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A Study of Herceptin (Trastuzumab) in Combination With 2nd-Line Chemotherapy in Patients With HER2 Positive Metastatic Breast Cancer.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT00444587
First received: March 7, 2007
Last updated: May 12, 2016
Last verified: May 2016
  Purpose
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 (6mg/kg iv infusion every 3 weeks) while receiving second-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 Intervention Phase
Breast Cancer
Drug: Second line chemotherapy
Drug: trastuzumab [Herceptin]
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multicenter Phase II Trial of Trastuzumab (Herceptin) Continuation in Combination With 2nd-line Chemotherapies After Progression on a 1st-line Chemotherapy Combined With Trastuzumab in Patients With HER2 Positive Metastatic Breast Cancer (Treatment Beyond Progression, TBP)

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Median Time to Disease Progression [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Time to disease progression (TTP) in days was defined as the time from enrollment to objective disease progression (all categories other than objective disease progression was set to be censored including death before progression). Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a nontarget lesion, or the appearance of new lesions. Tumor assessments were performed using computer tomography or magnetic resonance imaging. TTP as assessed by investigator, along with a recalculation done by computer algorithm is presented below. Median time was not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.


Secondary Outcome Measures:
  • Objective Response Rate [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Objective response rate (ORR) is defined as the percentage of participants with tumor shrinkage of a predefined amount. It is a combination of complete response (CR) and partial response (PR) and was assessed according to the RECIST criteria 1.0. Complete response refers to the disappearance of all target lesions and all non-target non-measurable lesions. Partial Response refers to an at least 30 percent decrease in the sum of longest diameter of target lesions, taking as reference the baseline sum longest diameter. Objective response rate was not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.

  • Clinical Benefit Rate [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Clinical benefit rate (CBR) was defined as the percentage of participants taking a benefit from the treatments. CBR includes 1) Complete response (CR): disappearance of all target lesions and all non-target non-measurable lesions 2) Partial response (PR) : >=30% decrease in the sum of the longest diameter of target lesions and 3) Stable disease (SD): non-PR and non-progressive disease. It was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST 1.0) and assessed by CT or MRI by the investigator. CBR was also assessed by computer. Clinical benefit rate was not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.

  • Median Time to Treatment Failure [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Time to treatment failure is defined as a composite endpoint measuring time (number of days) from enrollment to discontinuation of treatment or change in treatment for any reason, including disease progression, treatment toxicity and death. Median time to treatment failure was not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.

  • Overall Survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Overall Survival is defined as the time (number of days) between enrollment and the date of death due to any cause. Overall survival was not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.

  • Number of Participants With Any Adverse Events and Serious Adverse Events [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    An adverse event (AE) is any untoward medical occurrence in a participant who is administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect.

  • Biochemistry Safety Laboratory Parameters: Mean Serum Glutamic Oxaloacetic Transaminase, Serum Glutamic-pyruvic Transaminase and Alkali Phosphatase Levels [ Time Frame: Visit 1 [Screening Period (6 weeks prior to enrollment)] and Final study Assessments (Up to 5 years) ] [ Designated as safety issue: No ]
    Participants in the study were evaluated for the serum glutamic oxaloacetic transaminase (SGOT), serum glutamic-pyruvic transaminase (SGPT) and alkali phosphatase (ALP) at Visit 1 and final study assessments (Up to 5 years). Serum glutamic oxaloacetic transaminase, Serum glutamic-pyruvic transaminase and Alkali Phosphatase levels were not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.

  • Biochemistry Safety Laboratory Parameters: Mean Total Bilirubin and Serum Creatinine Levels [ Time Frame: Visit 1 [Screening Period (6 weeks prior to enrollment)] and Final study Assessments (Up to 5 years) ] [ Designated as safety issue: No ]
    Participants in the study were evaluated for the total bilirubin and serum creatinine. Total Bilirubin and serum creatinine levels were not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.

  • Biochemistry Safety Laboratory Parameters: Mean Albumin Levels [ Time Frame: Visit 1 [Screening Period (6 weeks prior to enrollment)] and Final study assessments (Up to 5 years) ] [ Designated as safety issue: No ]
    Participants in the study were evaluated for the albumin at Visit 1 and Final study assessments. Albumin levels were not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.

  • Biochemistry Safety Laboratory Parameters: Mean Urea, Sodium and Potassium Levels [ Time Frame: Visit 1 [Screening Period (6 weeks prior to enrollment)] and Final study assessments (Up to 5 years) ] [ Designated as safety issue: No ]
    Participants in the study were evaluated for the biochemical safety laboratory parameters urea, sodium and potassium. Urea, sodium and potassium levels were not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.

  • Hematology Safety Laboratory Parameters: Mean Hemoglobin Levels [ Time Frame: Visit 1 [Screening Period (6 weeks prior to enrollment)] and final study assessments (Up to 5 years) ] [ Designated as safety issue: No ]
    Participants in the study were evaluated for the Hemoglobin up to 5 years. Hemoglobin levels were not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.

  • Hematology Safety Laboratory Parameters: Mean Total Leukocytes Counts [ Time Frame: Visit 1 [Screening Period (6 weeks prior to enrollment)] and final study assessments (Up to 5 years) ] [ Designated as safety issue: No ]
    Participants in the study were evaluated for the total leukocytes up to 5 years. Total leukocytes counts were not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.

  • Hematology Safety Laboratory Parameters: Percent of Differential for Neutrophils, Basophils, Eosinophils, Lymphocytes and Monocytes Counts [ Time Frame: Visit 1 [Screening Period (6 weeks prior to enrollment)] and final study assessments (Up to 5 years) ] [ Designated as safety issue: No ]

    Participants in the study were evaluated for the Neutrophils, Basophils, Eosinophils, Lymphocytes and Monocytes at Visit 1 and final study assessments.

    Neutrophils, Basophils, Eosinophils, Lymphocytes and Monocytes counts were not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.


  • Hematology Safety Laboratory Parameter: Mean Platelets Counts [ Time Frame: Visit 1 [Screening Period (6 weeks prior to enrollment)] and final study assessments (Up to 5 years) ] [ Designated as safety issue: No ]
    Participants in the study were evaluated for the platelets at Visit 1 and final study assessments. Platelet counts were not assessed for 'Only Chemotherapy' group as randomization of participants was not feasible considering Trastuzumab widespread use in routine clinical practice.

  • Mean Left Ventricular Ejection Fraction [ Time Frame: Visit 0 [Screening period (6 weeks prior to enrollment)] and final study assessments (Up to 5 years). ] [ Designated as safety issue: No ]
    Left ventricular ejection fraction (LVEF) is a measure of the percent of blood ejected from the ventricle in one heartbeat. It is a measure of cardiac function and was assessed by echocardiogram or multigated angiogram at Visit 0 [Screening period (6 weeks prior to enrollment)] and final study assessments (Up to 5 years).


Enrollment: 114
Study Start Date: March 2007
Study Completion Date: August 2011
Primary Completion Date: August 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Trastuzumab + 2nd Line Chemotherapy Drug: Second line chemotherapy
As prescribed
Drug: trastuzumab [Herceptin]
6mg/kg iv every 3 weeks
Active Comparator: Only Chemotherapy Drug: Second line chemotherapy
As prescribed

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders 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 + Herceptin;
  • scheduled to receive 2nd line chemotherapy.

Exclusion Criteria:

  • concurrent immunotherapy or hormonal therapy;
  • anthracyclines as part of previous 1st line chemotherapy or planned 2nd line chemotherapy;
  • cardiac toxicity during previous 1st line chemotherapy + Herceptin;
  • history of other malignancy within last 5 years.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00444587

Locations
Bulgaria
Sofia, Bulgaria, 1527
Estonia
Tallinn, Estonia, 13419
Hungary
Budapest, Hungary, 1082
Budapest, Hungary, 1115
Budapest, Hungary, 1122
Budapest, Hungary, 1125
Budapest, Hungary, 1135
Budapest, Hungary, 1145
Debrecen, Hungary, 4032
Gyor, Hungary, 9023
Gyula, Hungary, 5700
Nyíregyháza, Hungary, 4400
Szeged, Hungary, 6725
Szekesfehervar, Hungary, 8000
Szombathely, Hungary, 9700
Israel
Haifa, Israel, 31096
Holon, Israel, 58100
Petach Tikva, Israel, 49100
Ramat Gan, Israel, 52621
Rehovot, Israel, 76100
Safed, Israel, 13110
Tel Aviv, Israel, 6423906
Zerifin, Israel, 70300
Lithuania
Kaunas, Lithuania, 50009
Vilnius, Lithuania, 08660
Macedonia, The Former Yugoslav Republic of
Skopje, Macedonia, The Former Yugoslav Republic of, 1000
Slovakia
Bratislava, Slovakia, 812 50
Kosice, Slovakia, 041 90
Turkey
Adana, Turkey, 01330
Ankara, Turkey, 06590
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT00444587     History of Changes
Other Study ID Numbers: ML19944 
Study First Received: March 7, 2007
Results First Received: March 16, 2016
Last Updated: May 12, 2016
Health Authority: Hungary: National Institute of Pharmacology

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Trastuzumab
Antineoplastic Agents

ClinicalTrials.gov processed this record on September 27, 2016