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

Novartis Pharmaceuticals1 site in 1 country53 target enrollmentSeptember 26, 2005

ConditionsNeoplasms, Breast

Interventionslapatinib, docetaxel, trastuzumab

Drugslapatinib, docetaxel, trastuzumab

Overview

Phase: Phase 1
Intervention: lapatinib, docetaxel, trastuzumab
Conditions: Neoplasms, Breast
Sponsor: Novartis Pharmaceuticals
Enrollment: 53
Locations: 1
Primary Endpoint: Phase I: Optimal doses and toleration of the three drugs administered together.
Status: Terminated
Last Updated: 3 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This study was designed to be two-part study (Phase I/Phase II). Part I was designed to find the optimal (best) doses of GW572016, docetaxel, and trastuzumab when given together. Part II was 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

Phase II part was cancelled before it started. Participants were only enrolled in the phase I part and NOT the phase II part.

Registry

clinicaltrials.gov

Start Date

September 26, 2005

End Date

June 22, 2022

Last Updated

3 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Novartis Pharmaceuticals

Responsible Party

Sponsor

Eligibility 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
•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).

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)

Arms & Interventions

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: lapatinib, docetaxel, trastuzumab

Outcomes

Primary Outcomes

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 Outcomes

Phase I and II Tumor response rate; Time to tumor response; Length of response; Time to progression of cancer; Overall survival.(6 weeks)
PK endpoints: Cmin and Cmax; Concentrations of alpha-1 acid glycoprotein and albumin.(6 weeks)
Safety and tolerability endpoints will consist of evaluation of AEs and changes from baseline in laboratory values.(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.(6 weeks)
Serum concentrations of ErbB1 and ErbB2 ECD will be correlated to tumour response.(6 weeks)