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Neoplasms, BreastPhase 2NCT00709761

Phase II Lapatinib Plus Nab-Paclitaxel As First And Second Line Therapy In her2+ MBC

A Phase 2 study testing Lapatinib/nab-Paclitaxel in people with Neoplasms, Breast, run by Novartis Pharmaceuticals at 13 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This was an open-label, single-arm, multi-center, Phase II study to determine the activity of nab-paclitaxel plus lapatinib in the first and second-line setting in women with ErbB2 overexpressing metastatic breast cancer (MBC). Sixty subjects were to be enrolled in the study. Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Neoplasms, Breast
What is being tested?
Lapatinib/nab-Paclitaxel
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
13 sitesUnited States
Study dates
2 Jul 2008to 3 Jan 2018
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • A subject was eligible for inclusion in this study only if all of the following criteria apply:
  • Subjects must have histologically confirmed invasive breast cancer with Stage IV disease at primary diagnosis or at relapse after curative-intent surgery. Where the disease was restricted to a solitary lesion, the neoplastic nature of the lesion should have been confirmed by cytology or histology.
  • Documented amplification of ErbB2 3+ by immunohistochemistry or a positive score (>2.2) by FISH using a local laboratory result (which was considered sufficient in this study with no further verification by a central laboratory).
  • Subjects must have received no more than one prior chemotherapeutic regimen in the metastatic setting.
  • If a taxane had been administered in the neoadjuvant, adjuvant or metastatic setting, progression must have occurred ≥12 months after completion of this treatment.
  • Prior therapy with radiation for this breast cancer population was permitted if it was administered in the neoadjuvant or adjuvant non metastatic setting. Radiotherapy given in the metastatic setting, prior to initiation of study medication, was allowed to a limited area (e.g., palliative therapy and involving less than 25% of bone marrow), if it was not the sole site of disease. Subjects must have completed radiation treatment and recovered from all acute radiation treatment related toxicities (e.g., bone marrow suppression) prior to commencement of combination treatment.
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  • The subject must have received all prior chemotherapy treatment at least 4 weeks prior to enrollment in this study and must have recovered from all related toxicities. Subjects who have received weekly dose of prior chemotherapy e.g. gemcitabine or capecitabine may enroll 2 to 3 weeks after cessation of treatment provided that they have recovered from all related toxicities.
  • Prior therapy with trastuzumab in the neoadjuvant, adjuvant or metastatic setting was permitted. The subject must have received all prior trastuzumab treatment at least 4 weeks prior to enrollment in this study and must have recovered from all related toxicities.
  • Prior endocrine therapy was permitted in the neoadjuvant or adjuvant or metastatic setting. The subject must have received all prior endocrine treatment at least 1 week prior to enrollment in this study and must have recovered from all related toxicities.
  • Prior diagnosis of cancer was allowed as long as the subject was free of disease for 5 years. Subjects with completely resected basal or squamous cell skin cancer, thyroid cancer or successfully treated cervical carcinoma in-situ were allowed if it had been 1 year or greater since definitive surgery.
  • Subjects must have had measurable disease, according to Response Evaluation Criteria in Solid Tumors (RECIST) guidelines; defined as at least 1 lesion that can be accurately measured in at least 1 dimension (longest diameter [LD] to be recorded) by mammogram, ultrasound or physical exam [Therasse, 2000].
  • Subjects with liver metastases or stable chronic liver disease were permitted into the study.
  • Women ≥18 years of age:
  • Non-child-bearing potential (i.e., women with functioning ovaries who had a current documented tubal ligation or hysterectomy, or women who were postmenopausal); or
  • Child-bearing potential (i.e., women with functioning ovaries and no documented impairment of oviductal or uterine function that would cause sterility). This category included women with oligomenorrhoea (severe), women who were perimenopausal and young women who had begun to menstruate. These subjects must provided a negative serum pregnancy test at Screening and agree to 1 of the following:
  • Complete abstinence from intercourse from 2 weeks prior to administration of the first dose of study medication until 5 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 was sterile prior to the female subject's entry into the study and was the sole sexual partner for that female subject.
  • Implants of levonorgestrel.
  • Injectable progestogen.
  • Any intrauterine device with a documented failure rate of less than 1% per year.
  • Oral contraceptives (either combined or progestogen only).
  • Barrier methods, including diaphragm or condom with a spermicide.
  • Considered by the Investigator to have a life expectancy of ≥6 months.
  • ECOG Performance Status (PS) of 0 or 1 (Karnofsky ≥80%) [Oken, 1982].
  • Subjects must have had normal organ and marrow function as below:
  • Hematologic
  • Absolute neutrophil count ≥1.5 × 10^9/L
  • Hemoglobin ≥9 g/dL
  • Platelets ≥100 × 10^9/L
  • Hepatic
  • Serum bilirubin ≤ upper limit of normal (ULN)
  • Aspartate aminotransferase ≤3 × ULN without liver metastases and alanine aminotransferase ≤5 × ULN if documented liver metastases
  • Renal
  • Serum creatinine ≤1.5 mg/dL
  • OR -
  • Calculated creatinine clearance ≥40 mL/min
  • Subjects must have had a cardiac ejection fraction of >50% as measured by echocardiogram (ECHO) or multigated acquisition scan (MUGA) and within the institutional range of normal.
  • Subjects with stable central nervous system metastases (stable for at least 3 months) as confirmed by computerized tomography (CT)/magnetic resonance imaging (MRI) or evidence of leptomeningeal involvement were eligible only if they were not taking steroids or enzyme-inducing anticonvulsants.
  • Subject must have been free of gastrointestinal diseases that impede swallowing and retaining of oral medications.
  • Signed, informed consent prior to registration.
  • Bisphosphonate therapy for bone metastases was allowed; however, treatment must be initiated prior to the first dose of study medication. Prophylactic use of bisphosphonates in subjects without bone disease, except for the treatment of osteoporosis, was not permitted.
  • Subjects whose disease was estrogen receptor + and/or progesterone receptor + or unknown status were included in the study if they met the following criteria:
  • They had symptomatic visceral disease that required chemotherapy.
  • Significant visceral organ tumor burden
  • The disease was considered by the Investigator to be progressing rapidly or life threatening.
  • Subjects who have received prior endocrine therapy and who were no longer benefiting from this therapy.

Who cannot join

  • A subject was not be eligible for inclusion in this study if any of the following criteria apply:
  • Subjects who received more than one prior chemotherapeutic regimen in the metastatic setting
  • Subjects taking treatment with medications provided in the list of restricted medications and substances in the drug information section for lapatinib were not eligible for the study. This included human immunodeficiency virus-positive subjects receiving combination anti-retroviral therapy because of possible pharmacokinetic interactions with lapatinib.
  • Prior treatment with lapatinib.
  • Concurrent anticancer or concomitant radiotherapy treatment;
  • Concurrent treatment with prohibited medications;
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  • Use of an investigational drug within 30 days or 5 half-lives, whichever was longer, preceding the first dose of investigational treatment, or, concurrent treatment with an investigational agent or participation in another clinical trial involving investigational agents.
  • Known history of allergic reactions attributed to compounds of similar chemical or biologic composition to lapatinib or nab-paclitaxel or excipients;
  • Known history of uncontrolled inter-current illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, clinically significant cardiac arrhythmia, or psychiatric illness/social situations that would have limited compliance with study requirements.
  • Had 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)
  • Concurrent disease or condition that would make the subject inappropriate for study participation or any serious medical disorder that would interfere with the subject's safety.
  • Pregnant or lactating females at any time during the study (due to the potential teratogenic or abortifacient effects of lapatinib and breastfeeding).
  • Subjects with diseases affecting gastrointestinal function resulting in an inability to take oral medication, including; malabsorption syndrome, a requirement for iv alimentation, prior surgical procedures affecting absorption e.g. gastric resection and uncontrolled inflammatory bowel disease (e.g., Crohn's, ulcerative colitis).
  • Peripheral neuropathy of Grade 2 or greater.
  • Unresolved or unstable, serious toxicity from prior administration of another investigational drug and/or of prior cancer treatment.
  • History of prior malignancy. However, subjects who had been disease-free for 5 years, or subjects with completely resected basal or squamous cell skin cancer, thyroid cancer or successfully treated cervical carcinoma in situ were eligible if it had been at least 1 year since definitive surgery.
  • or rendering of informed consent.
  • Other Eligibility Criteria Considerations:
  • To assess any potential impact on subject eligibility with regard to safety, the Investigator must refer to the following document(s) for detailed information regarding warnings, precautions, contraindications, AEs, and other significant data pertaining to the investigational product(s) being used in this study: Clinical Investigator's Brochure (IB), SPM, and the nab-paclitaxel Product Label.

Trial locations and contacts

13 sites in 1 country.

13 sites in 1 country

United States13 sites

  • Novartis Investigative Site

    Atlanta, Georgia, 30341

  • Novartis Investigative Site

    Cincinnati, Ohio, 45242

  • Novartis Investigative Site

    Cleveland, Ohio, 44106

  • Novartis Investigative Site

    Everett, Washington, 98201

  • Novartis Investigative Site

    Fort Myers, Florida, 33916

  • Novartis Investigative Site

    La Verne, California, 91750

  • Novartis Investigative Site

    Long Beach, California, 90813

  • Novartis Investigative Site

    Nashville, Tennessee, 37203

  • Novartis Investigative Site

    New York, New York, 10065

  • Novartis Investigative Site

    Richmond, Virginia, 23230

  • Novartis Investigative Site

    Rochester, New York, 14623

  • Novartis Investigative Site

    Salem, Virginia, 24153

  • Novartis Investigative Site

    Tacoma, Washington, 98405

Other trials in United States

About this study

Official title: LPT 111111- A Single-arm, Multicenter Phase II Study to Evaluate The Combination of Weekly Nanoparticle Albumin Bound Paclitaxel (Nab-Paclitaxel or ABRAXANE®) and Lapatinib (TYKERB®) in Women With No More Than One Prior Treatment for ErbB2 Overexpressing Metastatic Breast Cancer

This was an open-label, single-arm, multi-center, Phase II study to determine the activity of nab-paclitaxel plus lapatinib in the first and second-line setting in women with ErbB2 overexpressing metastatic breast cancer (MBC). Sixty subjects were to be enrolled in the study. Subjects were to receive nab-paclitaxel (100 mg/m2 intravenously once weekly for 3 weeks, followed by a rest week in a 4-week cycle) plus lapatinib (1000 mg once daily). Subjects were to receive treatment until disease progression or withdrawal from the study. The primary objective of this study was to evaluate overall tumor response rate of lapatinib in combination with nab-paclitaxel administered in women with ErbB2 overexpressing MBC who received no chemotherapeutic regimen in the metastatic setting. Secondary objectives included progression-free survival, overall survival, duration of response, time to response and time to progression and safety. Safety and efficacy assessments were to be performed at 8 and 12 week intervals, and at the end of treatment.

Subject: Metastatic Breast Cancer, ErbB2, First-line therapy, Lapatinib, Nab-paclitaxel

Being tested
Lapatinib/nab-Paclitaxel
Keywords
Erbb2, ABRAXANE, MBC, first or second line therapy, Metastatic Breast Cancer, TYKERB
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Lapatinib/nab-PaclitaxelDrug

    This was an open-label, single-arm, multi-center, Phase II study to determine the activity of nab-paclitaxel plus lapatinib (TYKERB) in the first and second-line setting in women with ErbB2 overexpressing metastatic breast cancer (MBC). Subjects were to receive nab-paclitaxel (100 mg/m2 intravenously on Day 1, 8, 15, every 28 days (q28) days plus lapatinib (1000 mg once daily on a continuous basis).

Study groups in NCT00709761
Study groupRoleWhat they receive
Single ArmExperimentalSingle arm combination therapy of Lap and NabPaclitaxel combination
Receives: Drug: Lapatinib/nab-Paclitaxel

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Tumor Response (OR)

    OR was defined as the percentage of participants experiencing either a confirmed complete response (CR) or a confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria 1.0. CR is defined as the disappearance of all lesions (target and/or non-target). PR is defined as at least a 30% decrease in the sum of the longest dimensions (LD) of target lesions taking as a reference the baseline sum LD, with non-target lesions not increased or absent.

    Measured: Start of treatment to disease progression or death or discontinuation from study or at least 28 days after last dose (up to Week 131)

Secondary outcomes (5)

  1. Overall Survival (OS)

    OS was defined as the time from the start of treatment until death due to any cause. For participants who did not die, time to death was censored at the time of last contact. OS could not be analyzed because only 13 participants had died as of data cut off, and data were not mature (greater than 75% of the participants were censored for the endpoint).

    Measured: Start of treatment to death (up to Week 131)

  2. Duration of Response (DOR)

    DOR was defined for the subset of participants who showed a confirmed CR or PR, as the time from first documented evidence of CR or PR until the first documented sign of disease progression or death.

    Measured: First documented response (CR or PR) to disease progression or death (up to Week 131)

  3. Time to Response (TTR)

    TTR was defined for the subset of participants who showed a confirmed CR or PR, as the time from the start of treatment until the first documented evidence of CR or PR (whichever status was recorded first).

    Measured: Start of treatment to first documented response (CR or PR) (up to Week 131)

  4. Time to Progression (TTP)

    TTP was defined as the interval between the start of treatment until the earliest date of disease progression or death due to breast cancer.

    Measured: Start of treatment to disease progression or death (up to Week 131)

  5. Progression-Free Survival (PFS)

    PFS was defined as the time from the start of treatment until the earliest date of disease progression or death due to any cause, if sooner.

    Measured: Start of treatment to disease progression or death (up to Week 131)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Jul 2008 (estimated)
  2. Study start2 Jul 2008
  3. Primary completion5 Jan 2011
  4. Study completion3 Jan 2018

Resources

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 2
Primary purpose
Treatment
Masking
None (open label)
Enrolment
60 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00709761
Sponsor's protocol ID
LPT111111
Status last verified
Mar 2019
First submitted
1 Jul 2008
Last updated
26 Mar 2019
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Publications

  • Yardley DA, Hart L, Bosserman L, Salleh MN, Waterhouse DM, Hagan MK, Richards P, DeSilvio ML, Mahoney JM, Nagarwala Y. Phase II study evaluating lapatinib in combination with nab-paclitaxel in HER2-overexpressing metastatic breast cancer patients who have received no more than one prior chemotherapeutic regimen. Breast Cancer Res Treat. 2013 Jan;137(2):457-64. doi: 10.1007/s10549-012-2341-9. Epub 2012 Dec 8.

    PubMed 23224144

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Lapatinib/nab-Paclitaxel in people with Neoplasms, Breast, run by Novartis Pharmaceuticals at 13 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 47 inclusion and 19 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 26 Mar 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Nov 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Overall Tumor Response (OR) (time frame: Start of treatment to disease progression or death or discontinuation from study or at least 28 days after last dose (up to Week 131)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00709761, which also lists 1 linked publication.

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 26 Mar 2019.

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