Trastuzumab With or Without Everolimus in Treating Women With Breast Cancer That Can Be Removed By Surgery

NCT00674414 | Terminated Phase 2

• 4 other identifiers: CDR0000595159FRE-FNCLCC-GEP-04/0606-RAD-HEREUDRACT-2007-004098-24EU-20851
• Study Type: interventional
• Target: 82
• Locations: 1 country
• Sites: 8

Brief Summary

RATIONALE: Monoclonal antibodies, such as trastuzumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. It is not yet known whether giving everolimus together with trastuzumab is more effective than giving trastuzumab alone in treating women with breast cancer. PURPOSE: This randomized phase II trial is studying trastuzumab and everolimus to see how well they work compared to trastuzumab alone before surgery in treating patients with breast cancer that can be removed by surgery.

Conditions

Breast Cancer

Keywords

stage IA breast cancer; stage IB breast cancer; stage II breast cancer; stage IIIA breast cancer; HER2-positive breast cancer

Outcome Measures

Primary Outcomes (1)

• Efficacy as measured by clinical and echographic tumor evaluation

  january 2013

Secondary Outcomes (6)

• Disease-free survival at 3 years

  January 2015

• Pathological response assessed after 6 weeks of treatment

  January 2013

• Clinical response predictive factors

  May 2013

• Rate of pathological complete response (pCR)

  January 2013

• Pharmacogenomics, proteomics, immunohistochemistry (IHC), pharmacokinetics

  december 2013

Study Arms (2)

Arm I

ACTIVE COMPARATOR

Patients receive trastuzumab (Herceptin®) IV once weekly for 6 weeks. Patients then undergo surgery.

Biological: trastuzumab; Procedure: therapeutic conventional surgery

Arm II

EXPERIMENTAL

Patients receive trastuzumab as in arm I and oral everolimus once daily for 6 weeks. Within 24 hours after completing everolimus, patients undergo surgery.

Biological: trastuzumab; Drug: everolimus; Procedure: therapeutic conventional surgery

Interventions

trastuzumab BIOLOGICAL

Trastuzumab (Herceptin®) IV once weekly

Arm I; Arm II

everolimus DRUG

Oral everolimus once daily

Arm II

therapeutic conventional surgery PROCEDURE

Patients undergo surgery

Arm I; Arm II

Eligibility Criteria

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

DISEASE CHARACTERISTICS: * Histologically confirmed diagnosis of invasive breast cancer * Previously untreated disease * Candidate for breast-conserving surgery, as defined by both of the following: * Clinical stage cT1-3, cN0-2 disease * Clinical stage M0 disease (bone scan, chest X-ray, and liver ultrasound required at screening to exclude metastatic disease) * HER2-positive primary tumor, defined as meeting either of the following criteria: * IHC 3+ * IHC 2+ and FISH positive (centralized confirmation) * No inflammatory breast cancer or bilateral breast cancer * Patients who have been treated for cancer of the contralateral breast can be included if there is at least a 5 year time interval from last systemic treatment for breast cancer before randomization into this study * Hormone receptor status not specified PATIENT CHARACTERISTICS: * WHO performance status 0-1 * Menopausal status not specified * WBC ≥ 3.5 x 10\^9/L * ANC ≥ 1.5 x 10\^9/L * Platelet count ≥ 100 x 10\^9/L * Hb ≥ 10 g/dL * Serum bilirubin ≤ 1.5 times upper limit of normal (ULN) * Serum transaminases activity ≤ 2.5 times ULN * Alkaline phosphatase ≤ 2.5 times ULN * Creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 60 mL/min * FEV \> 55% by MUGA or ECHO * Spirometry and DLCO \> 50% of normal * O\_2 saturation \> 88% at rest on room air * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No known hypersensitivity to everolimus, sirolimus, trastuzumab (Herceptin®), or lactulose * No hypercholesterolemia/hypertriglyceridemia ≥ grade 3 * No hypercholesterolemia/hypertriglyceridemia ≥ grade 2 with history of coronary artery disease (despite lipid-lowering treatment if given) * No uncontrolled infection * No other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study, including any of the following: * Uncontrolled hypertension * Congestive cardiac failure * Ventricular arrhythmias * Active ischemic heart disease * Myocardial infarction within the past year * Chronic liver or renal disease * Active gastrointestinal tract ulceration * Severely impaired lung function * No known history of HIV seropositivity * No psychological, familial, sociological, or geographical condition potentially hampering compliance with the study protocol and follow-up schedule * Willing to participate in the biological investigations * Not deprived of liberty or placed under guardianship * Patients must be affiliated to a Social Security System PRIOR CONCURRENT THERAPY: * See Disease Characteristics * More than 30 days (from the screening visit) since prior other investigational drugs * More than 5 days (from randomization) since prior and no concurrent strong inhibitors or inducers of the isoenzyme CYP3A, including any of the following * Rifabutin * Rifampicin * Clarithromycin * Ketoconazole * Itraconazole * Voriconazole * Ritonavir * Telithromycin * No other concurrent anti-cancer treatments such as chemotherapy, immunotherapy/biological response modifiers, endocrine therapy, or radiotherapy

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• UNICANCER: lead

Study Sites (8)

Centre Oscar Lambret

Lille, 59020, France

Location

Centre Leon Berard

Lyon, 69373, France

Location

Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes

Marseille, 13273, France

Location

Centre Regional Rene Gauducheau

Nantes-Saint Herblain, 44805, France

Location

Centre Antoine Lacassagne

Nice, 06189, France

Location

Institut Curie Hopital

Paris, 75248, France

Location

Centre Alexis Vautrin

Vandœuvre-lès-Nancy, 54511, France

Location

Institut Gustave Roussy

Villejuif, F-94805, France

Location

Related Publications (1)

• Campone M, Bachelot T, Treilleux I, Pistilli B, Salleron J, Seegers V, Arnedos M, Loussouarn D, Wang Q, Vanlemmens L, Jimenez M, Rios M, Dieras V, Leroux A, Paintaud G, Rezai K, Andre F, Lion M, Merlin JL. A phase II randomised study of preoperative trastuzumab alone or combined with everolimus in patients with early HER2-positive breast cancer and predictive biomarkers (RADHER trial). Eur J Cancer. 2021 Nov;158:169-180. doi: 10.1016/j.ejca.2021.09.017. Epub 2021 Oct 19.

  PMID: 34678678 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Trastuzumab; Everolimus

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; Sirolimus; Macrolides; Lactones; Organic Chemicals

Study Officials

• Mario Campone, MD

  Centre Regional Rene Gauducheau

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: May 6, 2008
• First Posted: May 7, 2008
• Study Start: April 1, 2008
• Primary Completion: January 1, 2013
• Last Updated: January 18, 2013

Record last verified: 2013-01

Locations

FR (8)