatinib QD (Days 1 to 28).
Following lapatinib administration on Day 1, paclitaxel will be administered intravenously over one hour followed immediately by a ≥15 minute intravenous infusion of carboplatin.
Doses of paclitaxel, and carboplatin will be administered weekly (Day 1, 8, and 15) for three weeks with cycles repeated every four weeks.
|
Lapatinib (GW572016) is a potent small molecule, reversible inhibitor of both EGFR and ErbB2 tyrosine kinases
An alkylating agent used in the treatment of some cancers
A mitotic inhibitor used in cancer treatment
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Adverse events and safety evaluations
Time Frame: 28 days
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28 days
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Tumor response by RECIST version 1.0
Time Frame: From date of randomization until the date of first documented progression or death from any cause,whichever came first, assessed up to 48.5 months
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Tumor response is assessed using Response Evaluation Criteria In Solid Tumors (RECIST), version 1.0. RECIST has 4 response categories:
A CR or PR should be confirmed within 4 weeks. |
From date of randomization until the date of first documented progression or death from any cause,whichever came first, assessed up to 48.5 months
|
Duration of Response (DOR)
Time Frame: From date of randomization until the date of first documented progression or death from any cause,whichever came first, assessed up to 48.5 months
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Duration of Response is defined as the time from the first documented evidence of CR or PR until the first documented sign of PD or death due to breast cancer.
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From date of randomization until the date of first documented progression or death from any cause,whichever came first, assessed up to 48.5 months
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Progression-free survival (PFS)
Time Frame: From date of randomization until the date of first documented progression or death from any cause,whichever came first, assessed up to 48.5 months
|
Progression-free survival is defined as the time from first dose until the first documented sign of disease progression or death due to any cause.
For subjects who do not progress or die, but who permanently discontinue Lapatinib treatment, progression-free survival will be censored at the time of last radiological scan preceding the initiation of alternative anti-cancer therapy.
For subjects who do not progress or die and who complete the study, progression-free survival will be censored at the time of last radiological scan preceding the date of the study conclusion.
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From date of randomization until the date of first documented progression or death from any cause,whichever came first, assessed up to 48.5 months
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
December 7, 2006
Primary Completion (Actual)
December 22, 2010
Study Completion (Actual)
September 12, 2019
Study Registration Dates
First Submitted
August 22, 2006
First Submitted That Met QC Criteria
August 22, 2006
First Posted (Estimate)
August 23, 2006
Study Record Updates
Last Update Posted (Actual)
September 9, 2020
Last Update Submitted That Met QC Criteria
September 8, 2020
Last Verified
September 1, 2020
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Skin Diseases
- Neoplasms
- Neoplasms by Site
- Breast Diseases
- Breast Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Antineoplastic Agents, Phytogenic
- Antineoplastic Agents, Immunological
- Protein Kinase Inhibitors
- Carboplatin
- Paclitaxel
- Trastuzumab
- Lapatinib
Other Study ID Numbers
- EGF103892
- CLAP016A2102 (Other Identifier: Novartis)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
No
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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