Breast Cancer, HER2-positive Breast Cancer
Conditions
Keywords
HER2-positive early breast cancer, invasive breast carcinoma, zanidatamab, breast neoplasm
Brief summary
The purpose of this study is to see if zanidatamab is safe and effective, when combined with chemotherapy, in treating people who has Human Epidermal Growth Factor Receptor 2 (HER2)-positive, early-stage breast cancer
Interventions
DRUGZanidatamab
Administered intravenously (IV)
DRUGPaclitaxel
Administered intravenously (IV)
DRUGDocetaxel
Administered intravenously (IV)
DRUGCarboplatin
Administered intravenously (IV)
DRUGTrastuzumab
Administered intravenously (IV)
DRUGPertuzumab
Administered intravenously (IV)
Sponsors
Jazz Pharmaceuticals
Jazz Pharmaceuticals Ireland Limited
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Has newly diagnosed Stage II or III histologically confirmed invasive breast carcinoma. 2. Has histologically confirmed HER2-positive breast cancer 3. Has a known hormone receptor (HR) status of the primary tumor 4. Participants with multifocal or multicentric disease are eligible if the largest tumor (which must be larger than or equal to 2 cm in diameter) is HER2-positive, and the treating physician has determined the participant should be treated as HER2-positive. 5. Agrees to undergo a mastectomy or breast conserving surgery (BCS) after neoadjuvant therapy. 6. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 7. Adequate organ function 8. Has an LVEF ≥ 50% as determined by either ECHO or MUGA obtained within 6 weeks prior to randomization. 9. Adequate contraceptive precautions 10. Participants with known HIV are eligible unless: 1. CD4+ T Cell count is less than or equal to 350 microliters (uL) 2. Detectable viral load, or 3. Receiving protease inhibitors or cobicistat
Exclusion criteria
1. Has Stage IV (metastatic) breast cancer. 2. Has bilateral breast cancer. 3. Has a history of any severe and/or uncontrolled medical conditions or other conditions that, in the opinion of the investigator, could affect the participant's involvement in the study. 4. Has uncontrolled hypertension 5. Has significant symptoms from peripheral neuropathy 6. Has an active uncontrolled infection 7. Has a history of life-threatening hypersensitivity to monoclonal antibodies or to recombinant proteins or excipients in the drug formulation of zanidatamab or other study interventions. 8. Known active hepatitis B or C infection. 9. Has another malignancy diagnosed within the last 5 years. Exceptions include previously treated non melanomatous skin cancers, carcinoma in-situ, and melanoma in-situ. Participants with prior ipsilateral ductal carcinoma in situ (DCIS) or invasive breast cancer are not eligible. 10. Was treated with surgery, chemotherapy, anti-HER2 therapy, radiation therapy, endocrine therapy, or experimental therapy for invasive breast cancer 11. Is planning to receive concurrent therapy with any other investigational agent or anti-cancer therapy not specified in the protocol 12. Receipt of a live vaccine within 4 weeks prior to enrollment 13. Has a known hypersensitivity to any components of the study interventions, including chemotherapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with pCR | Up to 8 months | Pathologic complete response (pCR) is defined as lacking all signs of cancer in the tissue samples removed in the breast or axilla (armpit) during surgery or biopsy after study treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with Pathologic response by Residual Cancer Burden (RCB) classification | Up to 8 months | — |
| Number of Participants with Treatment-emergent Adverse Events (TEAEs) | Up to 23 months | — |
| Number of Participants Discontinuing Study Treatment Due to TEAEs | Up to 23 months | — |
| Number of participants that completed breast conservation surgery (BCS) | Up to 8 months | — |
| Event Free Survival (EFS) | Up to 46 months | EFS is defined as the time (in months) from randomization to disease progression, disease recurrence, second primary invasive cancer (non-breast) or death from any cause |
| Overall Survival (OS) | Up to 46 months | OS is defined as the time in months from randomization to the date of death due to any cause. |
| Number of participants reporting Symptomatic Adverse Events based on Patient-reported Outcome-Common Terminology Criteria for AEs (PRO-CTCAE) | Up to 23 months | Symptomatic AEs assessed by the PRO-CTCAE are analyzed at the item level with symptom severity, frequency, and interference scored from 0 to 4 and presence/absence scored 0 to 1, and higher scores reflect worse symptoms. |
| Number of participants reporting Symptomatic Adverse Events based on European Organisation for Research and Treatment of Cancer (EORTC) Item Library | Up to 23 months | Symptomatic AEs assessed by the EORTC Item Library Forms are analyzed at the item level with scores ranging from 1 to 4, where a 4 indicates more severe symptoms. |
| Percentage of all treated participants reporting overall side-effect bother on the Functional Assessment of Chronic Illness Therapy General Physical Item 5 (FACIT-GP5) | Up to 23 months | The Functional Assessment of Chronic Illness Therapy (FACIT) GP5 Item score ranges from 0 (Not at all) to 4 (Very Much), where higher scores reflect greater bother from treatment side effects. |
| Serum Concentrations of Zanidatamab | Up to 18 months | — |
| Number of Participants Positive for Anti-drug Antibodies to Zanidatamab | Up to 18 months | — |
Countries
Italy, Spain, United States
Contacts
CONTACTClinical Trial Disclosure & Transparency
Outcome results
None listed