A Study to Look at the Combination of Chemotherapy, Trastuzumab and RAD001 in HER2 Positive Breast Cancer

NCT01163929 | Withdrawn Phase 2 DMC

• 1 other identifier: 12186
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The primary objective of this study is to assess whether a combination of chemotherapy, Trastuzumab and RAD001 will result in no evidence of microscopic disease at the time of surgery in 50% of enrolled patients.

Conditions

Breast Cancer

Keywords

breast cancer; HER2 positive; Phase II; RAD001; paclitaxel; trastuzumab; everolimus

Outcome Measures

Primary Outcomes (1)

• assess complete response rate

  To assess the pathological complete response rate (pCR) with of 4 cycles of neoadjuvant Herceptin plus Paclitaxel and Everolimus in patients with operable HER-2 positive breast cancer.

  5 months

Secondary Outcomes (1)

• assess objective/radiological response rate and tolerability

  5 months

Study Arms (1)

paclitaxel, trastuzumab and everolimus

EXPERIMENTAL

Drug: paclitaxel

Interventions

paclitaxel DRUG

Paclitaxel: 80mg/m2 IV TRO 3 hours every 28 days for 4 cycles Trastuzumab: 4mg/kg IV load dose (TRO 90) minutes followed by 2 mg/kg TRO 60 minutes every week for 18 weeks Everolimus: 10mg PO daily 16-18 weeks

Also known as: Taxol, Herception, RAD001

paclitaxel, trastuzumab and everolimus

Eligibility Criteria

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

You may qualify if:

• Female ≥ 18 to 65 years of age
• Histologically proven stage I, II or III adenocarcinoma of breast
• Candidate for adjuvant chemotherapy and Trastuzumab (Tumor size \> 1 cm, T2, T3, T4 and/or clinical N1 or N2)
• HER-2 positive breast cancer (IHC 3+ or FISH ratio of \> 2.0)
• ECOG Performance status 0-2
• No prior chemotherapy or HER-2 targeted therapy for breast cancer
• Not pregnant or breast feeding or adult of reproductive potential using effective birth control methods. If barrier contraceptives are used, these must be continued throughout trial by both sexes. Hormonal contraceptives not acceptable as a sole method of contraception. Women of childbearing potential must have negative urine or serum pregnancy test within 7 days before administration of RAD001
• Adequate bone marrow function: ANC \> 1500/mm3, platelet count \> 100,000/mm3, and hemoglobin \> 11 g/dL
• Adequate kidney function: serum creatinine of \< 1.5mg/dl and/or creatinine clearance of \> 60 mL/min
• Adequate hepatic function: transaminase \< 2 x upper limit of normal and total bilirubin \< 1.5 mg/dL.
• INR ≤2.0 and PTT 1.5 X the upper limit of institution normal range. Oral anticoagulants, eg,warfarin are CYP2C9 substrates and as such, no interaction with RAD001 is expected. Anticoagulation with Coumadin allowed if target INR is ≤2.0 and stable for \> 2 weeks. Anticoagulation with LMWH is allowed.
• Must sign informed consent
• Pretreatment lab values for CBC and CMP performed within 14 days of registration and other baseline studies within 30 days.
• Will have baseline mammogram, bone scan, CT chest and abdomen within 60 days of registration.
• Adequate cardiac function (Cardiac ejection fraction ≥ 50% as measured by echocardiogram or MUGA scan).

You may not qualify if:

• Prior HER-2 targeted therapy for breast cancer
• Metastatic disease
• Uncontrolled intercurrent illness including but not limited to, ongoing or active infection requiring parenteral antibiotics or psychiatric illness/social situations that would limit compliance with study requirements.
• GI tract disease resulting in inability to take oral medication, malabsorption syndrome, a requirement for IV alimentation, prior surgical procedures affecting absorption, uncontrolled inflammatory GI disease eg, Crohn's, ulcerative colitis).
• Current active hepatic or biliary disease (exception of patients with Gilbert's syndrome, asymptomatic gallstones)
• Renal function as measured by creatinine clearance \<30ml/min (ratio to norm \<0.1)
• Pregnant
• Inflammatory breast cancer
• Active cardiac disease, defined as:
• History of uncontrolled or symptomatic angina
• History of arrhythmias requiring medications, or clinically significant, with exception of asymptomatic atrial fibrillation requiring anticoagulation
• Myocardial infarction \< 6 months from study entry
• Uncontrolled or symptomatic congestive heart failure
• Any other cardiac condition, which in opinion of treating physician, would make this protocol unreasonably hazardous for the patient
• History of another primary cancer, with the exception of:

Sponsors & Collaborators

• University of Kansas: lead
• Novartis: collaborator

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Paclitaxel; Everolimus

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; Sirolimus; Macrolides; Lactones

Study Officials

• Priyanka Sharma, MD

  University of Kansas Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: July 14, 2010
• First Posted: July 16, 2010
• Study Start: July 1, 2010
• Primary Completion: March 1, 2012
• Study Completion: March 1, 2012
• Last Updated: October 24, 2012

Record last verified: 2012-10