Pertuzumab and Trastuzumab as Neoadjuvant Treatment in Patients With HER2-Positive Breast Cancer

Breast Cancer Clinical Trial

Official title:

A Phase 2 Clinical Trial Assessing the Correlation of Early Changes in Standardized Uptake Value (SUV) on Positron Emission Tomography (PET) With Pathological Complete Response (pCR) to Pertuzumab and Trastuzumab in Patients With Primary Operable HER2-Positive Breast Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01937117
• Other study ID #: TBCRC 026
• Secondary ID: TBCRC026NA_00080
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: January 30, 2014
• Est. completion date: May 2025

Study information

• Verified date: February 2024
• Source: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This research is being done to determine if early changes on a type of imaging procedure called PET (Positron Emission Tomography) can predict which patients are most likely to respond to the combination of trastuzumab and pertuzumab when given prior to surgery.

Description:

This study will evaluate for the first time the correlation between early changes in SUV and pCR in men and women with ER-negative, human epidermal growth factor receptor 2 (HER2)-positive breast cancer receiving trastuzumab and pertuzumab (PT) pre-operatively. This has not previously been evaluated in patients receiving anti HER2 therapy alone and as such is novel and potentially practice changing. The results from this phase 2 biomarker study will be used to plan a randomized study using a predefined cut point for SUV decline such that the investigators can further attempt to identify a group of individuals with HER2-positive early breast cancer who do not require cytotoxic chemotherapy in addition to anti-HER2 agents. This non-invasive biomarker approach will be of great interest to breast cancer oncologists and patients by facilitating a personalized approach to managing patients with HER2-positive disease that will undoubtedly spare toxicity and reduce the costs associated with anti-cancer strategies, without compromising efficacy.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 88
• Est. completion date: May 2025
• Est. primary completion date: March 20, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Female and male patients, 18 years old or older

• Histologically proven infiltrating carcinoma of the breast on core needle biopsy that is: estrogen receptor (ER)/progesterone receptor (PR) =10% staining by immunohistochemistry (IHC) and HER2 positive - IHC 3+, in situ hybridization (ISH) =2.0, or average HER2 copy number =6.0 signals per cell or per current American Society of Clinical Oncology - College of American Pathologists (ASCO-CAP) or National Comprehensive Cancer Network (NCCN) guidelines. Note: All histological diagnostic material should be reviewed at enrolling institution as required per local standards.

• Unresected, untreated breast cancer that meets one of the following clinical stages (see Appendix A): T2, T3, or T4a-c lesion, any N, M0. Note: Patients with inflammatory breast cancer (T4d) are not eligible. Bilateral cancers are permitted with approval of the Protocol Chair.

• Eastern Cooperative Oncology Group (ECOG) performance status 0-1 (Appendix B)

• Adequate organ function as follows:

1. Absolute neutrophil count (ANC) = 1,500/mm3

2. Platelet count = 100,000/mm3

3. Hemoglobin = 10 g/dL

4. Creatinine = 1.5 times the upper limit of normal with creatinine clearance = 50 mL/min using the Modified Cockcroft-Gault method

5. Bilirubin (total) = 1.5 times upper limit normal (with exception of Gilberts syndrome)

6. AST(SGOT), ALT(SGPT), and alkaline phosphatase = 2 times the upper limit of normal

• Adequate cardiac function as defined by left ventricular ejection fraction (LVEF) = 50% on echocardiogram or multi-gated acquisition scan (MUGA)

• Able and amenable to baseline and follow-up PET/CT imaging and study-specific biopsy procedures. Note: If there are any imaging concerns that the patient may not be suitable for quantitative PET/CT (e.g., a metallic device directly overlies the breast), discussion with the local and central radiologists is required to confirm eligibility for the trial. Also, it is expected that subjects have all PET/CT imaging done on pre-qualified machines for the study; if baseline imaging done on another machine, please contact the Protocol Chair/designee for guidance prior to confirming eligibility.

• The patient, if of childbearing potential, is willing to use effective, non-hormonal contraception while on treatment and for at least 6 months following the last dose of therapy.

• Patient understands the study regimen, its requirements, risks, and discomforts, and is able and willing to sign an informed consent form.

Exclusion Criteria:

• Received prior or ongoing local (e.g radiation) or systemic treatment (chemotherapy or endocrine therapy) for the current breast cancer. Patients who received tamoxifen or raloxifene or another agent for prevention of breast cancer may be included as long as the patient has discontinued the treatment at least one month prior to baseline study biopsy.

• Systemic treatment for prior cancer within the last 5 years, with the exception of adequately treated cone-biopsied in situ carcinoma of the cervix uteri and basal or squamous cell carcinoma of the skin.

• Women who are pregnant or nursing

• Current use of any investigational agents

• Known hypersensitivity to trastuzumab or pertuzumab

• Any medical condition that in the opinion of the investigator puts the patient at risk of potentially serious complications while on this therapy. Specifically, uncontrolled hypertension (systolic >150 and/or diastolic >100), unstable angina, congestive heart failure of any New York Heart Association (NYHA) classification, serious cardiac arrhythmia requiring treatment (exception: atrial fibrillation, paroxysmal supraventricular tachycardia), history of myocardial infarction within 6 months of enrollment.

Related Conditions & MeSH terms

• Breast Cancer
• Breast Neoplasms

Intervention

Procedure:
• Positron emission tomography (PET)
PET will be performed at baseline and on day 15

Drug:
• Trastuzumab
8 mg/kg loading dose, then 6 mg/kg every 3 weeks, IV
• Pertuzumab
840 mg as a loading dose, then 420 mg every 3 weeks, IV

Locations

Country	Name	City	State
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	University of Alabama Comprehensive Cancer Center	Birmingham	Alabama
United States	Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	Baylor College of Medicine	Houston	Texas
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	Indiana University Simon Cancer Center	Indianapolis	Indiana
United States	Vanderbilt University	Nashville	Tennessee
United States	Mayo Clinic	Rochester	Minnesota
United States	Fred Hutchinson Cancer Research Center - University of Washington	Seattle	Washington
United States	Johns Hopkins Kimmel Cancer Center at Sibley Memorial Hospital	Washington	District of Columbia

Sponsors (3)

Lead Sponsor	Collaborator
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Genentech, Inc., Translational Breast Cancer Research Consortium

Country where clinical trial is conducted

United States, 

References & Publications (1)

Connolly RM, Leal JP, Solnes L, Huang CY, Carpenter A, Gaffney K, Abramson V, Carey LA, Liu MC, Rimawi M, Specht J, Storniolo AM, Valero V, Vaklavas C, Krop IE, Winer EP, Camp M, Miller RS, Wolff AC, Cimino-Mathews A, Park BH, Wahl RL, Stearns V. TBCRC026 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Change in Standardized Uptake Value (SUV) as Measured by SULmax on [18F]Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET)	SULmax is the maximum SUV corrected for lean body mass. Change in SULmax from baseline to Day 15 on FDG PET in correlation with pathological complete response (pCR) in patients treated with preoperative pertuzumab/trastuzumab. pCR was defined as no viable invasive cancer in breast and axilla by local pathology review. SULmax was measured via spherical volume over the target primary breast cancer tissue.	Baseline and Day 15
Secondary	Change in ptDNA With Response	To correlate PIK3CA mutation status and other genomic alterations (mutations/somatic rearrangements) qualitatively and quantitatively in plasma tumor DNA (ptDNA) with pCR	2 years
Secondary	Change in PI3K Pathway Activation With Response	To correlate PI3K pathway activation (e.g. PTEN low and/or PIK3CA mutation, human epidermal growth factor receptor (HER) 1-4 expression and/or phosphorylation) in tumor samples and pCR	2 years
Secondary	Changes in Ki67 With Response	To correlate baseline and change (day 15) in Ki67 with pCR	2 years