THOR Study: A Study of Continued Herceptin (Trastuzumab) in Combination With Second Line Chemotherapy in Patients With HER2 Positive Metastatic Breast Cancer.

Phase 3

Completed

• Conditions: Breast Cancer
• Interventions: Drug: Chemotherapy; Drug: trastuzumab

• Registration Number: NCT00448279
• Lead Sponsor: Hoffmann-La Roche

Brief Summary

This 2 arm study will compare the efficacy and safety of continuation or discontinuation of Herceptin treatment in combination with 2nd line chemotherapy, in patients with HER2 positive metastatic breast cancer whose condition has progressed on 1st line chemotherapy plus Herceptin. Patients will be randomized either to continue or discontinue Herceptin treatment (2mg/kg iv infusion weekly, or 6mg/kg iv infusion every 3 weeks) while receiving 2nd line chemotherapy of the investigator's choice. The anticipated time on study treatment is until disease progression, and the target sample size is 100-500 individuals.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2007-03-15
• Study First Submitted QC: 2007-03-15
• Study First Posted: 2007-03-16
• Study Start: 2007-04
• Primary Completion: 2010-09
• Study Completion: 2010-09
• Status Verified: 2014-10
• Results First Submitted: 2014-10-21
• Results First Submitted QC: 2014-10-21
• Last Update Submitted: 2014-10-21
• Results First Posted: 2014-10-24
• Last Update Posted: 2014-10-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 58

Inclusion Criteria

• female patients, >=18 years of age;
• metastatic breast cancer;
• HER2 overexpression (IHC 3+ and/or FISH positive);
• disease progression during or after previous 1st line chemotherapy plus Herceptin;
• scheduled to receive 2nd line chemotherapy.

Exclusion Criteria

• incompatibility with previous Herceptin therapy;
• pregnancy.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Chemotherapy Alone	Chemotherapy	Chemotherapy, schedule and dose at the investigator's discretion.
Chemotherapy, Trastuzumab	trastuzumab	Trastuzumab, at the investigator's discretion, either 2 milligrams per kilogram (mg/kg) intravenous (i.v.) every 7 days or 6 mg/kg i.v. every 3 weeks. Chemotherapy, schedule and dose at the investigator's discretion.
Chemotherapy, Trastuzumab	Chemotherapy	Trastuzumab, at the investigator's discretion, either 2 milligrams per kilogram (mg/kg) intravenous (i.v.) every 7 days or 6 mg/kg i.v. every 3 weeks. Chemotherapy, schedule and dose at the investigator's discretion.

Primary Outcome Measures

Name	Time	Method
Progression-Free Survival (PFS) - Percentage of Participants With an Event	Baseline (BL) and every 8 weeks thereafter	PFS was defined as the time from randomization to the date of documented disease progression according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, or the date of occurrence of a second primary cancer, or date of death from any cause, whichever comes first. Participants were censored at the last tumour evaluation.
Progression-Free Survival - Time to Event	BL and every 8 weeks thereafter	The median time from randomization to PFS event. Participants were censored at the last tumour evaluation.

Secondary Outcome Measures

Name	Time	Method
Overall Survival - Time to Event	BL and every 8 weeks thereafter	The median time from randomization to OS event. Participants were censored at the last contact date at which the participant was known to be alive.
Percentage of Participants With a Best Overall Response of CR or PR	BL and every 8 weeks thereafter	BOR was defined as the best objective response observed during the treatment period according to RECIST version 1.1. CR: disappearance of all TLs, with any pathological lymph nodes (whether target or non-target) having a reduction in short axis to less than 10 mm. PR: at least a 30% decrease in the sum of diameters of TLs, taking as reference the BL sum diameters. PD: at least a 20% increase in the sum of diameters of TLs, taking as a reference the smallest sum on study (this included the BL sum if that is the smallest on study). In addition to the relative increase in 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. SD: neither sufficient shrinkages to qualify for PR, nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.
Overall Survival (OS) - Percentage of Participants With an Event	BL and every 8 weeks thereafter	OS was defined as the time from randomization to the date of death from any cause. Participants were censored at the last contact date at which the participant was known to be alive.
Percentage of Participants by Best Overall Response (BOR)	BL and every 8 weeks thereafter	BOR was defined as the best objective response observed during the treatment period according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Complete response (CR): disappearance of all target lesions (TLs), with any pathological lymph nodes (whether target or non-target) having a reduction in short axis to less than 10 millimeters (mm). Partial response (PR): at least a 30 percent (%) decrease in the sum of diameters of TLs, taking as reference the BL sum diameters. Progressive disease (PD): at least a 20% increase in the sum of diameters of TLs, taking as a reference the smallest sum on study (this included the BL sum if that is the smallest on study). In addition to the relative increase in 20%, the sum must also have demonstrated an absolute increase of at least 5 mm. Stable disease (SD) was defined as neither sufficient shrinkages to qualify for PR, nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.