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

• ClinicalTrials.gov Identifier: NCT00448279
• Recruitment Status: Completed
• First Posted: March 16, 2007
• Results First Posted: October 24, 2014
• Last Update Posted: October 24, 2014
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Breast Cancer	Drug: trastuzumab; Drug: Chemotherapy	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 58 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: April 2007
• Actual Primary Completion Date: September 2010
• Actual Study Completion Date: September 2010

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Chemotherapy Alone; Chemotherapy, schedule and dose at the investigator's discretion.	Drug: Chemotherapy; Schedule and dose at the investigator's discretion
Experimental: Chemotherapy, 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.	Drug: trastuzumab; 2mg/kg i.v. weekly, or 6mg/kg i.v. every 3 weeks; Other Name: Herceptin; Drug: Chemotherapy; Schedule and dose at the investigator's discretion

Outcome Measures

Primary Outcome Measures :

1. Progression-Free Survival (PFS) - Percentage of Participants With an Event [ Time Frame: 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.
2. Progression-Free Survival - Time to Event [ Time Frame: 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 :

1. Overall Survival (OS) - Percentage of Participants With an Event [ Time Frame: 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.
2. Overall Survival - Time to Event [ Time Frame: 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.
3. Percentage of Participants by Best Overall Response (BOR) [ Time Frame: 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.
4. Percentage of Participants With a Best Overall Response of CR or PR [ Time Frame: 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.

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

Italy

Avellino, Italy, 83100

Brescia, Italy, 25123

Candiolo, Italy, 10060

Carrara, Italy, 54033

Cona (Ferrara), Italy, 44124

Cosenza, Italy, 87100

Crotone - Kr, Italy, 88900

Fano, Italy, 61032

Firenze, Italy, 50139

Frattaminore, Italy, 80026

Genova, Italy, 16132

Lecce, Italy, 73100

Livorno, Italy, 57100

Mantova, Italy, 46100

Meldola, Italy, 47014

Napoli, Italy, 80131

Nocera Inferiore, Italy, 84014

Padova, Italy, 35128

Palermo, Italy, 90127

Pavia, Italy, 27100

Perugia, Italy, 06122

Pordenone, Italy, 33170

Potenza, Italy, 85100

Ragusa, Italy, 97100

Reggio Calabria, Italy, 89100

Rionero in Vulture, Italy, 85028

Roma, Italy, 00128

Roma, Italy, 00153

Salerno, Italy, 84131

San Giovanni Rotondo, Italy, 71013

Sassari, Italy, 07100

Sora, Italy, 03039

Taormina, Italy, 98030

Torino, Italy, 10125

Udine, Italy, 33100

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

More Information

• Responsible Party: Hoffmann-La Roche
• ClinicalTrials.gov Identifier: NCT00448279
• Other Study ID Numbers: ML18742
• First Posted: March 16, 2007
• Results First Posted: October 24, 2014
• Last Update Posted: October 24, 2014
• Last Verified: October 2014

Additional relevant MeSH terms:

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Trastuzumab; Antineoplastic Agents, Immunological; Antineoplastic Agents