Neoplasms, BreastPhase 1NCT00367471
Combination Of Lapatinib With Carboplatin, Paclitaxel, and With or Without Trastuzumab In Metastatic Breast Cancer.
A Phase 1 study testing lapatinib, carboplatin and trastuzumab in people with Neoplasms, Breast, run by Novartis Pharmaceuticals at 3 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasms, Breast
- What is being tested?
- lapatinib, carboplatin and trastuzumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 3 sitesUnited States
- Study dates
- 7 Dec 2006to 12 Sep 2019
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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.
Who cannot join
- 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.
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- 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).
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Novartis Investigative Site
Greensboro, North Carolina, 27403
Novartis Investigative Site
Indianapolis, Indiana, 46202
Novartis Investigative Site
La Jolla, California, 92093-0987
About this study
Official title: 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.
- Conditions
- Neoplasms, Breast
- Being tested
- lapatinib, carboplatin, trastuzumab, paclitaxel
- Keywords
- metastatic, paclitaxel, lapatinib, trastuzumab, carboplatin, breast cancer
- Medical subject headings
- Breast Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
lapatinibDrug
Lapatinib (GW572016) is a potent small molecule, reversible inhibitor of both EGFR and ErbB2 tyrosine kinases
carboplatinDrug
An alkylating agent used in the treatment of some cancers
trastuzumabDrug
A monoclonal antibody that interferes with the HER2/neu receptor
paclitaxelDrug
A mitotic inhibitor used in cancer treatment
| Study group | Role | What they receive |
|---|---|---|
| Group A | Active comparator | 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. Receives: Drug: lapatinib; Drug: carboplatin; Drug: trastuzumab; Drug: paclitaxel |
| Group B | Active comparator | 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. Receives: Drug: lapatinib; Drug: carboplatin; Drug: paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse events and safety evaluations
- The OTR for Treatment Group A (lapatinib, paclitaxel, carboplatin, and trastuzumab) will be defined as the maximum dose level at which no more than one subject out of six experiences a dose-limiting toxicity (DLT) after completing one treatment cycle.
- The OTR for Treatment Group B (lapatinib, paclitaxel, carboplatin) will be defined as the maximum dose level at which no more than one subject out of six experiences a DLT after completing one treatment cycle.
- Adverse events and changes from baseline in laboratory values, Multiple-gated Acquisition (MUGA) scanning/Echocardiogram (ECHO), and vital signs will be evaluated to assess safety and tolerability.
Measured: 28 days
Secondary outcomes (3)
Tumor response by RECIST version 1.0
Tumor response is assessed using Response Evaluation Criteria In Solid Tumors (RECIST), version 1.0. RECIST has 4 response categories:
- Complete Response (CR) = disappearance of all target and non-target lesions.
- Partial Response (PR) = at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of diameters.
- Progressive Disease (PD) = At least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline.
- Stable Disease (SD) = neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD.
A CR or PR should be confirmed within 4 weeks.
Measured: 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)
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.
Measured: 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 (PFS)
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.
Measured: 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
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Aug 2006 (estimated)
- Study start7 Dec 2006
- Primary completion22 Dec 2010
- Study completion12 Sep 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neoplasms, BreastStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00367471
- Sponsor's protocol ID
- EGF103892
- Other IDs
- CLAP016A2102
- Status last verified
- Sep 2020
- First submitted
- 22 Aug 2006
- Last updated
- 9 Sep 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT00367471
- Acronym / sponsor ID
- EGF103892
- Conditions
- Neoplasms, Breast
- Keywords
- metastatic, paclitaxel, lapatinib, trastuzumab, carboplatin, breast cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 7 Dec 2006 (actual)
- Primary completion
- 22 Dec 2010 (actual)
- Study completion
- 12 Sep 2019 (actual)
- First posted
- 23 Aug 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group A | Active comparator | Drug: lapatinib, Drug: carboplatin, Drug: trastuzumab, Drug: paclitaxelSubjects 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. |
| Group B | Active comparator | Drug: lapatinib, Drug: carboplatin, Drug: paclitaxelSubjects 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (31 listed)
- 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
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| lapatinibLapatinib (GW572016) is a potent small molecule, reversible inhibitor of both EGFR and ErbB2 tyrosine kinases | Drug | Group A, Group B |
| carboplatinAn alkylating agent used in the treatment of some cancers | Drug | Group A, Group B |
| trastuzumabA monoclonal antibody that interferes with the HER2/neu receptor | Drug | Group A |
| paclitaxelA mitotic inhibitor used in cancer treatment | Drug | Group A, Group B |
Primary outcome
Adverse events and safety evaluations
Time frame: 28 days
* The OTR for Treatment Group A (lapatinib, paclitaxel, carboplatin, and trastuzumab) will be defined as the maximum dose level at which no more than one subject out of six experiences a dose-limiting toxicity (DLT) after completing one treatment cycle. * The OTR for Treatment Group B (lapatinib, paclitaxel, carboplatin) will be defined as the maximum dose level at which no more than one subject out of six experiences a DLT after completing one treatment cycle. * Adverse events and changes from baseline in laboratory values, Multiple-gated Acquisition (MUGA) scanning/Echocardiogram (ECHO), and vital signs will be evaluated to assess safety and tolerability.
3 secondary outcomes
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
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
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2020.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing lapatinib, carboplatin and trastuzumab in people with Neoplasms, Breast, run by Novartis Pharmaceuticals at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 31 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse events and safety evaluations (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Sep 2020.