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A Study Evaluating Pertuzumab (Perjeta) Combined With Trastuzumab (Herceptin) and Standard Anthracycline-based Chemotherapy in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Locally Advanced, Inflammatory, or Early-stage Breast Cancer

NCT02132949

Description:

This multicenter, non-randomized, open-label, phase 2 study is designed to evaluate the safety and efficacy of pertuzumab (Perjeta) in combination with trastuzumab (Herceptin) and anthracycline-based chemotherapy as neoadjuvant treatment in participants with HER2-positive locally advanced, inflammatory, or early-stage breast cancer. Each investigator will choose a treatment regimen (A or B) for all of their participants to follow. Treatment regimen A (for Cohort A) will include dose-dense doxorubicin and cyclophosphamide (ddAC), followed by paclitaxel, with pertuzumab and trastuzumab given from the start of paclitaxel. Treatment regimen B (for Cohort B) will include 5-fluorouracil, epirubicin, and cyclophosphamide (FEC), followed by docetaxel, with pertuzumab and trastuzumab given from the start of docetaxel. Participants in both cohorts will subsequently undergo surgical treatment and then resume pertuzumab and trastuzumab treatment.

Related Conditions:
  • Breast Carcinoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study Evaluating Pertuzumab (Perjeta) Combined With Trastuzumab (Herceptin) and Standard Anthracycline-based Chemotherapy in Participants With Human Epidermal Growth Factor Receptor 2 (HER2)-Positive Locally Advanced, Inflammatory, or Early-stage Breast Cancer
  • Official Title: A Multicenter, Multinational, Phase II Study to Evaluate Perjeta in Combination With Herceptin and Standard Neoadjuvant Anthracycline-Based Chemotherapy in Patients With HER2-Positive, Locally Advanced, Inflammatory, or Early-Stage Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: WO29217
  • NCT ID: NCT02132949

Conditions

  • Breast Cancer

Interventions

DrugSynonymsArms
5-FluorouracilCohort B: FEC, Docetaxel, Pertuzumab, Trastuzumab
CyclophosphamideCohort A: ddAC, Paclitaxel, Pertuzumab, Trastuzumab
DocetaxelCohort B: FEC, Docetaxel, Pertuzumab, Trastuzumab
DoxorubicinCohort A: ddAC, Paclitaxel, Pertuzumab, Trastuzumab
EpirubicinCohort B: FEC, Docetaxel, Pertuzumab, Trastuzumab
paclitaxelCohort A: ddAC, Paclitaxel, Pertuzumab, Trastuzumab
PertuzumabPerjetaCohort A: ddAC, Paclitaxel, Pertuzumab, Trastuzumab
TrastuzumabHerceptinCohort A: ddAC, Paclitaxel, Pertuzumab, Trastuzumab

Purpose

This multicenter, non-randomized, open-label, phase 2 study is designed to evaluate the safety and efficacy of pertuzumab (Perjeta) in combination with trastuzumab (Herceptin) and anthracycline-based chemotherapy as neoadjuvant treatment in participants with HER2-positive locally advanced, inflammatory, or early-stage breast cancer. Each investigator will choose a treatment regimen (A or B) for all of their participants to follow. Treatment regimen A (for Cohort A) will include dose-dense doxorubicin and cyclophosphamide (ddAC), followed by paclitaxel, with pertuzumab and trastuzumab given from the start of paclitaxel. Treatment regimen B (for Cohort B) will include 5-fluorouracil, epirubicin, and cyclophosphamide (FEC), followed by docetaxel, with pertuzumab and trastuzumab given from the start of docetaxel. Participants in both cohorts will subsequently undergo surgical treatment and then resume pertuzumab and trastuzumab treatment.

Trial Arms

NameTypeDescriptionInterventions
Cohort A: ddAC, Paclitaxel, Pertuzumab, TrastuzumabExperimentalddAC: dose dense doxorubicin and cyclophosphamide. Participants will receive doxorubicin and cyclophosphamide every 2 weeks (q2w) for 4 cycles, followed by paclitaxel for 12 weeks, with pertuzumab and trastuzumab given every 3 weeks (q3w) (8 cycles of chemotherapy in total prior to surgery) from the start of paclitaxel. Following surgery, participants will receive further adjuvant pertuzumab and trastuzumab q3w (13 cycles), such that a total of 17 cycles of pertuzumab and trastuzumab therapy are given during the study.
  • Cyclophosphamide
  • Doxorubicin
  • paclitaxel
  • Pertuzumab
  • Trastuzumab
Cohort B: FEC, Docetaxel, Pertuzumab, TrastuzumabExperimentalFEC: 5-fluorouracil, epirubicin and cyclophosphamide. Participants will receive 5-fluorouracil, epirubicin, and cyclophosphamide given q3w for 4 cycles, followed by docetaxel q3w for 4 cycles, with pertuzumab and trastuzumab given q3w (8 cycles of chemotherapy in total prior to surgery) from the start of docetaxel. Following surgery, participants will receive further adjuvant pertuzumab and trastuzumab q3w (13 cycles), such that a total of 17 cycles of pertuzumab and trastuzumab therapy are given during the study.
  • 5-Fluorouracil
  • Cyclophosphamide
  • Docetaxel
  • Epirubicin
  • Pertuzumab
  • Trastuzumab

Eligibility Criteria

        Inclusion Criteria:

          -  Male and female participants with locally advanced, inflammatory, or early-stage,
             unilateral, and histologically confirmed invasive breast cancer. Participants with
             inflammatory breast cancer must be able to have a core needle biopsy

          -  Primary tumor greater than (>) 2 centimeters (cm) in diameter, or > 5 millimeters (mm)
             in diameter and node-positive

          -  HER2-positive breast cancer confirmed by a central laboratory

          -  Availability of tumor tissue specimen

          -  Baseline LVEF greater than or equal to (>/=) 55%

          -  Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to
             (</=) 1

          -  At least 4 weeks since major unrelated surgery, with full recovery

          -  Women of childbearing potential and male participants with partners of childbearing
             potential must agree to use a "highly effective" non-hormonal form of contraception or
             two "effective" forms of non-hormonal contraception by the patient and/or partner.
             Contraception must continue for the duration of study treatment and for at least 7
             months after the last dose of study treatment

        Exclusion Criteria:

          -  Metastatic disease (Stage IV) or bilateral breast cancer

          -  Participants who have had an incisional biopsy of the primary tumor or the primary
             tumor excised

          -  Prior breast or non-breast malignancy within 5 years prior to study entry, except for
             carcinoma in situ and basal cell and squamous cell carcinoma of the skin. Participants
             with malignancies occurring more than 5 years prior to study entry are permitted if
             curatively treated

          -  Any previous systemic therapy (including chemotherapy, immunotherapy, HER2 targeted
             agents, and antitumor vaccines) for cancer, or radiation therapy for cancer

          -  Participants with a past history of ductal carcinoma in situ (DCIS) or lobular
             carcinoma in situ (LCIS) are not allowed to enter the study if they have received any
             systemic therapy for its treatment or radiation therapy to the ipsilateral breast
             (they are allowed to enter the study if treated with surgery alone)

          -  High-risk participants who have received chemopreventive drugs in the past are not
             allowed to enter the study

          -  Inadequate bone marrow, renal, or liver function

          -  History or evidence of cardiovascular condition

          -  Dyspnea at rest or other diseases that require continuous oxygen therapy

          -  Severe, uncontrolled systemic disease

          -  Participants with poorly controlled diabetes or with evidence of clinically
             significant diabetic vascular complications

          -  Pregnancy or breast-feeding women

          -  Participants who received any investigational treatment within 4 weeks of study start

          -  Participants with known infection with human immunodeficiency virus (HIV), hepatitis B
             virus, or hepatitis C virus

          -  Current chronic daily treatment with corticosteroids (dose >10 mg methylprednisolone
             or equivalent [excluding inhaled steroids])

          -  Known hypersensitivity to any of the study drugs or excipients
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of Participants With New York Heart Association (NYHA) Class III and IV Heart Failure During the Neoadjuvant Treatment Period
Time Frame:Baseline to 24 weeks
Safety Issue:
Description:Symptomatic left ventricular systolic dysfunction (LVSD) is defined as heart failure. NYHA classifies participants' heart failure condition based on the participant's symptoms. Class III: marked limitation of the physical activity. Comfortable at rest. Less than ordinary activity causes fatigue, palpitation, or dyspnea. Class IV: Unable to carry on any physical activity without discomfort. Symptoms of heart failure at rest. If any physical activity is undertaken, discomfort increases. 95 percent (%) confidence intervals (CIs) are calculated with the use of the Clopper-Pearson method.

Secondary Outcome Measures

Measure:Percentage of Participants With NYHA Class III and IV Heart Failure During the Adjuvant Treatment Period at Primary Completion Date (03 March 2016)
Time Frame:Cycle 9 to Cycle 21 (cycle length=3 weeks; up to approximately 8 months) up to clinical cut-off date, 03 March 2016 (Month 20)
Safety Issue:
Description:LVSD is defined as heart failure. NYHA classifies participants' heart failure condition based on the participant's symptoms. Class III: marked limitation of the physical activity. Comfortable at rest. Less than ordinary activity causes fatigue, palpitation, or dyspnea. Class IV: Unable to carry on any physical activity without discomfort. Symptoms of heart failure at rest. If any physical activity is undertaken, discomfort increases. 95% CIs was calculated with the use of the Clopper-Pearson method.
Measure:Percentage of Participants With Drop in LVEF of at Least 10 Points From Baseline and to Below 50% During the Adjuvant Treatment Period at Primary Completion Date (03 March 2016)
Time Frame:Cycle 9 to Cycle 21 (cycle length=3 weeks; up to approximately 8 months) up to clinical cut-off date, 03 March 2016 (Month 20)
Safety Issue:
Description:A confirmed event was defined as at least two consecutive readings of declines in LVEF. 95% CIs was calculated with the use of the Clopper-Pearson method.
Measure:Percentage of Participants With NYHA Class III and IV Heart Failure at the End of Study
Time Frame:Baseline up to approximately 6.5 years
Safety Issue:
Description:LVSD is defined as heart failure. NYHA classifies participants' heart failure condition based on the participant's symptoms. Class III: marked limitation of the physical activity. Comfortable at rest. Less than ordinary activity causes fatigue, palpitation, or dyspnea. Class IV: Unable to carry on any physical activity without discomfort. Symptoms of heart failure at rest. If any physical activity is undertaken, discomfort increases. 95% CIs will be calculated with the use of the Clopper-Pearson method.
Measure:Percentage of Participants With Drop in LVEF of at Least 10 Points From Baseline and to Below 50% at End of Study
Time Frame:Baseline up to approximately 6.5 years
Safety Issue:
Description:A confirmed event was defined as at least two consecutive readings of declines in LVEF. 95% CIs will be calculated with the use of the Clopper-Pearson method.
Measure:Percentage of Participants With Anti-Therapeutic Antibodies (ATAs) to Pertuzumab
Time Frame:Screening then prior to pertuzumab infusion (Hour 0) in Cycles 5, 14, 18 thereafter anytime between Cycle 8 Day 21 and surgery, up to treatment completion visit (cycle length=2-3 weeks; up to approximately 6.5 years)
Safety Issue:
Description:
Measure:Percentage of Participants With Total Pathological Complete Response (tpCR) Evaluated at the Time of Surgery Based on Local Pathologist's Assessment After Surgery
Time Frame:24 weeks after neoadjuvant therapy (Post 8 cycles of neo-adjuvant therapy [cycle length=2¬3 weeks])
Safety Issue:
Description:tpCR is defined as the absence of any residual invasive cancer in the breast and the absence of any metastatic cells in the regional lymph nodes.
Measure:Percentage of Participants With Clinical Response as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1 During the Neoadjuvant Treatment Period
Time Frame:Baseline until disease progression or death due to any cause up to 24 weeks (assessed on Day 1 of Cycles 1-8 [cycle length=2-3 weeks])
Safety Issue:
Description:Clinical response was classified as either complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD). CR: disappearance of all target lesions; PR: at least a 30% decrease in the sum of the longest diameter compared to Baseline. SD: neither sufficient shrinkage to qualify for PR nor sufficient (20%) increase to qualify for disease progression, in addition to no new target lesions. PD: at least a 20% increase in the sum of the longest diameter, taking as reference the smallest sum of the longest diameter observed at previous tumor assessment, or the appearance of any new lesions. 95% CIs are calculated with the use of the Clopper-Pearson method.
Measure:Event-Free Survival Determined by the Investigator According to RECIST v1.1
Time Frame:Baseline until disease progression or death due to any cause up to approximately 6.5 years (assessed on Day 1 of Cycles 1-8 [cycle length=2-3 weeks] and every 3 months thereafter until study completion or early termination)
Safety Issue:
Description:EFS is defined as the time from enrollment to the first occurrence of progressive disease, relapse, or death from any cause. PD: at least a 20% increase in the sum of the longest diameter, taking as reference the smallest sum of the longest diameter observed at previous tumor assessment, or the appearance of any new lesions.
Measure:Invasive Disease Free Survival (iDFS) Determined by the Investigator According to RECIST v1.1
Time Frame:Baseline until disease progression or death due to any cause up to approximately 6.5 years (assessed on Day 1 of Cycles 1-8 [cycle length=2-3 weeks] and every 3 months thereafter until study completion or early termination)
Safety Issue:
Description:iDFS is defined as the time from the first date of no disease (the date of surgery) to the first documentation of progressive invasive disease, relapse, or death. PD: at least a 20% increase in the sum of the longest diameter, taking as reference the smallest sum of the longest diameter observed at previous tumor assessment, or the appearance of any new lesions.
Measure:Overall Survival (OS)
Time Frame:Baseline up to death (approximately 6.5 years)
Safety Issue:
Description:OS was defined as the time from enrollment to death from any cause.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Hoffmann-La Roche

Last Updated

November 15, 2017