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

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ClinicalTrials.gov Identifier: NCT00251433
Recruitment Status : Active, not recruiting
First Posted : November 10, 2005
Last Update Posted : June 27, 2018
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Tracking Information
First Submitted Date  ICMJE November 8, 2005
First Posted Date  ICMJE November 10, 2005
Last Update Posted Date June 27, 2018
Actual Study Start Date  ICMJE September 26, 2005
Actual Primary Completion Date June 10, 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 7, 2013)
  • 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 ]
Original Primary Outcome Measures  ICMJE
 (submitted: November 9, 2005)
Phase I: Optimal doses and toleration of the three drugs administered together Phase II: Tumor progression measured by radiological imaging 6 weekly
Change History Complete list of historical versions of study NCT00251433 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: November 7, 2013)
  • 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: November 9, 2005)
Phase I and II Tumor response rate Time to tumor response Length of response Time to progression of cancer Overall survival Phase II specific biomarkers in tumor tissue
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE GW572016 With Docetaxel and Trastuzumab for the Treatment Of Untreated ErbB2 Over-Expressing Metastatic Breast Cancer
Official Title  ICMJE 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
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Neoplasms, Breast
Intervention  ICMJE
  • 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
  • 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.
Study Arms
  • 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
    Intervention: Drug: lapatinib, docetaxel, trastuzumab
  • Experimental: Phase II-A
    Patients will receive OTR of lapatinib, docetaxel, trastuzumab dose determined in phase I.
    Intervention: Drug: lapatinib, docetaxel, trastuzumab
  • Active Comparator: Phase II-B
    Patients will receive docetaxel and trastuzumab combination.
    Intervention: Drug: Docetaxel, trastuzumab
Publications * Crown J, Kennedy MJ, Tresca P, Marty M, Espie M, Burris HA, DeSilvio M, Lau MR, Kothari D, Koch KM, Diéras V. Optimally tolerated dose of lapatinib in combination with docetaxel plus trastuzumab in first-line treatment of HER2-positive metastatic breast cancer. Ann Oncol. 2013 Aug;24(8):2005-11. doi: 10.1093/annonc/mdt222.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: November 4, 2010)
53
Original Enrollment  ICMJE
 (submitted: November 9, 2005)
180
Estimated Study Completion Date December 31, 2019
Actual Primary Completion Date June 10, 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France,   Ireland,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00251433
Other Study ID Numbers  ICMJE EGF100161
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
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

Responsible Party Novartis ( Novartis Pharmaceuticals )
Study Sponsor  ICMJE Novartis Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
PRS Account Novartis
Verification Date June 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP