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

Study Overview
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Brief Summary
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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.

Official Title
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A Randomized, Open-label Study to Compare Progression-free Survival in Patients With HER2 Positive Metastatic Breast Cancer Who Continue or Discontinue Herceptin in Combination With 2nd Line Chemotherapy, Having Progressed on 1st Line Chemotherapy in Combination With Herceptin

Conditions
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Breast Cancer

Intervention / Treatment
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* Drug: trastuzumab
* Drug: Chemotherapy


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Chemotherapy Alone<br>Chemotherapy, schedule and dose at the investigator's discretion. | Drug: Chemotherapy<br>* Schedule and dose at the investigator's discretion<br>|
| Experimental: Chemotherapy, Trastuzumab<br>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. | Drug: trastuzumab<br>* 2mg/kg i.v. weekly, or 6mg/kg i.v. every 3 weeks<br>* Other names: Herceptin;Drug: Chemotherapy<br>* Schedule and dose at the investigator's discretion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) - Percentage of Participants With an Event | 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. | Baseline (BL) and every 8 weeks thereafter | 
| Progression-Free Survival - Time to Event | The median time from randomization to PFS event. Participants were censored at the last tumour evaluation. | BL and every 8 weeks thereafter | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) - Percentage of Participants With an Event | 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. | BL and every 8 weeks thereafter | 
| Overall Survival - Time to Event | 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. | BL and every 8 weeks thereafter | 
| Percentage of Participants by Best Overall Response (BOR) | 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. | BL and every 8 weeks thereafter | 
| Percentage of Participants With a Best Overall Response of CR or PR | 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. | BL and every 8 weeks thereafter |