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A Study of Pertuzumab in Participants With Metastatic Breast Cancer

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ClinicalTrials.gov Identifier: NCT02491892
Recruitment Status : Completed
First Posted : July 8, 2015
Results First Posted : August 25, 2015
Last Update Posted : August 25, 2015
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE June 11, 2015
First Posted Date  ICMJE July 8, 2015
Results First Submitted Date  ICMJE July 22, 2015
Results First Posted Date  ICMJE August 25, 2015
Last Update Posted Date August 25, 2015
Study Start Date  ICMJE February 2003
Actual Primary Completion Date April 2005   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 24, 2015)
Percentage of Participants Achieving a Best Overall Response of Confirmed Complete Response (CR) or Partial Response (PR) [ Time Frame: Up to approximately 1 year (at Baseline; every 6 weeks for the first 8 cycles, then every 12 weeks until progression or death; and up to 4 weeks after initial response) ]
Objective tumor response was assessed using Response Evaluation Criteria in Solid Tumors (RECIST). Confirmed CR was defined as the disappearance of all target lesions, and confirmed PR was defined as at least at 30 percent (%) decrease in the sum of the longest diameters of target lesions. Response was to be confirmed at follow-up assessment completed within 4 weeks of the first documented response. The percentage of participants achieving a best overall response of CR or PR was calculated as [number of participants meeting the above criteria divided by the number analyzed] multiplied by 100.
Original Primary Outcome Measures  ICMJE
 (submitted: July 2, 2015)
Percentage of participants by best overall tumor response [ Time Frame: At 24 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 24, 2015)
  • Time to Response Among Participants Achieving a Best Overall Response of Confirmed CR or PR [ Time Frame: Up to approximately 1 year (at Baseline; every 6 weeks for the first 8 cycles, then every 12 weeks until progression or death; and up to 4 weeks after initial response) ]
    Objective tumor response was assessed using RECIST. Confirmed CR was defined as the disappearance of all target lesions, and confirmed PR was defined as at least at 30% decrease in the sum of the longest diameters of target lesions. Response was to be confirmed at follow-up assessment completed within 4 weeks of the first documented response. Time to response was defined as the time from treatment start to first documented response (ie, CR or PR). Participants with stable disease (SD) were censored from the last tumor assessment, and those with progressive disease (PD) or death were assigned an artificial censoring time of 1000 days. Time to response was estimated using Kaplan-Meier and expressed in weeks.
  • Duration of Response Among Participants Achieving a Best Overall Response of Confirmed CR or PR [ Time Frame: Up to approximately 1 year (at Baseline; every 6 weeks for the first 8 cycles, then every 12 weeks until progression or death; and up to 4 weeks after initial response) ]
    Objective tumor response was assessed using RECIST. Confirmed CR was defined as the disappearance of all target lesions, and confirmed PR was defined as at least at 30% decrease in the sum of the longest diameters of target lesions. Response was to be confirmed at follow-up assessment completed within 4 weeks of the first documented response. Duration of response was defined as the time from first documented response (ie, CR or PR) to PD or death. Participants who did not experience PD or death were censored from the last tumor assessment. Duration of response was estimated using Kaplan-Meier and expressed in weeks.
  • Percentage of Participants Achieving a Best Overall Response of Confirmed CR [ Time Frame: Up to approximately 1 year (at Baseline; every 6 weeks for the first 8 cycles, then every 12 weeks until progression or death; and up to 4 weeks after initial response) ]
    Objective tumor response was assessed using RECIST. Confirmed CR was defined as the disappearance of all target lesions. Response was to be confirmed at follow-up assessment completed within 4 weeks of the first documented response. The percentage of participants achieving a best overall response of CR was calculated as [number of participants meeting the above criteria divided by the number analyzed] multiplied by 100.
  • Duration of Response Among Participants Achieving a Best Overall Response of Confirmed CR [ Time Frame: Up to approximately 1 year (at Baseline; every 6 weeks for the first 8 cycles, then every 12 weeks until progression or death; and up to 4 weeks after initial response) ]
    Objective tumor response was assessed using RECIST. Confirmed CR was defined as the disappearance of all target lesions. Response was to be confirmed at follow-up assessment completed within 4 weeks of the first documented response. Duration of response was defined as the time from first documented response (ie, CR) to PD or death. Participants who did not experience PD or death were to be censored from the last tumor assessment. Duration of response was to be estimated using Kaplan-Meier.
  • Number of Participants Who Experienced PD or Death [ Time Frame: Up to approximately 1 year (at Baseline; every 6 weeks for the first 8 cycles, then every 12 weeks until progression or death; and up to 4 weeks after initial response) ]
    Objective tumor response was assessed using RECIST. PD was defined as the appearance of new lesion(s) or at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum obtained at Screening or during treatment. Participants who withdrew from the study early for insufficient therapeutic response without tumor assessment for PD were also included within the definition of PD.
  • Time to Progression [ Time Frame: Up to approximately 1 year (at Baseline; every 6 weeks for the first 8 cycles, then every 12 weeks until progression or death; and up to 4 weeks after initial response) ]
    Objective tumor response was assessed using RECIST. PD was defined as the appearance of new lesion(s) or at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum obtained at Screening or during treatment. Participants who withdrew from the study early for insufficient therapeutic response without tumor assessment for PD were also included within the definition of PD. Time to progression was defined as the time from treatment start to PD or death. Participants who did not experience PD or death were censored from the last tumor assessment. Time to progression was estimated using Kaplan-Meier and expressed in weeks.
  • Number of Participants Who Experienced PD or Withdrew From the Study Early [ Time Frame: Up to approximately 1 year (at Baseline; every 6 weeks for the first 8 cycles, then every 12 weeks until progression or death; and up to 4 weeks after initial response) ]
    Objective tumor response was assessed using RECIST. PD was defined as the appearance of new lesion(s) or at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum obtained at Screening or during treatment.
  • Time to Treatment Failure [ Time Frame: Up to approximately 1 year (at Baseline; every 6 weeks for the first 8 cycles, then every 12 weeks until progression or death; and up to 4 weeks after initial response) ]
    Objective tumor response was assessed using RECIST. PD was defined as the appearance of new lesion(s) or at least a 20% increase in the sum of the longest diameters of target lesions, taking as reference the smallest sum obtained at Screening or during treatment. Time to treatment failure was defined as the time from treatment start to PD or early withdrawal from the study for death, toxicity, refusal/noncompliance, insufficient therapeutic response, or failure to return. Participants who did not experience PD or who did not withdraw from the study early were censored from the last tumor assessment. Time to treatment failure was estimated using Kaplan-Meier and expressed in weeks.
  • Percentage of Participants Who Died [ Time Frame: Up to approximately 2 years (from start of treatment until death) ]
    The percentage of participants who died was calculated as [number of participants with event divided by the number analyzed] multiplied by 100.
  • Overall Survival [ Time Frame: Up to approximately 2 years (from start of treatment until death) ]
    Overall survival was defined as the time from treatment start to death. Participants who did not die during follow-up were to be censored from the last known alive date. Overall survival was to be estimated using Kaplan-Meier.
  • Percentage of Participants Achieving a Best Overall Response of SD [ Time Frame: Up to approximately 1 year (at Baseline; every 6 weeks for the first 8 cycles, then every 12 weeks until progression or death; and up to 4 weeks after initial response) ]
    Objective tumor response was assessed using RECIST. SD was defined as neither sufficient shrinkage to quality for PR nor sufficient increase to qualify for PD. The percentage of participants achieving a best overall response of SD was calculated as [number of participants meeting the above criteria divided by the number analyzed] multiplied by 100.
  • Apparent Half-Life (t1/2) of Pertuzumab [ Time Frame: Pre-dose and within 15 minutes of the end of infusion on Day 1 of each cycle, and on Days 8 and 15 of Cycles 1 and 2 ]
    Serum samples were obtained for pharmacokinetic (PK) assessment using a receptor-binding, enzyme-linked immunosorbent assay (ELISA). Pertuzumab concentrations at each collection point were used to determine the apparent t1/2 by non-compartmental analysis, defined as the time elapsed for pertuzumab concentrations to decrease by 50%. The derived value was averaged among all participants and expressed in days.
  • Maximum Plasma Concentration (Cmax) of Pertuzumab [ Time Frame: Pre-dose and within 15 minutes of the end of infusion on Day 1 of each cycle, and on Days 8 and 15 of Cycles 1 and 2 ]
    Serum samples were obtained for PK assessment using a receptor-binding ELISA. The maximum observed pertuzumab concentration across all collection points was documented. Cmax was averaged among all participants and expressed in micrograms per milliliter (mcg/mL).
  • Time to Maximum Plasma Concentration (Tmax) of Pertuzumab [ Time Frame: Pre-dose and within 15 minutes of the end of infusion on Day 1 of each cycle, and on Days 8 and 15 of Cycles 1 and 2 ]
    Serum samples were obtained for PK assessment using a receptor-binding ELISA. The time of maximum observed pertuzumab concentration across all collection points was documented. Tmax was averaged among all participants and expressed in days.
  • Area Under the Concentration-Time Curve (AUC) of Pertuzumab [ Time Frame: Pre-dose and within 15 minutes of the end of infusion on Day 1 of each cycle, and on Days 8 and 15 of Cycles 1 and 2 ]
    Serum samples were obtained for PK assessment using a receptor-binding ELISA. Pertuzumab concentrations at each collection point were used to determine AUC to the last measurable observation (AUClast) and AUC extrapolated to infinity (AUCinf) by non-compartmental analysis. The derived values were averaged among all participants and expressed in days by micrograms per milliliter (days*mcg/mL).
  • Systemic Clearance (CL) of Pertuzumab [ Time Frame: Pre-dose and within 15 minutes of the end of infusion on Day 1 of each cycle, and on Days 8 and 15 of Cycles 1 and 2 ]
    Serum samples were obtained for PK assessment using a receptor-binding ELISA. Pertuzumab concentrations at each collection point were used to determine CL by non-compartmental analysis, defined as the rate at which pertuzumab was removed from the body. The derived value was averaged among all participants and expressed in milliliters per day (mL/day).
  • Volume of Distribution at Steady State (Vss) of Pertuzumab [ Time Frame: Pre-dose and within 15 minutes of the end of infusion on Day 1 of each cycle, and on Days 8 and 15 of Cycles 1 and 2 ]
    Serum samples were obtained for PK assessment using a receptor-binding ELISA. Pertuzumab concentrations at each collection point were used to determine the Vss by non-compartmental analysis, defined as the theoretical volume at which the total amount of pertuzumab would be uniformly distributed to produce the desired concentration. The derived value was averaged among all participants and expressed in milliliters (mL).
  • Mean Residence Time (MRT) of Pertuzumab [ Time Frame: Pre-dose and within 15 minutes of the end of infusion on Day 1 of each cycle, and on Days 8 and 15 of Cycles 1 and 2 ]
    Serum samples were obtained for PK assessment using a receptor-binding ELISA. Pertuzumab concentrations at each collection point were used to determine the MRT by non-compartmental analysis. The derived value was averaged among all participants and expressed in days.
  • Number of Participants Experiencing a Drop in Left Ventricular Ejection Fraction (LVEF) to a Value of Less Than 50% [ Time Frame: Up to approximately 1 year (at Baseline; at the end of Cycles 2, 4, 8, 12, and 16; and up to 7 weeks following the last infusion) ]
    Echocardiography was performed to determine LVEF, defined as the volume of blood pumped from the left ventricle as a percentage of end-diastolic volume. Theoretically, LVEF may range from 0 to 100%. The number of participants experiencing a drop in LVEF greater than or equal to (≥) 10 or 15 percentage points to a final LVEF of less than (<) 50% is reported here.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 2, 2015)
  • Time to response [ Time Frame: At Screening and every 2 cycles (6 weeks) thereafter (up to approximately 1 year) ]
  • Survival [ Time Frame: Every 12 weeks until disease progression, death, or 12 months from last participant enrolled (up to approximately 1 year) ]
  • Incidence of adverse events [ Time Frame: From Day 1 until the final study visit (up to approximately 1 year) ]
  • Left ventricular ejection fraction (LVEF) [ Time Frame: At Screening and Cycles 2, 4, 8, 12, and 16 (cycle length of 21 days) and at the final study visit (up to approximately 1 year) ]
  • Maximum serum concentration (Cmax) of rhuMAb 2C4 [ Time Frame: Pre-dose and post-dose on Day 1 of each cycle, and also on Days 8 and 15 of Cycles 1 and 2 (cycle length of 21 days) ]
  • Percentage of participants with objective stable disease [ Time Frame: At Screening and every 2 cycles (6 weeks) thereafter (up to approximately 1 year) ]
  • Duration of overall tumor response [ Time Frame: At Screening and every 2 cycles (6 weeks) thereafter (up to approximately 1 year) ]
  • Duration of complete response [ Time Frame: At Screening and every 2 cycles (6 weeks) thereafter (up to approximately 1 year) ]
  • Time to progression [ Time Frame: At Screening and every 2 cycles (6 weeks) thereafter (up to approximately 1 year) ]
  • Time to treatment failure [ Time Frame: At Screening and every 2 cycles (6 weeks) thereafter (up to approximately 1 year) ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Pertuzumab in Participants With Metastatic Breast Cancer
Official Title  ICMJE Open-Label, Phase II, Multicenter, Randomized Study of Efficacy and Safety for Two Different Doses of a Recombinant Humanized Antibody to HER2 (rhuMAb 2C4) Administered Every 3 Weeks to Patients With Metastatic Breast Cancer With Low Expression of HER2
Brief Summary This study will evaluate the efficacy and safety of pertuzumab (rhuMAb 2C4) in participants with metastatic breast cancer which has progressed during or after standard chemotherapy and which is not amenable to curative therapy. Those who are maintaining a response to therapy or who have stable disease at the end of the formal study period will continue treatment until disease progression or unacceptable toxicity. Approximately 120 participants will be enrolled.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Breast Cancer
Intervention  ICMJE Drug: Pertuzumab
Participants will receive one of two IV treatment regimens with pertuzumab: either 420 mg every 3 weeks, with an initial 840-mg loading dose, or 1050 mg every 3 weeks with no loading dose administered.
Other Name: rhuMAb 2C4
Study Arms  ICMJE
  • Experimental: Pertuzumab 1050 mg
    Participants will not receive a loading dose, but will receive pertuzumab 1050 milligrams (mg) via intravenous (IV) infusion every 3 weeks until unacceptable toxicity or disease progression.
    Intervention: Drug: Pertuzumab
  • Experimental: Pertuzumab 420 mg
    Participants will receive a loading dose of 840 mg via IV infusion at the first infusion of pertuzumab, followed by a maintenance dose of 420 mg every 3 weeks until unacceptable toxicity or disease progression.
    Intervention: Drug: Pertuzumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 2, 2015)
79
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE April 2005
Actual Primary Completion Date April 2005   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Females at least 18 years of age
  • Histologically-confirmed metastatic breast cancer with low HER2 expression and at least one measurable lesion according to Response Evaluation Criteria in Solid Tumors (RECIST)
  • Karnofsky performance status at least 80%
  • Disease progression on/after up to 2 different chemotherapy regimens, including an anthracycline-containing therapy
  • Left ventricular ejection fraction (LVEF) at least 50%
  • Adequate liver function

Exclusion Criteria:

  • Pleural effusions, ascites, or bone lesions as the only manifestation(s) of cancer
  • Pulmonary or central nervous system (CNS) metastases
  • Chemotherapy, radiotherapy, or immunotherapy within 4 weeks; or hormone therapy within 2 weeks of Day 1
  • Previous treatment with any drug that targets the HER2 receptor family
  • Previous treatment with corticosteroids as cancer therapy
  • History of significant cardiac disease
  • Major surgery or trauma within 4 weeks of Day 1
  • Pregnant or lactating women
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Belgium,   Finland,   Germany,   Italy,   Netherlands,   Spain,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02491892
Other Study ID Numbers  ICMJE BO16934
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Hoffmann-La Roche
Study Sponsor  ICMJE Hoffmann-La Roche
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date August 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP