A Study Evaluating Perjeta (Pertuzumab) Combined With Herceptin (Trastuzumab) and Standard Anthracycline-based Chemotherapy in Patients With HER2-positive Locally Advanced, Inflammatory, or Early-stage Breast Cancer.

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Hoffmann-La Roche
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT02132949
First received: May 6, 2014
Last updated: August 26, 2014
Last verified: August 2014
  Purpose

This multicenter, non-randomized, open-label, phase II study is designed to eval uate the safety and efficacy of Perjeta in combination with Herceptin and anthra cycline-based chemotherapy as neoadjuvant treatment in patients with HER2-based locally advanced, inflammatory, or early-stage breast cancer. Each investigator will choose a treatment regimen (A or B) for all their patients to follow. Treat ment A (Cohort A): Patients will first be given doxorubicin (60 mg/m2 IV) and cy clophosphamide (600 mg/m2 IV). This will be followed by administration of paclit axel (80 mg/m2 IV), Perjeta (420 mg IV) and Herceptin (6 mg IV) for four cycles.

Treatment B (Cohort B): Patients will first receive 5-fluorouracil (500 mg/m2 I V), epirubicin (100 mg/m2 IV), and cyclophosphamide (600 mg/m2 IV). This is to b e followed by docetaxel (100 mg/m2 IV), Perjeta (420 mg IV) and Herceptin (6 mg IV) treatment for four cycles. Patients in both cohorts will subsequently underg

o surgical treatment and then resume Perjeta and Herceptin treatment. Total time on treatment is expected to last 1 year; patients will be followed-up for a fur ther 4 years.


Condition Intervention
Breast Cancer
Drug: 5-fluorouracil
Drug: cyclophosphamide
Drug: docetaxel
Drug: doxorubicin
Drug: epirubicin
Drug: paclitaxel
Drug: pertuzumab [Perjeta]
Drug: trastuzumab [Herceptin]

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multicenter, Multinational, Phase II Study to Evaluate Pertuzumab in Combination With Trastuzumab and Standard Neoadjuvant Anthracycline-based Chemotherapy in Patients With HER2-Positive, Locally Advanced, Inflammatory, or Early-Stage Breast Cancer

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Incidence of cardiac events as assessed by the investigator using National Cancer Institute (NCI) Common Terminology for Adverse Events (CTCAE) v. 4.0 [ Time Frame: Approximately 5 years ] [ Designated as safety issue: No ]
  • Changes in left ventricular ejection fraction assessed by ECHO or MUGA scan. [ Time Frame: Approximately 5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incidence of adverse events [ Time Frame: Approximately 5 years ] [ Designated as safety issue: No ]
  • Incidence of anti-therapeutic antibodies to Perjeta [ Time Frame: Approximately 5 years ] [ Designated as safety issue: No ]
  • Total pathological complete response defined as the eradication of invasive disease according to pathologist assessment [ Time Frame: Approximately 5 years ] [ Designated as safety issue: No ]
  • Clinical response as assessed by the investigator according to response evaluation criteria in solid tumors (RECIST) v. 1.1 [ Time Frame: Approximately 5 years ] [ Designated as safety issue: No ]
  • Event-free survival defined as time from enrollment to first occurrence of progressive disease, relapse, or death from any cause. [ Time Frame: Approximately 5 years ] [ Designated as safety issue: No ]
  • Invasive disease-free survival defined as the time from the first date of no disease to the first documentation of progressive invasive disease, relapse, or death from any cause. [ Time Frame: Approximately 5 years ] [ Designated as safety issue: No ]
  • Overall survival, defined as the time from enrollment to death from any cause. [ Time Frame: Approximately 5 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 400
Study Start Date: July 2014
Estimated Study Completion Date: February 2021
Estimated Primary Completion Date: February 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort A: ddAC -> T+PH Drug: cyclophosphamide
600 mg/m2 IV given every 2 weeks for 8 weeks (Cycles 1-4)
Drug: doxorubicin
60 mg/m2 IV given every 2 weeks for 8 weeks (Cycles 1-4)
Drug: paclitaxel
80 mg/m2 IV given weekly for 12 weeks (Cycles 5-8)
Drug: pertuzumab [Perjeta]
420 mg (840 mg first dose) IV given every 3 weeks for 17 cycles
Drug: trastuzumab [Herceptin]
6 mg/kg (8 mg/kg first dose) IV given every 3 weeks for 17 cycles
Experimental: Cohort B: FEC -> D+PH Drug: 5-fluorouracil
500 mg/m2 IV given every 3 weeks for 12 weeks (Cycles 1-4)
Drug: cyclophosphamide
600 mg/m2 IV given every 3 weeks for 12 weeks (Cycles 1-4)
Drug: docetaxel
100 mg/m2 (75 mg/m2 first dose) IV given every 3 weeks for 12 weeks (Cyles 5-8)
Drug: epirubicin
100 mg/m2 IV given every 3 weeks for 12 weeks (Cycles 1-4)
Drug: pertuzumab [Perjeta]
420 mg (840 mg first dose) IV given every 3 weeks for 17 cycles
Drug: trastuzumab [Herceptin]
6 mg/kg (8 mg/kg first dose) IV given every 3 weeks for 17 cycles

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age >/= 18 years
  • Male and female patients with locally advanced, inflammatory, or early-stage, unilateral, and histologically confirmed invasive breast cancer. Patients with inflammatory breast cancer must be able to have a core needle biopsy.
  • Primary tumor > 2 cm in diameter, or > 5 mm in diameter and node-positive
  • HER2-positive breast cancer confirmed by a central laboratory
  • Availability of tumor tissue specimen
  • Baseline left ventricular ejection fraction (LVEF) >/= 55%
  • Eastern Cooperative Oncology Group (ECOG) performance status </= 1
  • At least 4 weeks since major unrelated surgery, with full recovery
  • Use of effective contraception as defined by the protocol. Contraception must be used until at least 7 months after the last dose of study treatment.

Exclusion Criteria:

  • Metastatic disease (Stage IV) or bilateral breast cancer
  • Patients who have had an incisional biopsy of the primary tumor or the primary tumor excised
  • History of other malignancies within 5 years prior to study entry, except for carcinoma in situ of the cervix, carcinoma in situ of the colon, melanoma in situ, and basal cell and squamous cell carcinoma of the skin. Patients with malignancies occurring more than 5 years prior to study entry are permitted if curatively treated with surgery alone.
  • Any previous systemic therapy (including chemotherapy, immunotherapy, HER2 targeted agents, and antitumor vaccines) for cancer, or radiation therapy for cancer
  • Patients 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 patients who have received chemopreventative drugs in the past are not allowed to enter the study.
  • Inadequate bone marrow, renal, or liver function.
  • History or evidence of cardiovascular condition.
  • Any other concomitant serious medical condition, including infection with HIV, hepatitis B virus, or hepatitis C virus.
  • Pregnancy or breast-feeding.
  • Patients who received any investigational treatment within 4 weeks of study start
  • Current chronic daily treatment with corticosteroids (dose > 10 mg methylprednisolone or equivalent [excluding inhaled steroids]).
  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: NCT02132949

Contacts
Contact: Reference Study ID Number: WO29217 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. Only) global.rochegenentechtrials@roche.com

  Show 83 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

No publications provided

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02132949     History of Changes
Other Study ID Numbers: WO29217
Study First Received: May 6, 2014
Last Updated: August 26, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Cyclophosphamide
Fluorouracil
Trastuzumab
Pertuzumab
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites
Antimetabolites, Antineoplastic

ClinicalTrials.gov processed this record on September 16, 2014