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

An Open-label Study of the Effect of First-line Herceptin Alone or in Combination With a Taxane on Tumor Response and Disease Progression in Patients With Metastatic Breast Cancer Who Relapsed After Receiving Adjuvant Herceptin for HER2-positive Early Breast Cancer

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.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: Trastuzumab; Drug: Taxane (docetaxel or paclitaxel)

• Study Type: Interventional
• Enrollment (Actual): 44
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Geelong, Victoria, Australia, 3220
• Austria
  • Klagenfurt, Austria, 9026
  • Salzburg, Austria, 5020
  • Vöcklabruck, Austria, 4840
  • Wien, Austria, 1090
• Belgium
  • Brussel, Belgium, 1090
  • Namur, Belgium, 5000
• Brazil
  • RS
    • Porto Alegre, RS, Brazil, 90610-000
    • Porto Alegre, RS, Brazil, 91350-200
• Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada, R2H 2A6
  • Ontario
    • Brampton, Ontario, Canada, L6R 3J7
    • Oshawa, Ontario, Canada, L1G 2B9
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2H1
• China
  • Beijing, China, 100021
  • Guangzhou, China, 510060
  • Shanghai, China, 200032
  • Wuhan, China, 430030
• Germany
  • Berlin, Germany, 12203
  • Düsseldorf, Germany, 40225
  • Hamburg, Germany, 20246
  • Krefeld, Germany, 47805
  • Köln, Germany, 50931
  • Lemgo, Germany, 32657
  • München, Germany, 81675
  • Tübingen, Germany, 72076
• Hungary
  • Budapest, Hungary, 1122
  • Budapest, Hungary, 1083
  • Budapest, Hungary, 1145
  • Budapest, Hungary, 1031
  • Kecskemet, Hungary, 6000
  • Szeged, Hungary, 6701
• Italy
  • Chieti, Italy, 66100
  • Genova, Italy, 16132
  • Roma, Italy, 00168
  • San Giovanni Rotondo, Italy, 71013
  • Sassari, Italy, 07100
• Mexico
  • Merida, Mexico, 97500
• Panama
  • Panama City, Panama, 83-0669
• Poland
  • Gdansk, Poland, 80-214
  • Gliwice, Poland, 44-101
  • Lodz, Poland, 94-306
• Russian Federation
  • Kazan, Russian Federation, 420029
  • Moscow, Russian Federation, 115478
  • Saint-Petersburg, Russian Federation, 197758
• Spain
  • Barcelona, Spain, 08036
  • Barcelona, Spain, 08035
  • Jaen, Spain, 23007
  • Madrid, Spain, 28041
  • Valencia, Spain, 46010
  • Valencia, Spain, 46009
  • Zaragoza, Spain, 50009
  • La Coruña
    • La Coruna, La Coruña, Spain, 15009
• Taiwan
  • Changhua, Taiwan, 500
  • Taipei, Taiwan
  • Taipei, Taiwan, 100
  • Taipei, Taiwan, 00112
  • Taoyuan, Taiwan, 333

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Trastuzumab Monotherapy; 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.	Drug: Trastuzumab; 4 mg/kg i.v. loading dose on Day 1, followed by 2 mg/kg i.v. weekly; or 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.; Other Names: Herceptin
Experimental: Trastuzumab, Taxane; 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.	Drug: Trastuzumab; 4 mg/kg i.v. loading dose on Day 1, followed by 2 mg/kg i.v. weekly; or 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.; Other Names: Herceptin; Drug: Taxane (docetaxel or paclitaxel); Docetaxel 100 mg/m2 i.v. every 3 weeks, or paclitaxel administered in a dose of 75 mg/m2 i.v. weekly or 175 mg/m2 i.v. every 3 weeks for at least 18 weeks, or more at the discretion of the investigator. Choice of taxane at the discretion of the investigator. Taxane may be administered at the same time, or 24 hours after, administration of trastuzumab.; Other Names: Docetaxel; Paclitaxel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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.	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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response - Percentage of Participants With Progressive Disease or Death	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.	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	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.	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
Progression-free Survival (PFS) - Percentage of Participants With Progressive Disease	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.	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
Progression-Free Survival	The time, in months, from BL to PFS event.	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
Percentage of Participants With Treatment Failure	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.	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
Time to Treatment Failure	The time, in months, from BL 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
Percentage of Participants With Clinical Benefit According to RECIST Guidelines	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.	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
Overall Survival - Percentage of Participants Who Died	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.	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
Overall Survival	The time, in months, from BL to death due to any cause.	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

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• Lang I, Bell R, Feng FY, Lopez RI, Jassem J, Semiglazov V, Al-Sakaff N, Heinzmann D, Chang J. Trastuzumab retreatment after relapse on adjuvant trastuzumab therapy for human epidermal growth factor receptor 2-positive breast cancer: final results of the Retreatment after HErceptin Adjuvant trial. Clin Oncol (R Coll Radiol). 2014 Feb;26(2):81-9. doi: 10.1016/j.clon.2013.08.011. Epub 2013 Sep 17.

Study record dates

Study Major Dates

• Study Start: October 1, 2005
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: May 17, 2007
• First Submitted That Met QC Criteria: May 17, 2007
• First Posted (Estimate): May 21, 2007

Study Record Updates

• Last Update Posted (Estimate): September 15, 2014
• Last Update Submitted That Met QC Criteria: September 9, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Docetaxel; Paclitaxel; Trastuzumab; Albumin-Bound Paclitaxel; Taxane
• Other Study ID Numbers: WO17299