Neoadjuvant Hormonal Therapy Combined With Chemoimmunotherapy (Neohttp)

Neoadjuvant Hormonal Therapy Combined With Chemoimmunotherapy (Taxotere, Trastuzumab and Pertuzumab) in Patients With HER2-positive and ER-Positive Breast Cancer (NeoHTTP Study)

Hormonal therapy administered before surgery in ER-positive and HER2-positive patients with breast cancer.

Study Overview

• Status: Terminated
• Conditions: HER2-positive Breast Cancer; ER-positive Breast Cancer
• Intervention / Treatment: Drug: fulvestrant 500 mg; Drug: Docetaxel; Drug: Trastuzumab (H, 8mg/kg; Drug: Pertuzumab (P, 840 mg

Detailed Description

Hormonal therapy with fulvestrant 500 mg to be administered before surgery With docetaxel, Trastuzumab, and pertuzumab to determine pathological complete remission rate at the time of surgery in ER-positive and HER2-positive patients with breast cancer.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Goodyear, Arizona, United States, 85338
      • Western Regional Medical Center, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients ≥ 18 years of age with histologically, and radiographically confirmed non-metastatic ER-positive (defined as ≥30% of positive cells) and HER2-positive (defined as overexpression by immunohistochemistry (3+) or 2+ and positive by defined by fluorescence or dual in situ hybridization.) breast cancer with minimal tumor size over 2 cm (≥T2 lesion) to receive neoadjuvant chemotherapy recommended by the treating physician
2. Eastern Cooperative Oncology Group (ECOG) performance status score < 1
3. Absolute neutrophil count > 1500 mm3, platelet count ≥ 100×109 L, hemoglobin ≥ 8.5 g/dL
4. Serum creatinine ≤1.5 times the upper limit of the normal range, total bilirubin ≤ 1.5 X ULN (≤ 3 mg/dL if clinically diagnosed with Gilbert syndrome) AST/ALT ≤ 2.5 X ULN (AST/ALT ≤ 5X ULN if clinically diagnosed with Gilbert syndrome)
5. Women of child-bearing potential (i.e., women who are pre-menoposaul or not surgically sterile) must have a negative serum pregnancy test within 2 weeks prior to beginning treatment

Exclusion Criteria:

1. Uncontrolled cardiac disease, such as angina, hypertension or significant arrhythmias
2. LVEF (left ventricular ejection fraction) < 50% on any prior assessment. Note: Assessment of LVEF is done before and after trastuzumab-based chemotherapy as standard of care
3. Pregnant or lactating females
4. Inability to complete informed consent process and adhere to the protocol treatment plan and follow-up requirements
5. Concurrent severe illness such as active infection, or psychiatric illness/social situations that would limit safety and compliance with study requirements

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment Protocol; Hormonal therapy with fulvestrant 500 mg will be administered intramuscularly on days 1, 15 of the first cycle, and thereafter on day 1 of every 28-day cycle for up to 5 cycles before surgery. Docetaxel (T) 75 mg/m2 every 3 weeks will be given for four cycles. Trastuzumab (H, 8mg/kg for 1st cycle, then 6 mg/kg in subsequent cycles before and after surgery), pertuzumab (P, 840 mg for 1st cycle, then 420 mg in subsequent 3 cycles) will be given concurrently with docetaxel for a total of 4 cycles before surgery.

Drug: fulvestrant 500 mg; Hormonal therapy with fulvestrant 500 mg will be administered intramuscularly on days 1, 15 of the first cycle, and thereafter on day 1 of every 28-day cycle for up to 5 cycles before surgery.; Other Names: fulvestrant; Drug: Docetaxel; Docetaxel (T) 75 mg/m2 every 3 weeks will be given for four cycles.; Other Names: Taxotere; Drug: Trastuzumab (H, 8mg/kg; Trastuzumab (H, 8mg/kg for 1st cycle, then 6 mg/kg in subsequent cycles before and after surgery), pertuzumab (P, 840 mg for 1st cycle, then 420 mg in subsequent 3 cycles) will be given concurrently with docetaxel for a total of 4 cycles before surgery.; Other Names: Trastuzumab; Drug: Pertuzumab (P, 840 mg; Trastuzumab (H, 8mg/kg for 1st cycle, then 6 mg/kg in subsequent cycles before and after surgery), pertuzumab (P, 840 mg for 1st cycle, then 420 mg in subsequent 3 cycles) will be given concurrently with docetaxel for a total of 4 cycles before surgery.; Other Names: Pertuzumab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological Complete Remission Rate	To determine pathological complete remission rate at the time of surgery in ER-positive and HER2-positive breast cancer patients undergoing neoadjuvant chemoimmunotherapy (docetaxel, trastuzumab, pertuzumab) concurrently with neoadjuvant hormonal therapy with fulvestrant. Note: pCR, defined as the absence of invasive neoplastic cells of the primary tumor in the breast, remaining in-situ lesions are allowed, ypT0-is;	one year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Partial Pathological Response Rate	Partial pathological response rate at the time of surgery and biomarker changes in breast cancer (biopsy vs residual tumor) before and after neoadjuvant chemotherapy Note: pPR, defined as residual invasive disease of 1cm, ypT1a-b.	One Year
QTA (Quantitative Texture Analysis)	QTA (Quantitative Texture Analysis): will be obtained from baseline mammogram and the correlation with clinical outcome after neoadjuvant therapy will be performed.	One year

Collaborators and Investigators

• Sponsor: Western Regional Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2014
• Primary Completion (Actual): November 1, 2015
• Study Completion (Actual): November 1, 2015

Study Registration Dates

• First Submitted: January 19, 2015
• First Submitted That Met QC Criteria: January 23, 2015
• First Posted (Estimate): January 26, 2015

Study Record Updates

• Last Update Posted (Actual): February 20, 2018
• Last Update Submitted That Met QC Criteria: January 22, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Immunological; Hormone Antagonists; Estrogen Antagonists; Estrogen Receptor Antagonists; Docetaxel; Trastuzumab; Fulvestrant; Pertuzumab
• Other Study ID Numbers: WIRB 20140462

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No