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:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00251433
First received: November 8, 2005
Last updated: December 12, 2013
Last verified: November 2013
  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
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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 GlaxoSmithKline:

Primary Outcome Measures:
  • Phase I: Optimal doses and toleration of the three drugs administered together. [ Time Frame: 3 weeks ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

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 ] [ Designated as safety issue: No ]
  • PK endpoints: Cmin and Cmax; Concentrations of alpha-1 acid glycoprotein and albumin. [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • Safety and tolerability endpoints will consist of evaluation of AEs and changes from baseline in laboratory values. [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Serum concentrations of ErbB1 and ErbB2 ECD will be correlated to tumour response. [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]

Enrollment: 53
Study Start Date: October 2005
Estimated Study Completion Date: December 2013
Primary Completion Date: June 2010 (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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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 mitoxantrome;
  • 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 anilinoquinazolines, 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00251433

Locations
United States, Tennessee
GSK Investigational Site
Nashville, Tennessee, United States, 37203
France
GSK Investigational Site
Paris Cedex 10, France, 75475
GSK Investigational Site
Paris Cedex 5, France, 75248
Ireland
GSK Investigational Site
Dublin, Ireland, 8
GSK Investigational Site
Dublin, Ireland, 4
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided by GlaxoSmithKline

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT00251433     History of Changes
Other Study ID Numbers: EGF100161
Study First Received: November 8, 2005
Last Updated: December 12, 2013
Health Authority: Ireland: Irish Medicines Board
United States: Food and Drug Administration

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

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

ClinicalTrials.gov processed this record on October 20, 2014