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GW572016 With Docetaxel and Trastuzumab for the Treatment Of Untreated ErbB2 Over-Expressing Metastatic Breast Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00251433
First Posted: November 10, 2005
Last Update Posted: June 8, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
  Purpose
This is a two-part study (Phase I/Phase II). Part I is designed to find the optimal (best) doses of GW572016, docetaxel, and trastuzumab when given together, Part II is designed to evaluate the tumor response rate (shrinkage or lack of growth) in patients receiving all three drugs compared to patients receiving only docetaxel and trastuzumab.

Condition Intervention Phase
Neoplasms, Breast Drug: lapatinib, docetaxel, trastuzumab Drug: Docetaxel, trastuzumab Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label, Multicenter, Phase I/II Dose Escalation Study of Oral GW572016 in Combination With Docetaxel (Taxotere) Plus Trastuzumab (Herceptin) in Subjects Previously Untreated for ErbB2-overexpressing Metastatic Breast Cancer

Resource links provided by NLM:


Further study details as provided by Novartis ( Novartis Pharmaceuticals ):

Primary Outcome Measures:
  • Phase I: Optimal doses and toleration of the three drugs administered together. [ Time Frame: 3 weeks ]
  • Phase II: The primary efficacy endpoint is objective tumour response rate as measured by radiological imaging, photography, and/or physical examination performed every other cycle and recorded according to RECIST criteria. [ Time Frame: 3 weeks ]

Secondary Outcome Measures:
  • Phase I and II Tumor response rate; Time to tumor response; Length of response; Time to progression of cancer; Overall survival. [ Time Frame: 6 weeks ]
  • PK endpoints: Cmin and Cmax; Concentrations of alpha-1 acid glycoprotein and albumin. [ Time Frame: 6 weeks ]
  • Safety and tolerability endpoints will consist of evaluation of AEs and changes from baseline in laboratory values. [ Time Frame: 6 weeks ]
  • Relevant biomarkers, including ErbB1, ErbB2, ErbB3, ErbB4, AKT, and potentially other biomarkers downstream from the ErbB1 and ErbB2 receptors, will be determined from tumour tissue. [ Time Frame: 6 weeks ]
  • Serum concentrations of ErbB1 and ErbB2 ECD will be correlated to tumour response. [ Time Frame: 6 weeks ]

Enrollment: 53
Actual Study Start Date: September 26, 2005
Estimated Study Completion Date: December 31, 2018
Estimated Primary Completion Date: December 31, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Phase I
The phase I part of the study will include cohorts of 3 patients to investigate doses of lapatinib (750mg, 1000mg, 1250mg, 1500mg) with 75mg/m2 3- weekly docetaxel plus standard weekly doses of trastuzumab with prophylactic use of growth factors in all patients. Further cohorts may be explored with prophylactic use of growth factors at the doses stipulated in the phase I dose escalation schema
Drug: lapatinib, docetaxel, trastuzumab
The phase I part of the study will include cohorts of 3 patients to investigate doses of lapatinib (750mg, 1000mg, 1250mg, 1500mg) with 75mg/m2 3- weekly docetaxel plus standard weekly doses of trastuzumab with prophylactic use of growth factors in all patients. Further cohorts may be explored with prophylactic use of growth factors at the doses stipulated in the phase I dose escalation schema
Other Name: GW572016
Experimental: Phase II-A
Patients will receive OTR of lapatinib, docetaxel, trastuzumab dose determined in phase I.
Drug: lapatinib, docetaxel, trastuzumab
The phase I part of the study will include cohorts of 3 patients to investigate doses of lapatinib (750mg, 1000mg, 1250mg, 1500mg) with 75mg/m2 3- weekly docetaxel plus standard weekly doses of trastuzumab with prophylactic use of growth factors in all patients. Further cohorts may be explored with prophylactic use of growth factors at the doses stipulated in the phase I dose escalation schema
Other Name: GW572016
Active Comparator: Phase II-B
Patients will receive docetaxel and trastuzumab combination.
Drug: Docetaxel, trastuzumab
For Phase II, subjects will be pre-stratified for Eastern Cooperative Oncology Group (ECOG) performance (0 vs. 1; see Appendix 4 ) and site of disease (visceral vs. non-visceral). Subjects will then be randomised in a 2:1 ratio to receive either the triplet regimen or the docetaxel and trastuzumab combination.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects must be 18 years of age.

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);
  • 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 2 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.
  • Subjects must have an ECOG Performance Status of 0 to 1.
  • Subjects must have histologically- or cytologically-confirmed invasive breast cancer with Stage IV disease.
  • Subjects must have measurable lesion(s) according to RECIST criteria for phase II, however for phase I subjects evaluable disease will be allowed (including patients with bone lesion only disease).
  • Prior to enrolment in the Phase I part of the study, subjects must have documentation of ErbB2 over-expression via IHC3+ or FISH+ testing. Prior to enrolment in the Phase II part of the study, subjects must have ErbB2 over-expression confirmed by a central laboratory,
  • Subjects with stable CNS metastases or leptomeningeal involvement are eligible only if they are not taking oral steroids or enzyme-inducing anticonvulsants. Subjects with CNS only disease will not be allowed.
  • Subjects that received prior radiotherapy must have completed radiotherapy treatment at least 4 weeks before enrolment and recovered from all treatment-related toxicities.
  • Subjects must have new or archived tumour tissue available prior to study entry to evaluate levels of relevant biomarkers.
  • Subjects must have a cardiac ejection fraction within the institutional range of normal as measured by Multigated Acquisition (MUGA) scan or echocardiogram (ECHO).
  • Subjects must have adequate haematological, hepatic, and renal function. Haemoglobin ≥9gm/dL Absolute granulocyte count ≥1500/mm³ (1.5 x 10^9/L) Platelets ≥75,000/mm³ (75 x 10^9/L) Total bilirubin ≤1.5mg/dL Both ALT and AST ≤1.5 times the upper limit of the normal range (ULN) and alkaline phosphatase ≤2.5 times the ULN (See Taxotere Data Sheet) Serum creatinine ≤ 2.0mg/dL or calculated creatinine clearance (CrCl) ≥40mL/min according to the formula of Cockcroft and Gault
  • Subjects who received a taxane as part of adjuvant or neoadjuvant therapy are eligible if they had progression of their disease more than 6 months after completion of treatment.
  • Subjects who received prior ErbB inhibitors in the adjuvant setting will be allowed, but a disease-free interval of at least 6 months must be demonstrated after the end of therapy.

Exclusion Criteria:

  • Subject has peripheral neuropathy of grade 2 or higher;
  • Subject has had prior systemic therapy (except one line of hormonal therapy) for metastatic 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 ≥72mg/m² of mitoxantrone;
  • Subjects with prior systemic investigational drugs within the past 30 days or topical investigational drugs within the past 7 days;
  • Subjects with uncontrolled or symptomatic angina, arrhythmias, or congestive heart failure;
  • Subjects with a known immediate or delayed hypersensitivity or untoward reaction to docetaxel, trastuzumab, 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.
  • Subjects taking any prohibited medications
  • Subject neither affiliated with, nor beneficiary of a social security category (For France only)
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00251433


Locations
United States, Tennessee
Novartis Investigative Site
Nashville, Tennessee, United States, 37203
France
Novartis Investigative Site
Paris Cedex 10, France, 75475
Novartis Investigative Site
Paris Cedex 5, France, 75248
Ireland
Novartis Investigative Site
Dublin, Ireland, 4
Novartis Investigative Site
Dublin, Ireland, 8
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00251433     History of Changes
Other Study ID Numbers: EGF100161
First Submitted: November 8, 2005
First Posted: November 10, 2005
Last Update Posted: June 8, 2017
Last Verified: June 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description:

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


Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Novartis ( Novartis Pharmaceuticals ):
ErbB1
ErbB2
trastuzumab (Herceptin)
lapatinib
Stage IV breast cancer
metastatic breast cancer
overexpression of ErbB2 receptors
docetaxel (Taxotere)

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Docetaxel
Lapatinib
Trastuzumab
Mitogens
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors
Enzyme Inhibitors