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

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

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00448279

Enrollment

Registered

2007-03-16

Start date

2007-04-30

Completion date

2010-09-30

Last updated

2014-10-24

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Breast Cancer

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.

Interventions

DRUGtrastuzumab

2mg/kg i.v. weekly, or 6mg/kg i.v. every 3 weeks

DRUGChemotherapy

Schedule and dose at the investigator's discretion

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

FEMALE

Age

18 Years to No maximum

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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.
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 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.
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.

Countries

Italy

Participant flow

Participants by arm

Arm	Count
Chemotherapy Alone Participants received chemotherapy until disease progression, unacceptable toxicity, or death; the schedule and dose at the investigator's discretion and per local prescribing guidelines and standard center practice. Allowed chemotherapy regimens included paclitaxel, gemcitabine, platinum compounds, docetaxel, capecitabine, or vinorelbine.	29
Chemotherapy + Trastuzumab Participants received trastuzumab at either 2 mg/kg, IV, every 7 days, or 6 mg/kg, IV, every 3 weeks, per the investigator's discretion. Participants also received chemotherapy; the schedule and dose at the investigator's discretion and per local prescribing guidelines and standard center practice. Allowed chemotherapy regimens included paclitaxel, gemcitabine, platinum compounds, docetaxel, capecitabine, or vinorelbine. Study treatment was administered until disease progression, unacceptable toxicity, or death.	29
Total	58

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	1	1
Overall Study	Disease progression	16	18
Overall Study	Lost to Follow-up	2	2
Overall Study	Other	6	4
Overall Study	Protocol Violation	0	1
Overall Study	Withdrawal by Subject	4	3

Baseline characteristics

Characteristic	Chemotherapy Alone	Chemotherapy + Trastuzumab	Total
Age, Continuous	59 years	57 years	58 years
Sex: Female, Male Female	29 Participants	29 Participants	58 Participants
Sex: Female, Male Male	0 Participants	0 Participants	0 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	26 / 26	26 / 28
serious Total, serious adverse events	4 / 26	1 / 28

Outcome results

Primary

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.

Time frame: Baseline (BL) and every 8 weeks thereafter

Population: ITT population

Arm	Measure	Value (NUMBER)
Chemotherapy Alone	Progression-Free Survival (PFS) - Percentage of Participants With an Event	58.6 percentage of participants
Chemotherapy + Trastuzumab	Progression-Free Survival (PFS) - Percentage of Participants With an Event	58.6 percentage of participants

Primary

Progression-Free Survival - Time to Event

The median time from randomization to PFS event. Participants were censored at the last tumour evaluation.