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HER2-positive Breast CancerPhase 2NCT01873833

Capecitabine, Cyclophosphamide, Lapatinib Ditosylate, and Trastuzumab in Treating Patients With HER2-Positive Metastatic Breast Cancer

A Phase 2 study testing capecitabine, cyclophosphamide and lapatinib ditosylate in people with HER2-positive Breast Cancer and Recurrent Breast Cancer, run by University of Southern California at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This phase II trial studies how well capecitabine, cyclophosphamide, lapatinib ditosylate, and trastuzumab work in treating patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
capecitabine, cyclophosphamide and lapatinib ditosylate
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
1 siteUnited States
Study dates
29 Jul 2013to 2 Mar 2021
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

  • Histologically confirmed HER2-positive metastatic breast cancer
  • HER2 overexpression of tumor by either immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH); tumors tested by IHC must be 3+ positive; tumors tested by FISH must have a ratio of HER2: chromosome enumeration probe (CEP)17 > 2.0; when both tests are performed, the FISH result must be positive
  • Prior trastuzumab use in the adjuvant or metastatic setting
  • No more than two prior cytotoxic chemotherapeutic regimens for metastatic breast cancer. In addition, prior Trastuzumab emtansine (TDM-1, Kadcyla) is allowed.
  • Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
  • Absolute neutrophil count (ANC) >= 1500/mm^3
Show all 17Show fewer
  • Platelets >= 100,000/mm^3
  • Hemoglobin >= 9 g/dL
  • Bilirubin =< 1.5 x upper limit of normal (ULN)
  • Serum creatinine =< 1.5 x ULN or calculated creatinine clearance >= 60 ml/min
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN
  • Fully recovered from toxicity due to prior therapy
  • Capable of understanding the informed consent and complying with the protocol and signed the informed consent document prior to any study-specific screening procedures or evaluations being performed
  • Must be able to swallow pills
  • May have either measurable or non-measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
  • Sexually active participants must agree to use a medically accepted barrier method of contraception (i.e. male condom or female condom) during the course of the study and for 3 months following discontinuation of study treatments; for participants of childbearing potential, a barrier method and a second method of contraception must be used
  • Participants of childbearing potential must have a negative pregnancy test at screening and enrollment; participants of childbearing potential are defined as premenopausal females capable of becoming pregnant, i.e. females who have had any evidence of menses in the past 12 months with the exception of those who had prior hysterectomy (oophorectomy or surgical sterilization); however, women who have been amenorrheic for >= 12 months are still considered to be of childbearing potential if the amenorrhea is possibly due to any other cause including prior chemotherapy, antiestrogens, or ovarian suppression

Who cannot join

  • Prior treatment with capecitabine or lapatinib
  • Radiation therapy within 2 weeks before the first dose of study treatment
  • Hormonal therapy within 2 weeks before the first dose of study treatment
  • Cytotoxic chemotherapy (including investigational cytotoxic chemotherapy) within 3 weeks before the first dose of study treatment
  • Biologic therapy (including antibodies [other than trastuzumab], immune modulators, cytokines) within 4 weeks before the first dose of study treatment; Note: there is no washout period required for trastuzumab
  • Any other type of investigational agent within 4 weeks before the first dose of study treatment
Show all 17Show fewer
  • Major surgery, or not recovered from major surgery within 4 weeks before the first dose of study treatment
  • Untreated, symptomatic, or progressive brain metastases; participants must have no radiographic or other signs of progression in the brain for >= 1 month after completion of local therapy; any corticosteroid use for brain metastases must have been discontinued without the subsequent appearance of symptoms for >= 4 weeks prior to first study treatment
  • Uncontrolled significant intercurrent illness that would preclude the patient from study participation per investigator assessment
  • Left ventricular ejection fraction (LVEF) =< 50% as documented by multi gated acquisition scan (MUGA) or echocardiogram performed within 28 days prior to the first study treatment
  • Currently receiving anticoagulation with therapeutic doses of warfarin (low-molecular weight heparin is permitted)
  • Pregnant or breastfeeding
  • Known to be positive for the human immunodeficiency virus (HIV) (a test for HIV at screening is not required)
  • Have acute or currently active/requiring anti-viral therapy hepatic or biliary disease (with the exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)
  • Previously identified allergy or hypersensitivity or intolerance to components of the study treatment formulation (cyclophosphamide, capecitabine, lapatinib [lapatinib ditosylate], trastuzumab)
  • Any other diagnosis of malignancy or evidence of malignancy (except non-melanoma skin cancer, in-situ carcinoma of the cervix) within 2 years prior to screening for this study
  • Unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee

Trial locations and contacts

1 site in 1 country.

United States1 site

  • USC Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

Other trials in United States

About this study

Official title: Phase II Trial of Metronomic Capecitabine and Cyclophosphamide With Lapatinib and Trastuzumab in Patients With HER2 Positive Metastatic Breast Cancer Who Have Progressed on a Previous Trastuzumab-Based Regimen

This phase II trial studies how well capecitabine, cyclophosphamide, lapatinib ditosylate, and trastuzumab work in treating patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. Drugs used in chemotherapy, such as capecitabine and cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving capecitabine and cyclophosphamide daily may kill more tumor cells. Lapatinib ditosylate may stop the growth of tumor cells by blocking some of the enzymes needed for growth. Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of the tumor to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving capecitabine, cyclophosphamide, lapatinib ditosylate, and trastuzumab together may be an effective treatment for breast cancer.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To estimate the progression free survival (PFS).

SECONDARY OBJECTIVES:

  1. To evaluate the overall response rate (ORR).

II. To evaluate the clinical benefit rate (CBR; complete response, partial response, and stable disease for >= 24 weeks).

III. To estimate the overall survival (OS).

IV. To assess the safety and tolerability.

OUTLINE:

Patients receive capecitabine orally (PO) once daily (QD), cyclophosphamide PO QD, and lapatinib ditosylate PO QD on days 1-21 and trastuzumab intravenously (IV) on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 1 year.

Being tested
capecitabine, cyclophosphamide, lapatinib ditosylate, trastuzumab, laboratory biomarker analysis
Medical subject headings
Breast Neoplasms

What participants receive

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

  • capecitabineDrug

    Also called CAPE, Ro 09-1978/000, Xeloda

    Given PO

  • cyclophosphamideDrug

    Also called CPM, CTX, Cytoxan, Endoxan

    Given PO

  • lapatinib ditosylateDrug

    Also called GSK572016, GW-572016, GW2016, Lapatinib

    Given PO

  • trastuzumabBiological

    Also called anti-c-erB-2, Herceptin, Monoclonal antibody (MOAB) HER2, MOAB HER2

    Given IV

  • laboratory biomarker analysisOther

    Correlative studies

Study groups in NCT01873833
Study groupRoleWhat they receive
Treatment (chemotherapy, lapatinib ditosylate, trastuzumab)ExperimentalPatients receive capecitabine by mouth (PO) every day (QD), cyclophosphamide PO QD, and lapatinib ditosylate PO QD on days 1-21 and trastuzumab IV on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Receives: Drug: capecitabine; Drug: cyclophosphamide; Drug: lapatinib ditosylate; Biological: trastuzumab; Other: laboratory biomarker analysis

What is being measured

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

  1. Progression Free Survival (PFS)

    PFS was defined as duration of time from the first dose of study drug to the first documentation of Progressive Disease (PD) by investigator assessment using RECIST 1.1 or death on study due to any cause on or before the data cutoff date, whichever occurred first. PD: >=20% increase (>=5 mm absolute increase) in the sum of target lesion measurements, compared to the smallest sum on study (including baseline), or unequivocal progression of non-target lesions, evaluated as a whole, such that it is clear that treatment has failed and disease is progressing, regardless of the status of the target lesions.

    Measured: From study entry to the date of first documented disease progression (assessed every 6 weeks) or death due to any cause, whichever came first, approximately 63 months.

Secondary outcomes (4)

  1. Overall Response Rate (ORR)

    Overall response rate (ORR) is complete response (CR) + partial response (PR) recorded from study entry until disease progression based on RECIST v1.1 criteria. Per RECIST 1.1 for target lesions: CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.

    Measured: From study entry until disease progression/recurrence (maximum duration: 351 weeks)

  2. Clinical Benefit Rate (CBR)

    Participants with a best response of CR, PR, or stable disease (SD) sustained for ≥24 weeks, as assessed using RECIST v1.1. CR: Disappearance of all non-nodal target and non-target lesions, including target and non-target lymph nodes reduction to <10 mm in short axis. PR: >=30% decrease in sum of diameters of target lesions, compared to the sum at baseline. SD: Neither PR nor progression of disease (PD) criteria met. SD follow PR only when sum increases by less than 20% from the nadir, but previously seen 30% decrease from baseline no longer hold. PD: >=20% increase (>=5 mm absolute increase) in the sum of target lesion measurements, compared to the smallest sum on study (including baseline), or unequivocal progression of non-target lesions, evaluated as a whole, such that it is clear that treatment has failed and disease is progressing, regardless of the status of the target lesions.

    Measured: From study entry until the date of the first documented disease progression of date of death whichever came first, assessed for approximately 351 weeks

  3. Overall Survival (OS)

    OS is the duration from study entry to death. Participants last known to be alive are censored at date of last contact.

    Measured: From study entry until death from any cause or date of last contact (up to 70 months)

  4. Number of Participants With Any Adverse Events as a Measure of Safety and Tolerability

    Assessment based on CTCAE version 4.0 toxicity criteria. For the detailed list of adverse events see the adverse event module.

    Measured: ****Time Frame: Adverse events were collected from first dose of study treatment up to 30 days after last dose of treatment, up to 63 months (number or treatment given ranged from 2 cycles to 85 cycles).

Timeline

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

  1. First posted10 Jun 2013 (estimated)
  2. Study start29 Jul 2013
  3. Primary completion2 Mar 2021
  4. Study completion2 Mar 2021

Why it stopped: Insufficient accrual

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
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01873833
Sponsor's protocol ID
1B-12-10
Other IDs
NCI-2013-01086, P30CA014089
Status last verified
Sep 2023
First submitted
6 Jun 2013
Last updated
5 Oct 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing capecitabine, cyclophosphamide and lapatinib ditosylate in people with HER2-positive Breast Cancer and Recurrent Breast Cancer, run by University of Southern California at 1 site 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 17 inclusion and 17 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: stopped early, as of the sponsor's last update on 5 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 5 Oct 2023). 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?

Progression Free Survival (PFS) (time frame: From study entry to the date of first documented disease progression (assessed every 6 weeks) or death due to any cause, whichever came first, approximately 63 months.). 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 NCT01873833.

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 5 Oct 2023.

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