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Benefit of Adding Trastuzumab to Second Line Chemotherapy in Breast Cancer Patients Previously Treated With Trastuzumab

Primary Purpose

Breast Cancer

Status
Terminated
Phase
Phase 2
Locations
Spain
Study Type
Interventional
Intervention
Vinorelbine
Capecitabine
Trastuzumab
Sponsored by
Spanish Breast Cancer Research Group
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Breast Cancer focused on measuring HER2 positive breast cancer., Progression to trastuzumab and taxanes.

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria: Written informed consent. Women older than 18 years old. HER2 positive breast cancer with histological diagnoses. Non-operable locally advanced or metastatic disease, previously treated with trastuzumab and taxanes. Measurable or non-measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST). Disease progression during or after treatment with trastuzumab and taxanes. Maximum of 1 previous chemotherapy line for advanced or metastatic disease. Previous radiotherapy is allowed if radiated area is not the only documented lesion. At least 4 weeks since the last administration of antineoplastic treatment and all toxicities resolved. Performance status Eastern Cooperative Oncology Group (ECOG) >=2. Life expectancy of at least 12 weeks. Left Ventricular Ejection Fraction (LVEF) evaluation (>=50%) in previous 4 weeks. Hematology: neutrophils >=1.5 x 10e9/l; platelets >= 100 x 10e9/l; hemoglobin >= 10 mg/dl Hepatic function: total bilirubin <= 1.5 x under normal limit (UNL); Aspartate aminotransferase (SGOT) and Alanine aminotransferase (SGPT) and alkaline phosphatase <= 2.5 x UNL, or <=5 x UNL if hepatic lesions present Renal function: creatinine <= 175 µmol/l (2 mg/dl); creatinine clearance >= 60 ml/min. Patients able to comply with treatment and follow-up. Negative pregnancy test in the previous 14 days. Adequate contraceptive method during treatment and up to 3 months after finalised. Brain metastatic lesions are allowed provided all other criteria are met. Male who met inclusion criteria are eligible. Exclusion Criteria: History of hypersensitivity to vinorelbine, trastuzumab, rat proteins or trastuzumab components. History of dyspnea at rest, or chronic oxygen therapy required. Active infection. Second malignancy, except for cervical in situ carcinoma, basal skin carcinoma, adequately treated. Previous malignancies with a 5 year disease free survival are allowed. Pregnant or lactating women. Any other serious medical pathology, such as congestive heart failure, unstable angina, history of myocardial infarction during the previous year, uncontrolled hypertension or high risk arrhythmias. History of neurological or psychiatric disorders, which could preclude the patients to free informed consent. Active uncontrolled infection. Active peptic ulcer, unstable diabetes mellitus. Concomitant treatment with other investigational products. Participation in other clinical trials with a non-marketed drug in the 30 previous days before randomization. Concomitant treatment with other therapy for cancer.

Sites / Locations

  • Spanish Breast Cancer Research Group (GEICAM)

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Arm A: VX

Arm B: VXH

Arm Description

Vinorelbine and capecitabine (VX): vinorelbine 25 mg/m2 iv, days 1 and 8 each cycle (21 days), followed of capecitabine 825 mg/m2, orally, twice a day, days 1-14 each cycle (21 days).

Vinorelbine, capecitabine and trastuzumab (VXH): vinorelbine 25 mg/m2 iv, days 1 and 8 each cycle (21 days), followed of capecitabine 825 mg/m2, orally, twice a day, days 1-14 each cycle (21 days) and trastuzumab 4 mg/kg iv (loading dose first week), followed by 2 mg/kg weekly.

Outcomes

Primary Outcome Measures

Clinical benefit rate
Clinical benefit rate is defined as the rate of objective responses (complete responses and partial responses to treatment) and stabilizations, with a minimum duration of 24 weeks.

Secondary Outcome Measures

Time to progression (TTP)
Tumor assessments will be performed until disease progression in order to evaluate the TTP. TTP is defined as the time from the date of the first dose to the first date of objectively determined progressive disease. For patients not known to have objectively-determined progressive disease, TTP will be censored at the date of the last objective progression-free assessment. For patients who receive subsequent systemic anticancer therapy (after discontinuation from the study treatment) prior to objective disease progression, TTP will be censored at the date of last objective progression-free assessment prior to the initiation of postdiscontinuation systemic anticancer therapy.
Objective Response Rate (ORR)
Tumor response will be assessed using RECIST criteria. The best response across all treatment will be recorded. ORR is defined as the percentage of patients with a complete or partial response out of the patients who had measurable disease at baseline.
Response Duration (RD)
RD is defined as the time from the date when the measurement criteria are met for complete response (CR) or partial response (PR) (whichever status is recorded first) until the date of first observation of disease progression or death occurred. For responding patients not known to have died as of the data cut-off date and who do not have progression, duration of response will be censored at the date of last visit with adequate assessment. For responding patients who receive subsequent anticancer therapy (after discontinuation from the study treatment) prior to progression, duration of response will be censored at the date of last visit with adequate assessment prior to the initiation of post-discontinuation anticancer therapy.
The Number of Participants Who Experienced Adverse Events (AE)
All AE suffered by patients will be recorded and graduated by the NCI CTCAE v1.0.
Overall Survival (OS)
OS was defined as the time elapsed from first treatment until death from any cause.

Full Information

First Posted
August 12, 2005
Last Updated
February 25, 2019
Sponsor
Spanish Breast Cancer Research Group
Collaborators
Hoffmann-La Roche
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1. Study Identification

Unique Protocol Identification Number
NCT00130507
Brief Title
Benefit of Adding Trastuzumab to Second Line Chemotherapy in Breast Cancer Patients Previously Treated With Trastuzumab
Official Title
Randomized Trial to Assess the Benefit of Adding Trastuzumab to Capecitabine and Vinorelbine as Second Line for HER2positive Breast Cancer Patients With Locally Advanced or Metastatic Disease, Previously Treated With Trastuzumab and Taxanes
Study Type
Interventional

2. Study Status

Record Verification Date
February 2019
Overall Recruitment Status
Terminated
Why Stopped
A new alternative treatment caused the decrease in the rhythm of recruitment.
Study Start Date
November 4, 2005 (Actual)
Primary Completion Date
June 2009 (Actual)
Study Completion Date
July 25, 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Spanish Breast Cancer Research Group
Collaborators
Hoffmann-La Roche

4. Oversight

5. Study Description

Brief Summary
Eligible patients must receive vinorelbine plus capecitabine, with or without trastuzumab, until disease progression or unbearable toxicity. Cycles will be administered every 3 weeks.Human epidermal growth factor receptor 2 (HER2) status must be locally assessed by immunohistochemistry (IHC). All 3+ patients are eligible. In 2+ patients, HER2 status must be confirmed by fluorescence in situ hybridization (FISH).
Detailed Description
Principal outcome is clinical benefit (complete + partial responses + stable disease). Sample size in each arm has been estimated with the Fleming method. Previous data show a clinical benefit rate of vinorelbine plus capecitabine around 50%. The researchers assume trastuzumab can increase it by 20%. With an alpha error of 0.05 and 80% power, 37 patients per arm are needed. This is a randomised phase II trial. With a minimum expected benefit rate of 50%, at least 36 patients are needed to choose, with a 90% of probability to be right, the best treatment arm, providing it increases benefit rate at least by 15%. Assuming a drop-out rate of 10%, the total number of patients needed is 82, 41 per treatment arm. Patients will be stratified as per investigational site, and presence of visceral metastatic lesion (liver, lung, pleura, heart, peritoneum, suprarenal glands). All patients must receive 2 cycles. If no disease progression is detected, treatment must continue until progression or unbearable toxicity.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Breast Cancer
Keywords
HER2 positive breast cancer., Progression to trastuzumab and taxanes.

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
14 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm A: VX
Arm Type
Active Comparator
Arm Description
Vinorelbine and capecitabine (VX): vinorelbine 25 mg/m2 iv, days 1 and 8 each cycle (21 days), followed of capecitabine 825 mg/m2, orally, twice a day, days 1-14 each cycle (21 days).
Arm Title
Arm B: VXH
Arm Type
Experimental
Arm Description
Vinorelbine, capecitabine and trastuzumab (VXH): vinorelbine 25 mg/m2 iv, days 1 and 8 each cycle (21 days), followed of capecitabine 825 mg/m2, orally, twice a day, days 1-14 each cycle (21 days) and trastuzumab 4 mg/kg iv (loading dose first week), followed by 2 mg/kg weekly.
Intervention Type
Drug
Intervention Name(s)
Vinorelbine
Other Intervention Name(s)
Navelbine
Intervention Type
Drug
Intervention Name(s)
Capecitabine
Other Intervention Name(s)
Xeloda
Intervention Type
Drug
Intervention Name(s)
Trastuzumab
Other Intervention Name(s)
Herceptin
Primary Outcome Measure Information:
Title
Clinical benefit rate
Description
Clinical benefit rate is defined as the rate of objective responses (complete responses and partial responses to treatment) and stabilizations, with a minimum duration of 24 weeks.
Time Frame
Through study completion, an average of 1 year
Secondary Outcome Measure Information:
Title
Time to progression (TTP)
Description
Tumor assessments will be performed until disease progression in order to evaluate the TTP. TTP is defined as the time from the date of the first dose to the first date of objectively determined progressive disease. For patients not known to have objectively-determined progressive disease, TTP will be censored at the date of the last objective progression-free assessment. For patients who receive subsequent systemic anticancer therapy (after discontinuation from the study treatment) prior to objective disease progression, TTP will be censored at the date of last objective progression-free assessment prior to the initiation of postdiscontinuation systemic anticancer therapy.
Time Frame
Through study completion, an average of 1 year
Title
Objective Response Rate (ORR)
Description
Tumor response will be assessed using RECIST criteria. The best response across all treatment will be recorded. ORR is defined as the percentage of patients with a complete or partial response out of the patients who had measurable disease at baseline.
Time Frame
Through study completion, an average of 1 year
Title
Response Duration (RD)
Description
RD is defined as the time from the date when the measurement criteria are met for complete response (CR) or partial response (PR) (whichever status is recorded first) until the date of first observation of disease progression or death occurred. For responding patients not known to have died as of the data cut-off date and who do not have progression, duration of response will be censored at the date of last visit with adequate assessment. For responding patients who receive subsequent anticancer therapy (after discontinuation from the study treatment) prior to progression, duration of response will be censored at the date of last visit with adequate assessment prior to the initiation of post-discontinuation anticancer therapy.
Time Frame
Through study completion, an average of 1 year
Title
The Number of Participants Who Experienced Adverse Events (AE)
Description
All AE suffered by patients will be recorded and graduated by the NCI CTCAE v1.0.
Time Frame
Through study completion, an average of 1 year
Title
Overall Survival (OS)
Description
OS was defined as the time elapsed from first treatment until death from any cause.
Time Frame
Through study completion, an average of 1 year

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Written informed consent. Women older than 18 years old. HER2 positive breast cancer with histological diagnoses. Non-operable locally advanced or metastatic disease, previously treated with trastuzumab and taxanes. Measurable or non-measurable disease as per Response Evaluation Criteria in Solid Tumors (RECIST). Disease progression during or after treatment with trastuzumab and taxanes. Maximum of 1 previous chemotherapy line for advanced or metastatic disease. Previous radiotherapy is allowed if radiated area is not the only documented lesion. At least 4 weeks since the last administration of antineoplastic treatment and all toxicities resolved. Performance status Eastern Cooperative Oncology Group (ECOG) >=2. Life expectancy of at least 12 weeks. Left Ventricular Ejection Fraction (LVEF) evaluation (>=50%) in previous 4 weeks. Hematology: neutrophils >=1.5 x 10e9/l; platelets >= 100 x 10e9/l; hemoglobin >= 10 mg/dl Hepatic function: total bilirubin <= 1.5 x under normal limit (UNL); Aspartate aminotransferase (SGOT) and Alanine aminotransferase (SGPT) and alkaline phosphatase <= 2.5 x UNL, or <=5 x UNL if hepatic lesions present Renal function: creatinine <= 175 µmol/l (2 mg/dl); creatinine clearance >= 60 ml/min. Patients able to comply with treatment and follow-up. Negative pregnancy test in the previous 14 days. Adequate contraceptive method during treatment and up to 3 months after finalised. Brain metastatic lesions are allowed provided all other criteria are met. Male who met inclusion criteria are eligible. Exclusion Criteria: History of hypersensitivity to vinorelbine, trastuzumab, rat proteins or trastuzumab components. History of dyspnea at rest, or chronic oxygen therapy required. Active infection. Second malignancy, except for cervical in situ carcinoma, basal skin carcinoma, adequately treated. Previous malignancies with a 5 year disease free survival are allowed. Pregnant or lactating women. Any other serious medical pathology, such as congestive heart failure, unstable angina, history of myocardial infarction during the previous year, uncontrolled hypertension or high risk arrhythmias. History of neurological or psychiatric disorders, which could preclude the patients to free informed consent. Active uncontrolled infection. Active peptic ulcer, unstable diabetes mellitus. Concomitant treatment with other investigational products. Participation in other clinical trials with a non-marketed drug in the 30 previous days before randomization. Concomitant treatment with other therapy for cancer.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Hospital Clinic i Provincial
Official's Role
Study Director
Facility Information:
Facility Name
Spanish Breast Cancer Research Group (GEICAM)
City
San Sebastián de los Reyes
State/Province
Madrid
ZIP/Postal Code
28700
Country
Spain

12. IPD Sharing Statement

Links:
URL
http://www.geicam.org
Description
Click here for more information about this study.

Learn more about this trial

Benefit of Adding Trastuzumab to Second Line Chemotherapy in Breast Cancer Patients Previously Treated With Trastuzumab

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