Neoadjuvant Therapy in Clinical Stage I-III HER2-positive Breast Cancer.

NCT02789657 | Completed Phase 2 Results DMC

• 1 other identifier: BrUOG 308
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 2

Brief Summary

Neoadjuvant therapy is given to breast cancer patients whose cancers are relatively large or have spread to lymph nodes or both. The primary goal of this treatment is to prevent the cancer from coming back (recurring) elsewhere in the body, but if it makes the cancer in the breast and lymph nodes shrink it might be easier to remove. This could allow a patient to have a lumpectomy instead of a mastectomy and reduce the number of lymph nodes that the surgeon has to remove. In some cases, the neoadjuvant therapy works so well that it kills all of the cancer in the breast and lymph nodes. This is referred to as a pathologic complete response (pCR). Patients who achieve a pCR have a much lower risk of the cancer recurring elsewhere in their bodies. Investigators aren't sure which chemotherapy drugs work best with the HER2-targeted drugs, and what combination of these drugs causes the fewest side effects.Thus, this study has two main goals:

1. 1.To find out if treatment with wPCbTP, weekly paclitaxel and carboplatin given with trastuzumab and pertuzumab every 3 weeks, leads to as many pCRs as TCHP in patients with HER2-positive breast cancer, but has fewer side effects.
2. 2.To find out if HER2-positive patients whose cancers are not responding well after 12 weeks of wPCbTP get a better response when they are switched to a doxorubicin-containing regimen called AC for 4 cycles (8-12 weeks).

Conditions

Breast Cancer

Keywords

neoadjuvant breast cancer; stage I-III breast cancer; HER 2 positive breast cancer

Outcome Measures

Primary Outcomes (2)

• Percent of Patients Who Achieve a pCR

  pCR is pathologic complete response defined as ypT0/isN0 on pathology report

  at surgery post approximately 18 weeks of treatment

• Number of of Patients Who Develop Major Toxicities as Defined in Protocol.

  Defined based on CTCAE version 4: 1. Neutropenia (grade\>2) 2. Thrombocytopenia (grade \>2) 3. Anemia (grade \>2) 4. Diarrhea (any grade, grade \>3) 5. Neuropathy (any grade, grade 2, grade \>3) 6. Vomiting (any grade, grade \>3)

  From start of neo-adjuvant treatment through approximately 18 weeks.

Study Arms (4)

Optimal- 18 weeks

EXPERIMENTAL

18 weeks (6 cycles) of paclitaxel, carboplatin, trastuzumab and pertuzumab. Post treatment, patients will undergo surgery.

Drug: paclitaxel; Drug: Trastuzumab; Drug: Pertuzumab; Drug: carboplatin; Procedure: Breast surgery

Sub-optimal with AC

EXPERIMENTAL

12 weeks (4 cycles) of paclitaxel, carboplatin, trastuzumab and pertuzumab. Post 12 weeks, initiation of doxorubicin and cyclophosphamide for 4 cycles (6 weeks), followed by surgery.

Drug: paclitaxel; Drug: Trastuzumab; Drug: Pertuzumab; Drug: carboplatin; Procedure: Breast surgery; Drug: AC

Optimal with AC

EXPERIMENTAL

Less than 18 weeks (6 cycles) of paclitaxel, carboplatin, trastuzumab and pertuzumab, followed by initiation of doxorubicin and cyclophosphamide. Post treatment, patients will undergo surgery.

Drug: paclitaxel; Drug: Trastuzumab; Drug: Pertuzumab; Drug: carboplatin; Procedure: Breast surgery; Drug: AC

Sub-optimal no AC

EXPERIMENTAL

18 weeks (6 cycles) of paclitaxel, carboplatin, trastuzumab and pertuzumab. Post treatment, patients will undergo surgery.

Drug: paclitaxel; Drug: Trastuzumab; Drug: Pertuzumab; Drug: carboplatin; Procedure: Breast surgery

Interventions

paclitaxel DRUG

80 mg/m2 (or nab-paclitaxel 80-100 mg/m2) weekly

Also known as: taxel, onxal

Optimal with AC; Optimal- 18 weeks; Sub-optimal no AC; Sub-optimal with AC

Trastuzumab DRUG

Either every 3 weeks (8 mg/kg cycle 1 then 6 mg/kg cycles 2-4) or weekly (4 mg/kg week 1 then 2 mg/kg weeks 2-12)

Also known as: Herceptin

Optimal with AC; Optimal- 18 weeks; Sub-optimal no AC; Sub-optimal with AC

Pertuzumab DRUG

every 3 weeks (840 mg cycle 1 then 420 mg cycles 2-4) or weeks 1 and 2 cycle 1 (420 mg each dose) during the first 3-6 weeks of treatment, then 420 mg day 1 of cycles 2-4.

Also known as: Perjeta

Optimal with AC; Optimal- 18 weeks; Sub-optimal no AC; Sub-optimal with AC

carboplatin DRUG

AUC 2 administered weekly with no planned treatment breaks

Also known as: paraplatin

Optimal with AC; Optimal- 18 weeks; Sub-optimal no AC; Sub-optimal with AC

Breast surgery PROCEDURE

breast conserving or mastectomy

Optimal with AC; Optimal- 18 weeks; Sub-optimal no AC; Sub-optimal with AC

AC DRUG

doxorubicin and cyclophosphamide (AC) every 2 or 3 weeks for 4 cycles Dose-dense AC: Doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 IV day 1 every 2 weeks x 4 cycles Standard AC: Doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 IV day 1 r every 3 weeks x 4 cycles

Optimal with AC; Sub-optimal with AC

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed adenocarcinoma of the breast, with sufficient tissue available from needle or incisional biopsy (excisional biopsy not permitted) for ER, PR and HER2 testing.
• \. Resectable - clinical stage I (only with T=2.0 cm), IIA-IIIA - T2 N0-T3N0 or T1-3 N1-N2a - or unresectable - clinical stage IIIB-C - T4 or N2b-3 - disease. No evidence of M1 disease. Pretreatment clinical stage will be recorded by the treating physician.
• \. Breast tumor measuring at least 1 cm in greatest dimension by ultrasound or MRI; patients without measurable disease in the breast (TX) by imaging studies are eligible if they have measurable disease (a node measuring at least 1 cm along its short axis, and histologically confirmed to contain metastatic disease) in the axilla.
• \. HER2+, defined by either IHC 3+ or amplification of the HER2 gene by FISH analysis (ratio \>2.0 or \>6 HER2 targets per cell; patients with equivocal HER2 testing, 2+ by IHC with a FISH ratio of \<2.0 and 4-6 HER2 signals per nucleus, are not eligible).
• \. Patients with multiple foci of invasive cancer in the same breast are eligible if any single lesion meets the above size criteria and all sampled lesions \> 1 cm in maximum dimension are histologically similar and HER2+. Patients are also eligible , or if there is a focus of HER2- invasive cancer that is \<1 cm in maximum dimension and in a different quadrant of the breast from the HER2+ cancer, such that its presence will not interfere with clinical or pathologic assessment of response of the HER2+ cancer. The presence of DCIS or LCIS in either breast will not render a patient ineligible. Patients with a small focus of invasive cancer detected in the contralateral breast (clinical T1a/bN0) are eligible, whether the contralateral tumor is HER2+ or HER2-, while patients with a more advanced invasive cancer in the contralateral breast are not eligible; in patients with a small focus of invasive cancer in the contralateral breast or a small focus of HER2- cancer in the same breast only the histologic response in the HER2+ target lesion will be considered in determining the patient's pathologic response.
• It is recommended that patients have a pretreatment echocardiogram or MUGA scan with an LVEF above the institutional lower limit of normal.
• \. Female, age \>18, Zubrod PS 0-1. 8. It is recommended that patients have adequate bone marrow, renal and hepatic function. Examples of this include: ANC \> 1000/ul, platelet count \>100,000/ul, HGB\> 9.0 g/dl, serum creatinine \<1.5 mg/dl or measured creatinine clearance of \>30 ml/min and AST \<5 x ULN.
• \. Signed informed consent.

You may not qualify if:

• Prior chemotherapy, hormonal therapy, or radiation therapy for this cancer
• Patients with myocardial infarction, stroke or arterial thrombotic event within the past 12 months are not eligible.
• Pregnant and lactating women are not eligible. All patients of reproductive potential should have a negative pregnancy test at baseline and be advised to use an effective barrier method of contraception if sexually active during treatment on the study and for 2 months post the last treatment. Sites will be asked to confirm the patient's menopausal status at study entry and that premenopausal women had a negative pregnancy test performed within 7 days of starting treatment, but will not be required to submit test results.
• Active (defined as symptomatic, currently requiring treatment or likely to require treatment within the 6 months following study enrollment, or likely to affect the efficacy or tolerability of the study treatment) non-breast malignancy.
• Baseline grade \>2 peripheral neuropathy

Sponsors & Collaborators

• Brown University: lead
• Women and Infants Hospital of Rhode Island: collaborator
• Rhode Island Hospital: collaborator
• The Miriam Hospital: collaborator

Study Sites (2)

Rhode Island Hospital and The Miriam Hospital

Providence, Rhode Island, 02903, United States

Location

Women and Infants hospital of RI

Providence, Rhode Island, 02905, United States

Location

Related Publications (1)

• Lopresti ML, Bian JJ, Sakr BJ, Strenger RS, Legare RD, Fenton M, Witherby SM, Dizon DS, Pandya SV, Stuckey AR, Edmondson DA, Gass JS, Emmick CM, Graves TA, Cutitar M, Olszewski AJ, Sikov WM. Neoadjuvant weekly paclitaxel and carboplatin with trastuzumab and pertuzumab in HER2-positive breast cancer: a Brown University Oncology Research Group (BrUOG) study. Breast Cancer Res Treat. 2021 Aug;189(1):93-101. doi: 10.1007/s10549-021-06266-9. Epub 2021 Jun 4.

  PMID: 34086171 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Paclitaxel; Trastuzumab; pertuzumab; Carboplatin; Mastectomy, Segmental

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Coordination Complexes; Mastectomy; Surgical Procedures, Operative

Results Point of Contact

• Title: Brown University Oncology Research Group
• Organization: BrUOG

BrUOG@Brown.edu

4018633000

Study Officials

• Howard Safran, MD

  BrUOG Study Chair

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 30, 2016
• First Posted: June 3, 2016
• Study Start: November 21, 2016
• Primary Completion: November 14, 2019
• Study Completion: March 27, 2020
• Last Updated: May 19, 2022
• Results First Posted: April 28, 2022

Record last verified: 2022-04

Locations

US (2)