DAPHNe: Paclitaxel/Trastuzumab/Pertuzumab in HER2-Positive BC

Breast Cancer Clinical Trial

Official title:

DAPHNe: De-escalation to Adjuvant Antibodies Post-pCR to Neoadjuvant THP (Paclitaxel/Trastuzumab/Pertuzumab)-a Pilot Study in HER2-positive Breast Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03716180
• Other study ID #: 18-394
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: November 5, 2018
• Est. completion date: September 1, 2030

Study information

• Verified date: September 2023
• Source: Dana-Farber Cancer Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This research study is studying whether participants and their doctors are willing to determine post-surgery treatment on the basis of response to pre-surgery treatment, and studying blood and tissue collected from participants treated with a combination of drugs as a treatment for breast cancer.

The names study drugs involved in this study are:

• Paclitaxel (also called Taxol)

• Trastuzumab (also called Herceptin)

• Pertuzumab (also called Perjeta)

Description:

This research study is a Pilot Study, which means investigators are looking at the feasibility of a new approach for deciding the optimal medical treatment for this type of breast cancer. The FDA (the U.S. Food and Drug Administration) has approved paclitaxel, trastuzumab, and pertuzumab as part of a pre-operative treatment option for this disease.

The purpose of this study is to evaluate whether participants and their doctors are willing to accept a treatment recommendation for post-operative chemotherapy, on the basis of the participant's response to pre-operative treatment with paclitaxel, trastuzumab, and pertuzumab.

In addition, the investigators are evaluating how the body's immune system works with paclitaxel, trastuzumab, and pertuzumab to kill cancer cells. For this reason, the investigators will collect samples of the participant's breast tumor and samples of the participant's blood over time to understand the reaction of the immune system to the participant's tumor.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 100
• Est. completion date: September 1, 2030
• Est. primary completion date: October 8, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patients must have Stage II or III (according to AJCC cancer staging manual anatomic staging table, 8th edition) histologically confirmed invasive carcinoma of the breast. A minimum tumor size of 1.5 cm determined by physical exam or imaging (whichever is larger) is required. Patients with inflammatory breast carcinoma (T4d) are NOT eligible.

• Tumors must be HER-2 positive, as assessed by standard local institutional protocol (central testing is not required):

• IHC 3+

• FISH positive based on one of the three following criteria:

Single-probe average HER2 copy number = 6.0 signals/cell; OR

• Dual-probe HER2/CEP17 ratio <2.0 with an average HER2 copy number = 6.0 signals/cell; OR

• Dual-probe HER2/CEP17 ratio =2.0

• ER/PR determination is required. ER- and PR-assays should be performed by immunohistochemical methods according to the local institution standard protocol.

• Bilateral breast cancers are allowed as long as both cancers are HER2-positive (as defined in 3.1.2), or the contralateral cancer is a <1 cm, ER+, and HER2- tumor.

• Patients with multifocal or multicentric disease are eligible as long as all tumor foci that were tested for HER2 status at the local institution are HER2-positive, and at least one tumor focus meets eligibility criteria.

• Breast imaging should include dedicated ultrasound of the ipsilateral axilla. For subjects with a clinically positive axilla based on exam or imaging, a fine needle aspiration or core biopsy procedure will be performed to determine the presence of metastatic disease in the lymph nodes (though lymph node sampling procedure need not be resulted prior to patient's registration on trial, as long as all other eligibility are met).

• Men and women (with any menopausal status) = 18 years of age are eligible.

• ECOG PS 0 or 1.

• Required laboratory values:

• ANC = 1000/mm3

• Hemoglobin = 9 g/dl

• Platelets = 100,000/mm3

• Serum creatinine < 1.5 x ULN (institutional) OR calculated GFR =60mL/min.

-Total bilirubin = 1.5 x ULN (institutional). For patients with Gilbert Syndrome, the direct bilirubin should be within the institutional normal range OR total bilirubin = 2.0 mg/dL.

• AST and ALT = 2.5x ULN (institutional)

• Left ventricular ejection fraction (LVEF) = 50%.

• Premenopausal women must have a negative serum pregnancy test within 14 days of registration, including women who have had a tubal ligation and for women less than 12 months after the onset of menopause.

• Women of childbearing potential and men with partners of childbearing potential must be willing to use one highly effective form of non-hormonal contraception or two effective forms of non-hormonal contraception by the patient and/or partner and continue its use for the duration of the study treatment and for 7 months after the last dose of study treatment.

• Patients with a history of ipsilateral DCIS are eligible.

• Patients undergoing breast conservation therapy (i.e. lumpectomy) must not have any contraindications to radiation therapy.

• Willing and able to sign informed consent.

• Willing to provide tissue for research purposes

Exclusion Criteria:

• Pregnant or nursing women due to the teratogenic potential of the study drugs.

• Active, unresolved infection.

• Receipt of intravenous antibiotics for infection within 7 days prior to registration.

• Uncontrolled hypertension (systolic >180 mm Hg and/or diastolic >100 mm Hg) or clinically significant (i.e. active) cardiovascular disease: cerebrovascular accident/stroke or myocardial infarction within 6 months prior to first study medication, unstable angina, congestive heart failure (CHF) of New York Heart Association (NYHA) Class II or higher (see Appendix B), or serious cardiac arrhythmia requiring medication.

• Significant symptoms (Grade = 2) from peripheral neuropathy.

• Other concurrent serious diseases that may interfere with planned treatment, including severe pulmonary conditions/illness, uncontrolled infections, uncontrolled diabetes.

• Any prior treatment for the current breast cancer, including chemotherapy, hormonal therapy, radiation, or experimental therapy

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Drug:
• Paclitaxel
Paclitaxel is an anti-cancer ("antineoplastic" or "cytotoxic") chemotherapy drug
• Trastuzumab
Trastuzumab works by targeting the HER2/neu receptor on cancer cells
• Pertuzumab
Pertuzumab is a monoclonal antibody which targets the surface of the cells human epidermal growth factor receptor 2 protein (HER2) on the cancer cell, interfering with HER2 causing cancer cell death

Locations

Country	Name	City	State
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	DF/BWCC at Milford Regional Medical Center	Milford	Massachusetts
United States	DF/BWCC in clinical affiliation with South Shore Hospital	South Weymouth	Massachusetts

Sponsors (4)

Lead Sponsor	Collaborator
Dana-Farber Cancer Institute	Breast Cancer Research Foundation, Susan G. Komen Breast Cancer Foundation, Terri Brodeur Breast Cancer Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adjuvant chemotherapy Received	To assess adherence to protocol-specified antibody doublet therapy in the adjuvant setting among patients with stage II-III HER2+ breast cancer who achieve pathologic complete response (pCR) following neoadjuvant Paclitaxel/Trastuzumab/Pertuzumab (THP).	2.5 years
Secondary	pCR rate	To assess pathologic complete response (pCR) for 1) all patients, 2) hormone receptor positive (HR+) patients, and 3) hormone receptor negative (HR-) patients	2 years
Secondary	Residual Cancer Burden (RCB) scores	To assess residual cancer burden (RCB) in 1) all patients, 2) hormone receptor positive patients (HR+), 3) hormone receptor negative (HR-) patients. RCB is scored from 0 to 3, (with possible values 0, 1, 2, 3), where 0 is the best score and indicates eradication of all disease at the time of surgery, and 3 is the worst score, indicating poor response to preoperative therapy.	2 years
Secondary	Reasons for Off-Protocol Escalation per study-specific questionnaires	Patients and physicians will complete questionnaires to assess reasons for off-protocol escalation (meaning, a decision to administer post-operative chemotherapy, for patients with pCR). Standardized questionnaires for both patients and physician reviewers have been developed specifically for this study. Responses are qualitative and do not involve a scale.	2 years
Secondary	Reasons for Off-Protocol De-Escalation per study-specific questionnaires	Patients and physicians will complete questionnaires to assess reasons for off-protocol de-escalation (meaning, a decision not to administer post-operative chemotherapy, for patients without pCR). Standardized questionnaires for both patients and physician reviewers have been developed specifically for this study. Responses are qualitative and do not involve a scale.	2 years
Secondary	One Year of Trastuzumab and Pertuzumab	To assess the percentage of patients completing one year of HP	3 years
Secondary	Event-Free Survival (EFS)	To measure event-free survival (EFS), and to compare EFS in the following subgroups: 1) Patients with pCR versus patients without pCR; 2) Patients with RCB 0 or 1, versus patients with RCB 2 or 3	12 years
Secondary	Recurrence-Free Interval (RFI)	To measure recurrence-free interval (RFI), and to compare RFI in the following subgroups: 1) Patients with pCR versus patients without pCR; 2) Patients with RCB 0 or 1, versus patients with RCB 2 or 3	12 years
Secondary	Overall survival (OS)	To measure overall survival (OS) as an exploratory endpoint	12 years
Secondary	Post-THP (Paclitaxel/Trastuzumab/Pertuzumab) imaging findings and pathology findings in the surgical specimen	To evaluate correlation between post-THP (Paclitaxel/Trastuzumab/Pertuzumab) imaging findings and pathology findings in the surgical specimen	2 years