Trastuzumab and Pertuzumab or Bevacizumab With Combination Chemotherapy in Treating Patients With Stage II-III Breast Cancer

NCT01959490 | Completed Phase 2 Results DMC

• 4 other identifiers: CASE14112NCI-2013-01422CASE 14112P30CA043703
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well trastuzumab and pertuzumab or bevacizumab with combination chemotherapy works in treating patients with stage II-III breast cancer. Monoclonal antibodies, such as trastuzumab, pertuzumab, and bevacizumab, can block tumor growth in different ways. Some block the ability of tumors to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Drugs used in chemotherapy, such as docetaxel, carboplatin, doxorubicin hydrochloride, cyclophosphamide, and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving trastuzumab and pertuzumab or a commercially marketed formulation of bevacizumab without modification with combination chemotherapy may kill more tumor cells.

Conditions

Stage II Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Number of Patients With a Pathological Complete Response (pCR) Who Received Targeted Therapy With Trastuzumab and Pertuzumab or Bevacizumab Predicted by Genomically-derived Molecular Subtypes.

  Number of patients with a pathological complete response (pCR) who received targeted therapy with trastuzumab and pertuzumab or bevacizumab predicted by genomically-derived molecular subtypes (HER2 positive or HER2 negative. pCR is defined as absence of invasive cancer in breast or lymph nodes after neoadjuvant chemotherapy.

  Up to 30 days after last cycle of treatment

Secondary Outcomes (5)

• The Number of HER2 Positive Patients With a Pathological Complete Response (pCR) Predicted by a Trastuzumab and Pertuzumab Response Signature

  Up to 30 days after last cycle of treatment

• The Number of HER2 Negative Patients With a pCR Predicted by the TGF-B Response Signature

  Up to 30 days after last cycle of treatment

• The Number of HER2 Positive Patients With a pCR Predicted by the AKT Signature and IGF Signature.

  Up to 30 days after last cycle of treatment

• The Number of Patients With a pCR Predicated by Copy Number Alterations.

  Up to 30 days after last cycle of treatment

• The Number of Patients With a pCR Predicted by Changes in Texture on Breast DCE-MRI After a Two-week "run-in" Treatment With Trastuzumab, Pertuzumab, or Bevacizumab

  At 2 weeks after start of run-in period

Other Outcomes (1)

• Descriptive Statistics of PET/CT Scan

  Up to 30 days after last cycle of treatment

Study Arms (3)

Cohort 1P (HER2 positive)

EXPERIMENTAL

Patients receive a run-in Pertuzumab treatment of 840 mg IV over 60 minutes on day -14 followed by Trastuzumab IV over 30-60 minutes and Pertuzumab IV over 30-60 minutes, docetaxel IV, and carboplatin IV on day 1. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.

Biological: trastuzumab; Biological: Pertuzumab; Drug: docetaxel; Drug: carboplatin

Cohort 1T (HER2 positive)

EXPERIMENTAL

Patients receive a run-in Trastuzumab treatment of 8 mg/kg IV over 90 minutes on day -14 followed by Trastuzumab IV over 30-60 minutes and Pertuzumab IV over 30-60 minutes, Docetaxel IV, and Carboplatin IV on day 1. Treatment repeats every 3 weeks for 6 courses in the absence of disease progression or unacceptable toxicity.

Biological: trastuzumab; Biological: Pertuzumab; Drug: docetaxel; Drug: carboplatin

Cohort II (HER2 negative)

EXPERIMENTAL

Patients receive Bevacizumab IV over 30-60 minutes on day 1 of weeks 1, 3, 5, 7, 9, and 11; Doxorubicin IV and Cyclophosphamide IV over 30-60 minutes on day 1 of weeks 1, 3, 5, and 7; and Paclitaxel IV over 3 hours on day 1 of weeks 9, 11, 13, and 15.

Drug: doxorubicin; Drug: cyclophosphamide; Drug: paclitaxel; Drug: Bevacizumab

Interventions

trastuzumab BIOLOGICAL

Given IV

Also known as: anti-c-erB-2, Herceptin, MOAB HER2

Cohort 1P (HER2 positive); Cohort 1T (HER2 positive)

Pertuzumab BIOLOGICAL

Given IV

Also known as: 2C4, Perjeta

Cohort 1P (HER2 positive); Cohort 1T (HER2 positive)

docetaxel DRUG

Given IV

Also known as: RP 56976, Taxotere, TXT

Cohort 1P (HER2 positive); Cohort 1T (HER2 positive)

carboplatin DRUG

Given IV

Also known as: Carboplat, CBDCA, JM-8, Paraplat, Paraplatin

Cohort 1P (HER2 positive); Cohort 1T (HER2 positive)

doxorubicin DRUG

Given IV

Also known as: ADM, ADR, Adria, Adriamycin PFS, Adriamycin RDF, doxorubicin hydrochloride

Cohort II (HER2 negative)

cyclophosphamide DRUG

Given IV

Also known as: CPM, CTX, Cytoxan, Endoxan, Endoxana

Cohort II (HER2 negative)

paclitaxel DRUG

Given IV

Also known as: Anzatax, Asotax, TAX, Taxol

Cohort II (HER2 negative)

Bevacizumab DRUG

Also known as: Avastin

Cohort II (HER2 negative)

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 for estrogen receptor (ER), progesterone receptor (PR), and HER 2 testing
• HER2 must be positive by IHC or ISH testing by laboratory standard.
• Needle biopsy or incisional biopsy
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1
• Resectable disease-clinical stage I (T/0/N0miT1N0-N0mi), IIA-IIIA (T2 N0/T3N0 or T1-3 N1-N2a) or unresectable disease - clinical stage IIIB/IIIC (T4 or T1-3 N2b-3); no evidence of metastatic disease
• No prior chemotherapy, hormonal therapy, or radiation therapy for this cancer
• Absolute neutrophil count (ANC) ≥1000/ul
• Platelet count ≥ 100,000/ul
• Hemoglobin ≥ 9 g/dl
• Serum creatinine ≤ 1.5 mg/dl or measured creatinine clearance of \> 30 ml/min
• Total bilirubin ≤ upper limit of normal (ULN)
• Aspartate aminotransferase (AST) ≤ 2.5 x ULN
• 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 are histologically similar (whether radiographically detected lesions separate from the target lesion are sampled for histologic evaluation is left to the discretion of the treating physicians); the presence of ductal carcinoma in situ (DCIS) or lobular carcinoma in situ (LCIS) in either breast will not render a patient ineligible; patients with a small focus of invasive cancer detected the contralateral breast (clinical T1N0) are eligible, however only the histologic response in the breast containing the target lesions will be considered in determining the patient's pathologic response
• Measurable disease in the breast or axilla that measures at least 1 cm by either clinical or radiographic measurement

You may not qualify if:

• Excisional biopsy
• Pregnant and lactating women are not eligible; all participants of reproductive age must have a negative serum pregnancy test at baseline and agree to use an effective barrier method of contraception during the entire period of treatment on the study
• Patients with New York Heart Association (NYHA) grade 2 or higher congestive heart failure, myocardial infarction within the last 6 months, unstable angina pectoris, or arterial thrombotic event with the past 12 months, uncontrolled hypertension (systolic blood pressure \> 150 and/or diastolic blood pressure \> 100 on antihypertensive medications; patients not on medication for high blood pressure who are found to have systolic blood pressure \[SBP\] \> 150 and/or diastolic blood pressure \[DBP\] \> 100 should have 3 documented episodes of elevated blood pressure before being considered 'uncontrolled', if they have 3 documented episodes of elevated blood pressure, then can be started on antihypertensive medications; patients currently on antihypertensive medications with elevated blood pressures as defined above may have their medications adjusted; if patients have persistent \[3 episodes\] of high blood pressure despite medication adjustment they will be considered ineligible for study participation; each measured episode should be 24 hours apart), prior history of hypertensive crisis or hypertensive encephalopathy, uncontrolled or clinically significant arrhythmia, grade II or greater peripheral vascular disease or prior history of stroke or transient ischemic attack (TIA); patient must have a pretreatment multi gated acquisition scan (MUGA) scan or echocardiogram with left ventricular ejection fraction (LVEF) above lower limit of normal
• No non-breast malignancy within the past 5 years other than treated squamous or basal cell carcinoma of the skin or CIS of the cervix
• Patients known to be human immunodeficiency virus (HIV) positive are not eligible for the study given their potentially compromised immune systems and increased risk of treatment-related toxicity
• Advanced (T1N1-4/T2-3 N any) invasive cancer in the contralateral breast
• Any known history of cerebrovascular disease including TIA, stroke or subarachnoid hemorrhage
• Patients must not have a non-healing wound or fracture
• Patients with an abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months
• Patients must not have a bleeding diathesis, hereditary of acquired bleeding disorder or coagulopathy
• Patients on therapeutic doses of Coumadin or Lovenox are ineligible to participate in study
• Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment or anticipation of need for major surgical procedure during the course of the study; core biopsy or other minor surgical procedure, for example placement of a vascular access device, are excluded from this requirement
• No known hypersensitivity to any component of bevacizumab

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106-5065, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Trastuzumab; pertuzumab; Docetaxel; Carboplatin; Doxorubicin; Cyclophosphamide; Paclitaxel; Taxes; Bevacizumab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Economics; Health Care Economics and Organizations

Results Point of Contact

• Title: Dr. Paula Silverman
• Organization: Cleveland Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

CTUreferral@UHhospitals.org

1-800-641-2422

Study Officials

• Paula Silverman, MD

  Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: August 16, 2013
• First Posted: October 10, 2013
• Study Start: September 24, 2013
• Primary Completion: November 11, 2016
• Study Completion: March 29, 2017
• Last Updated: March 5, 2019
• Results First Posted: March 5, 2019

Record last verified: 2019-02

Locations

US (1)