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

NCT01873833 | Terminated Phase 2 Results DMC FDA Drug

• 3 other identifiers: 1B-12-10NCI-2013-01086P30CA014089
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

HER2-positive Breast Cancer; Recurrent Breast Cancer; Stage IV Breast Cancer

Outcome Measures

Primary Outcomes (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.

  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)

• Overall Response Rate (ORR)

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

• Clinical Benefit Rate (CBR)

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

• Overall Survival (OS)

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

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

  ****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).

Study Arms (1)

Treatment (chemotherapy, lapatinib ditosylate, trastuzumab)

EXPERIMENTAL

Patients 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.

Drug: capecitabine; Drug: cyclophosphamide; Drug: lapatinib ditosylate; Biological: trastuzumab; Other: laboratory biomarker analysis

Interventions

capecitabine DRUG

Given PO

Also known as: CAPE, Ro 09-1978/000, Xeloda

Treatment (chemotherapy, lapatinib ditosylate, trastuzumab)

cyclophosphamide DRUG

Given PO

Also known as: CPM, CTX, Cytoxan, Endoxan, Endoxana

Treatment (chemotherapy, lapatinib ditosylate, trastuzumab)

lapatinib ditosylate DRUG

Given PO

Also known as: GSK572016, GW-572016, GW2016, Lapatinib, Tykerb

Treatment (chemotherapy, lapatinib ditosylate, trastuzumab)

trastuzumab BIOLOGICAL

Given IV

Also known as: anti-c-erB-2, Herceptin, Monoclonal antibody (MOAB) HER2, MOAB HER2

Treatment (chemotherapy, lapatinib ditosylate, trastuzumab)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (chemotherapy, lapatinib ditosylate, trastuzumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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)

Sponsors & Collaborators

• University of Southern California: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Capecitabine; Cyclophosphamide; Lapatinib; N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl-6-(5-((methylsulfonyl)ethyl)aminomethyl)-2-furyl)-4-quinazolinamine; Trastuzumab; Antibodies, Monoclonal

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Fluorouracil; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Antibodies, Monoclonal, Humanized; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Victoria Soto, Regulatory Administrator
• Organization: USC Norris Comprehensive Cancer Center

Victoria.Soto@med.usc.edu

323-865-0432

Study Officials

• Darcy V Spicer, MD

  University of Southern California

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 6, 2013
• First Posted: June 10, 2013
• Study Start: July 29, 2013
• Primary Completion: March 2, 2021
• Study Completion: March 2, 2021
• Last Updated: October 5, 2023
• Results First Posted: October 5, 2023

Record last verified: 2023-09

Locations

US (1)