A Study of Herceptin (Trastuzumab) in Women With Metastatic Breast Cancer

Phase 2

Completed

• Conditions: Breast Cancer
• Interventions: Drug: Trastuzumab; Drug: Taxane (docetaxel or paclitaxel)

• Registration Number: NCT00475670
• Lead Sponsor: Hoffmann-La Roche

Brief Summary

This 2 arm study will assess the efficacy and safety of intravenous Herceptin with or without a taxane for the first line treatment of metastatic breast cancer in women who have relapsed at least 12 months after a minimum of 10 months of (neo)adjuvant treatment with Herceptin for HER2-positive early breast cancer.Patients will receive either Herceptin monotherapy (loading dose of 4mg/kg iv, followed by weekly doses of 2mg/kg iv, or 8mg/kg loading dose followed by 3-weekly doses of 6mg/kg)or Herceptin + a taxane (docetaxel 100mg/m2 iv every 3 weeks, or paclitaxel 175mg/m2 iv every 3 weeks or 75mg/m2 every week). The anticipated time on study treatment is until disease progression, and the target sample size is \<100 individuals.

Detailed Description

Not available

Study Timeline

• Study Start: 2005-10
• Study First Submitted: 2007-05-17
• Study First Submitted QC: 2007-05-17
• Study First Posted: 2007-05-21
• Primary Completion: 2012-06
• Study Completion: 2012-06
• Results First Submitted: 2014-07-15
• Status Verified: 2014-09
• Results First Submitted QC: 2014-09-09
• Last Update Submitted: 2014-09-09
• Results First Posted: 2014-09-15
• Last Update Posted: 2014-09-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 44

Inclusion Criteria

• at least 10 months of Herceptin treatment for HER2-positive early breast cancer;
• metastatic breast cancer >=12 months after discontinuation of Herceptin;
• measurable disease.

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Exclusion Criteria

• previous chemotherapy for metastatic breast cancer;
• brain metastases;
• invasive malignancy other than metastatic breast cancer.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Trastuzumab, Taxane	Taxane (docetaxel or paclitaxel)	Participant received an initial loading dose of 4 mg/kg trastuzumab i.v. on Day 1, followed by 2mg/kg i.v. weekly, or an initial loading dose of 8 mg/kg i.v. loading dose, followed by 6 mg/kg i.v. every 3 weeks, until disease progression, unacceptable toxicity, withdrawal or death; and concomitant taxane, which is either 100 milligrams per square meter (mg/m2) docetaxel i.v. every 3 weeks, or 75 mg/m2 weekly or 175 mg/m2 every 3 weeks paclitaxel for at least 18 weeks, or more at the discretion of the investigator.
Trastuzumab Monotherapy	Trastuzumab	Participants received an initial loading dose of 4 milligrams per kilogram (mg/kg) trastuzumab intravenous (i.v.) on Day 1, followed by 2mg/kg i.v. weekly, or an initial loading dose of 8 mg/kg i.v. loading dose on Day 1, followed by 6 mg/kg i.v. every 3 weeks, until disease progression, unacceptable toxicity, withdrawal or death.
Trastuzumab, Taxane	Trastuzumab	Participant received an initial loading dose of 4 mg/kg trastuzumab i.v. on Day 1, followed by 2mg/kg i.v. weekly, or an initial loading dose of 8 mg/kg i.v. loading dose, followed by 6 mg/kg i.v. every 3 weeks, until disease progression, unacceptable toxicity, withdrawal or death; and concomitant taxane, which is either 100 milligrams per square meter (mg/m2) docetaxel i.v. every 3 weeks, or 75 mg/m2 weekly or 175 mg/m2 every 3 weeks paclitaxel for at least 18 weeks, or more at the discretion of the investigator.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR) According to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.0 Guidelines	Baseline (BL); Day 1 of Weeks 7, 13, 19, 25, 37, and 52, at the last administration of study treatment, every 24 weeks thereafter until disease progression for up to 6 months after the last participant was recruited	CR was defined for target lesions (TLs) as the disappearance of all lesions, and for nontarget lesions (NTLs) as the disappearance of all nontarget nonmeasurable lesions. PR was defined for TLs as at least a 30 percent (%) decrease from baseline (BL) in the sum of longest diameter (SLD) of TLs. 95% confidence interval for one-sample binomial using Pearson-Clopper method.

Secondary Outcome Measures

Name	Time	Method
Duration of Response - Percentage of Participants With Progressive Disease or Death	BL, Day 1 of Weeks 7, 13, 19, 25, 37, and 52, at the last administration of study treatment, every 24 weeks thereafter until disease progression for up to 6 months after the last participant was recruited	Duration of response was defined as the time from first confirmed CR or PR until death or progressive disease (PD). For TLs, PD was defined as at least a 20% increase in the SLD of the TL, taking as reference the smallest SLD recorded since the beginning of treatment or the appearance of one or more new lesions. For NTLs, PD was defined as the appearance of one or more new lesions or unequivocal progression of existing non target non-measurable lesions. Participants were censored at the date of the last tumor assessment.
Duration of Response	BL, Day 1 of Weeks 7, 13, 19, 25, 37, and 52, at the last administration of study treatment, every 24 weeks thereafter until disease progression for up to 6 months after the last participant was recruited	The time, in months, from when the response (CR or PR) was first noted until the date of documented PD, death, or withdrawal, whichever occurred first. Participants were censored at the date of the last tumor assessment.
Progression-free Survival (PFS) - Percentage of Participants With Progressive Disease	BL, Day 1 of Weeks 7, 13, 19, 25, 37, and 52, at the last administration of study treatment, every 24 weeks thereafter until disease progression for up to 6 months after the last participant was recruited	PFS was defined as the time from day of first study drug infusion until death or PD. Participants were censored at the date of the last tumor assessment.
Progression-Free Survival	BL, Day 1 of Weeks 7, 13, 19, 25, 37, and 52, at the last administration of study treatment, every 24 weeks thereafter until disease progression for up to 6 months after the last participant was recruited	The time, in months, from BL to PFS event.
Percentage of Participants With Treatment Failure	BL, Day 1 of Weeks 7, 13, 19, 25, 37, and 52, at the last administration of study treatment, every 24 weeks thereafter until disease progression for up to 6 months after the last participant was recruited	Treatment failure was defined as the time from first study drug infusion to failure. Failure was defined as any of the following: PD, death, withdrawal due to adverse event (AE) or lab abnormality, or refusal of treatment. Participants were censored at the last date recorded in the case report form (CRF) or the date of withdrawal.
Time to Treatment Failure	BL, Day 1 of Weeks 7, 13, 19, 25, 37, and 52, at the last administration of study treatment, every 24 weeks thereafter until disease progression for up to 6 months after the last participant was recruited	The time, in months, from BL to treatment failure.
Percentage of Participants With Clinical Benefit According to RECIST Guidelines	BL, Day 1 of Weeks 7, 13, 19, 25, 37, and 52, at the last administration of study treatment, every 24 weeks thereafter until disease progression for up to 6 months after the last participant was recruited	Clinical benefit was defined as stable disease (SD) for 6 months or longer, or a confirmed overall response of CR or PR. For TLs, SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest SLD since the beginning of treatment. For NTLs, SD was synonymous with incomplete response and defined as the persistence of one or more NTLs and/or maintenance of tumor marker level above the normal limits.
Overall Survival - Percentage of Participants Who Died	BL, Day 1 of Weeks 1, 4, 7, 10, 13, 16, 19, 25, 37, and 5 at the last administration of study treatment, every 24 weeks thereafter until disease progression or death, yearly thereafter up to 2 years after cessation of recruitment	OS was defined as the time from the date of enrollment to the date of death due to any cause. Participants were censored at the last date recorded in the CRF.
Overall Survival	BL, Day 1 of Weeks 1, 4, 7, 10, 13, 16, 19, 25, 37, and 52 at the last administration of study treatment, every 24 weeks thereafter until disease progression or death, yearly thereafter up to 2 years after cessation of recruitment	The time, in months, from BL to death due to any cause.